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>>THANK YOU

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FOR JOINING TODAY.

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I AM DR. ANDREA DEPUTY DIRECTOR

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OF THE NIH BRAIN INITIATIVE, AND

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I'M VERY HAPPY TO BE HERE TODAY

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TO INTRODUCE THE SESSION ALONG

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WITH MY COLLEAGUE, DR. JAY

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CHURCHILL.

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IT'S PARTICULARLY APPROPRIATE

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THAT WE ARE SHARING THIS

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RESPONSIBILITY TODAY BECAUSE JAY

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AND I WERE TRAINEES TOGETHER.

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WE WERE POSTDOCS IN THE SAME LAB

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MANY YEARS AGO, TOO MANY THAT I

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WON'T MENTION RIGHT NOW.

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AT ANY RATE, I WOULD LIKE TO

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WELCOME YOU ALL TO THIS YEAR'S

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TRAINEE HIGHLIGHT AWARDS TALKS,

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TRAINEES ARE DEFINED AS HIGH

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SCHOOL, UNDERGRADUATE, GRADUATE

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AND MEDICAL SCHOOL STUDENTS AS

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WELL AS POSTDOCTORAL FELLOWS AND

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MEDICAL RESIDENTS.

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THIS YEAR WE RECEIVED OVER 120

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HIGHLIGHTED THE TRAINEES'

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SPECIFIC CONTRIBUTIONS TO THEIR

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MENTOR'S BROADER BRAIN AWARDS.

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THE REVIEW TEAM WORKED REALLY

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HARD ALONG WITH THE MEETING

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PLANNING COMMITTEE AND SELECTED

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THE TOP 30 FINALISTS TO PRESENT

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FLASH TALKS TODAY DURING THIS

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YEAR'S MEETING PROGRAM.

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ALONG WITH AN INTERACTIVE

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VIRTUAL POSTER.

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AN ADDITIONAL 30 HONORABLE

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MENTION RECIPIENTS WERE SELECTED

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TO DISPLAY THEIR RESEARCH IN

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THIS YEAR'S POSTER GALLERY AS

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WELL.

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>> AS ANDREA SAID, WELCOME
TO

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THE SESSION.

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WE'RE REALLY, REALLY HAPPY TO BE

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HERE AND WE ARE POSITIVE THAT

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YOU'RE GOING TO HEAR SOME REALLY

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FANTASTIC SCIENCE FROM PROMISING

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INVESTIGATORS.

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SO AS ANDREA MENTIONED, MY NAME

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IS JAY CHURCHILL AND I SERVE AS

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THE CO-LEAD FOR THE TRAINING,

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INCLUSION AND EQUITY TEAM FOR

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THE BRAIN INITIATIVE AT THE NIH.

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AND REALLY IN A BIT OF A

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SELF-SERVING POSITION, I'LL SAY

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IF YOU HAVE INTEREST IN FUNDING

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OPPORTUNITIES, PARTICULARLY AT

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YOUR CAREER STAGE, PLEASE,

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PLEASE, PLEASE REACH OUT TO US.

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WE ARE PUBLIC SERVANTS, WE ARE

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HERE TO HELP YOU, BUT WE CAN'T

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HELP, WE CAN'T PROVIDE THAT

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GUIDANCE IF YOU DON'T REACH OUT

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TO US FIRST AND I'LL PUT MY

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EMAIL INFORMATION IN THE CHAT

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BOX FOR PEOPLE AND PLEASE SPREAD

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THIS AROUND.

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SO FOR TODAY, AWARD RECIPIENTS

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WERE SELECTED THROUGH A PROCESS

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BASED ON MULTIPLE FACTORS.

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SOME OF THESE CRITERIA INCLUDE

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THINGS SUCH AS THE SCIENTIFIC

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FOCUS OF THE WORK, WITH

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PRIORITIZATION FOR NULLIFYING

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THESE OR FUTURE RESEARCH

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DIRECTIONS IN AREAS OF HIGH

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PRIORITY FOR THE NIH BRAIN

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INITIATIVE.

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00:02:23,680 --> 00:02:26,080
ANOTHER FACTOR INCLUDES HOW THE

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00:02:26,080 --> 00:02:27,680
TRAINEES' RESEARCH CONTRIBUTES

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TO THE LARGER BRAIN-RELATED

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RESEARCH EFFORT WITH

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CONSIDERATION AS TO WHETHER IT

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INTEGRATES OR COMPLEMENTS

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ONGOING EFFORTS WITHIN THE LAB,

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AND IN PARTICULAR, PROJECTS

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SUPPORTED DIRECTLY THROUGH THE

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BRAIN INITIATIVE.

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ANOTHER FACTOR IS IF THE

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APPROACH PROVIDES GREAT EXAMPLES

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OF INCLUSION STRATEGIES THAT

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ADVANCE THE SCIENTIFIC AND

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TECHNICAL MERIT OF THE RESEARCH

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THROUGH ENHANCED INCLUSIVITY.

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THERE ARE MANY REALLY GREAT

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PROJECTS SUBMIT BID TRAINEES

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ACROSS THE RESEARCH TRAINING

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PIPELINE, UNFORTUNATELY WE CAN

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ONLY SELECT A SMALL NUMBER THAT

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YOU'LL HEAR ABOUT TODAY.

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WHAT YOU'LL HEAR SHORTLY ARE

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RESEARCH HIGHLIGHTS FROM 15 OF

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THESE TRAINEES.

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YOU SEE A LOT OF THESE REALLY

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GREAT SMILING FACES IN FRONT OF

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YOU NOW.

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THERE ARE 15 MORE OF THEM BEING

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PRESENTED SIMULTANEOUSLY IN

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ANOTHER PANEL.

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WE ARE ONLY -- WE GOT THE BEST

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15 HERE, THOUGH.

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DON'T TELL ANYBODY ELSE THAT.

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WHAT WE ASK YOU AS FAR AS A

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MATTER OF PROCESS IS THAT IF YOU

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HAVE QUESTIONS FOR THESE PEOPLE

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PLEASE USE THE QUESTION AND

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ANSWER BOX.

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AND IF YOU HAVE A SPECIFIC

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QUESTION FOR ONE OF THESE,

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PLEASE MENTION THEIR NAME AS

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WELL SO WE CAN DIRECT THE

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QUESTION TO THEM.

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ANDREA AND I WILL ATTEMPT TO

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RELAY THESE QUESTIONS TO THE

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PRESENTERS AFTER WE HAVE

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FINISHED HEARING FROM ALL 15 OF

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THESE REALLY GREAT

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INVESTIGATORS.

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SO AGAIN, JOIN US IN WELCOMING

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OUR TRAINEE HIGHLIGHT AWARD

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PRESENTERS.

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>> HELLO, MY NAME IS
DESIREE

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JOHNSON, RESEARCH ASSISTANT AT

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THE UNIVERSITY OF CALIFORNIA

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SAN DIEGO.

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OUR BRAIN INITIATIVE FUNDED

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RESEARCH AIMS TO IMPROVE DRUG

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TARGETING IN THE NERVOUS SYSTEM

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USING LIGHT.

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WE DEVELOP PHOTO ACTIVATABLE OR

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CAGED MOLECULES ADMINISTERED IN

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AN BE INACTIVE CAGED FORM AND

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LATER ACTIVATED WITH LIGHT.

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PHOTO ACTIVATION OFFERS SPATIAL

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AND TEMPORAL PRECISION, AS WELL

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AS A ROBUST STIMULUS RESPONSE

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RELATIONSHIP WHICH CREATES

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OPPORTUNITIES TO QUANTIFY DRUG

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RESPONSES IN NEW WAYS.

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THIS IS NOT ONLY USEFUL FOR

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MECHANISTIC INVESTIGATIONS INTO

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DRUG ACTION BUT ALSO HAS

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POTENTIAL APPLICATIONS IN

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BIOMEDICINE.

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BY RESTRICTING ILLUMINATION TO A

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SPECIFIC REGION OF THE BODY OR

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NERVOUS SYSTEM, PHOTO ACTIVATION

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OF OPIOID DRUGS COULD YIELD

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TARGET PAIN RELIEF WHILE

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MINIMIZING SIDE EFFECTS SUCH AS

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RESPIRATORY DEPRESSION AND

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ADDICTION.

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PREVIOUSLY, CAGED COMPOUNDS HAVE

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BEEN PRIMARILY USED IN EX VIVO

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PREPARATION SUCH AS BRAIN

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SLICES, BUT WE ARE MOVING PHOTO

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PHARMACOLOGY IN VIVO TO STUDY

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HOW DRUGS AND NEUROMODULATORS

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INFLUENCE ANIMAL BEHAVIOR.

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YOU MAY HAVE ALREADY SEEN MY

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OTHER POSTER DESCRIBING A CAGED

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VAIR YABT OF       

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VARIANT OF THE SMALL MOLECULE

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DRUG OXYMORPHONE THROUGH A

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FIBEROPTIC CABLE IMPRINTED IN

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THE MOUSE BRAIN.

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I DESCRIBE OUR VALIDATION OF A

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CAGE DERIVATIVE OF THE MU OPIOID

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RECEPTOR AGONIST THAT CAN BE

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INFUSED INTO THE RODENT BRAIN

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THROUGH A CANNULA.

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AND THEN PHOTO ACTIVATED WITH UV

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LIGHT ACCORDING TO THE REACTION

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SHOWN HERE.

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WE THINK THAT THIS TOOL WILL BE

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USEFUL TO STUDY HOW

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OPIOID-SENSITIVE CIRCUITS

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INFLUENCE BEHAVIOR.

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AFTER IN VITRO AND EX VIVO

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VALIDATION IN BRAIN SLICES TO

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VALIDATE IN VIVO, I IMPLANTED

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CANNULAS JUST ABOVE THE VENTRAL

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TEGMENTAL AREA WHERE OPIOID

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SIGNALING ACTIVATES DOPAMINE

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NEURONS TO DRIVE BEHAVIORAL

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REINFORCEMENT AND ENHANCE

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LOCOMOTION.

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I LOCALLY ADMINISTERED AND

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SUBSEQUENTLY PHOTO ACTIVATED AT

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THE SAME TIME 15 MINUTES LATER

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USING A 375 NANOMETER LASER

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WHILE MICE WERE EXPLORING IN

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OPEN FIELDS.

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DELIVERY OF LIGHT CAUSED A MERE

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INSTANTANEOUS INCREASE IN

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LOCOMOTION, REPRESENTED HERE AS

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VELOCITY THAT WAS BLOCKED BY THE

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OPIOID RECEPTOR ANTAGONIST

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NALOXONE.

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QUANTIFIED ON THE RIGHT, YOU CAN

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SEE NALOXONE RETURN DISTANCE

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TRAVELED TO LEVELS SIMILAR TO

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VEHICLE AND NO LIGHT CONDITIONS.

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TAKEN TOGETHER, OUR DATA

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DEMONSTRATE THAT IN VIVO

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UNCAGING IS A VIABLE APPROACH TO

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MANIPULATING NEURAL CIRCUIT AND

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BEHAVIOR WITH TEMPORAL PRECISION

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ALL IN A TIME SCALE OF SECONDS.

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WE ARE APPLYING THIS APPROACH TO

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VARIOUS NEUROPEPTIDE SYSTEMS AND

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TO OTHER INTERESTING THERAPEUTIC

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DRUGS SUCH AS KETAMINE.

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WE ARE ALWAYS INTERESTED IN

224
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COLLABORATION SO IF PHOTO

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PHARMACOLOGY COULD ADVANCE YOUR

226
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RESEARCH PROGRAM, PLEASE REACH

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OUT.

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>> HELLO, EVERYONE.

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I'M A POSTDOCTORAL SCHOLAR AT

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UNIVERSITY OF CALIFORNIA

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BERKELEY.

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PERCEPTION IS WIDELY

233
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MISCONCEPTUALIZED AS FAITHFUL

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REPRESENTATION OF SENSORY

235
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INFORMATION.

236
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BUT IF THIS WERE THE CASE, WE

237
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WOULD NOT BE SUSCEPTIBLE TO

238
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ILLUSIONS.

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ILLUSIONS ARISE WHEN THE BRAIN'S

240
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INFERRED PERCEPTUAL OBJECT DOES

241
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NOT MATCH THE SENSORY EVIDENCE.

242
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HERE, WE UTILIZE CONTOURS TO

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DETERMINE THE PERCEPTUAL

244
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INFERENCE IN THE MOUSE VISUAL

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CORTEX.

246
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WE USE TWO PHOTO SCOPE TO

247
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MEASURE VISUAL RESPONSES FROM

248
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THOUSANDS OF NEURONS ACROSS SIX

249
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SPATIAL AREAS SIMULTANEOUSLY.

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WE STARTED BY COMPARING THE

251
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ACTIVITY EVOKED BY ILLUSORY --

252
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BY ROTATED CONTROLS.

253
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THE PAIR OF ROTATED CONTROL

254
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IMAGES INDICATED RC1 AND RC2 IN

255
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THE FIGURE WAS DESIGNED TO MATCH

256
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THE SUM OF PARTS IN THE PAIR OF

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ILLUSORY CONTOUR IMAGES, IC1 AND

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IC2.

259
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THEREFORE, IF SENSORY

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REPRESENTATION IS FAITHFUL, THE

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SUM OF ACTIVITY EVOKED BY

262
00:08:21,200 --> 00:08:24,240
ILLUSORY CONTOURS WOULD BE THE

263
00:08:24,240 --> 00:08:25,680
SAME AS THE SUM OF ACTIVITY

264
00:08:25,680 --> 00:08:29,920
EVOKED BY ROTATED CONTROLS.

265
00:08:29,920 --> 00:08:30,960
TO OUR INITIAL SURPRISE,

266
00:08:30,960 --> 00:08:32,800
HOWEVER, WE DID NOT SEE

267
00:08:32,800 --> 00:08:35,280
POPULATION AVERAGE DIFFERENCES

268
00:08:35,280 --> 00:08:38,560
IN ANY OF THE NEOCORTICAL VISUAL

269
00:08:38,560 --> 00:08:40,120
AREAS BETWEEN THE ACTIVITY

270
00:08:40,120 --> 00:08:42,080
EVOKED BY ILLUSORY CONTOURS

271
00:08:42,080 --> 00:08:46,880
VERSUS ROTATED CONTROLS.

272
00:08:46,880 --> 00:08:47,880
HOWEVER, THIS RESULT DOES NOT

273
00:08:47,880 --> 00:08:48,880
INDICATE THAT NONE OF THESE

274
00:08:48,880 --> 00:08:55,920
VISUAL AREAS COMPUTE PERCEPTUALR

275
00:08:55,920 --> 00:08:56,440
INFERENCE.

276
00:08:56,440 --> 00:08:57,760
THAT IS BECAUSE POPULATION

277
00:08:57,760 --> 00:08:59,080
AVERAGE DIFFERENCE IS A

278
00:08:59,080 --> 00:09:00,600
SUFFICIENT BUT NOT A NECESSARY

279
00:09:00,600 --> 00:09:02,440
INDICATOR OF PERCEPTUAL

280
00:09:02,440 --> 00:09:03,240
INFERENCE.

281
00:09:03,240 --> 00:09:06,080
AS SUCH, WE TOOK AN ALTERNATIVE

282
00:09:06,080 --> 00:09:07,720
APPROACH AND USED MACHINE

283
00:09:07,720 --> 00:09:11,880
LEARNING DECODING TO ASSESS

284
00:09:11,880 --> 00:09:15,040
NEURAL ACTIVITY PATTERNS.

285
00:09:15,040 --> 00:09:17,760
SPECIFICALLY, WE USE THE SUPPORT

286
00:09:17,760 --> 00:09:19,520
VECTOR MACHINE DECODER WITH A

287
00:09:19,520 --> 00:09:23,040
LINEAR COLONEL.

288
00:09:23,040 --> 00:09:25,440
 KERNEL.

289
00:09:25,440 --> 00:09:29,160
ACTIVELY DEPICTED FROM VISUAL

290
00:09:29,160 --> 00:09:29,480
RESPONSES.

291
00:09:29,480 --> 00:09:32,120
NOW TO ASSESS WHETHER THE

292
00:09:32,120 --> 00:09:33,640
ILLUSORY CONTOUR WAS REPRESENTED

293
00:09:33,640 --> 00:09:36,040
IN EACH VISUAL AREA, WE DESIGNED

294
00:09:36,040 --> 00:09:38,880
A REAL EDGE STIMULUS THAT

295
00:09:38,880 --> 00:09:43,080
INCLUDES A T SHAPE DENOTED

296
00:09:43,080 --> 00:09:46,560
RET1 AND RE T2 IN THE FIGURE.

297
00:09:46,560 --> 00:09:49,280
RET1 STIMULUS HAS EQUAL OVERLAP

298
00:09:49,280 --> 00:09:54,760
WITH IC1 AND RC1.

299
00:09:54,760 --> 00:09:57,000
THEREFORE, RET1 ACTIVITY WILL BE

300
00:09:57,000 --> 00:10:01,560
EQUALLY LIKELY TO BE DECOATED  S

301
00:10:01,560 --> 00:10:04,800
IC1 OR RC1, IF AND ONLY IF

302
00:10:04,800 --> 00:10:07,000
REPRESENTATION WAS FAITHFUL.

303
00:10:07,000 --> 00:10:09,200
USING THIS APPROACH, WE FOUND

304
00:10:09,200 --> 00:10:11,720
THAT THE INFERRED REPRESENTATION

305
00:10:11,720 --> 00:10:14,000
OF THE ILLUSORY CONTOUR IS

306
00:10:14,000 --> 00:10:18,920
PRESENT IN LAYER 23 OF V1, RM

307
00:10:18,920 --> 00:10:21,200
AND RL, INDICATING FUNCTIONAL

308
00:10:21,200 --> 00:10:22,520
SPECIALIZATION OF HIGHER VISUAL

309
00:10:22,520 --> 00:10:23,960
AREAS.

310
00:10:23,960 --> 00:10:26,480
ON THE OTHER HAND,

311
00:10:26,480 --> 00:10:29,760
REPRESENTATION IN LAYER FOUR OF

312
00:10:29,760 --> 00:10:32,360
V1 WAS FAITHFUL, SUGGESTING THAT

313
00:10:32,360 --> 00:10:33,240
PERCEPTUAL INFERENCE EMERGES

314
00:10:33,240 --> 00:10:37,200
ALONG THE VISUAL HIERARCHY.

315
00:10:37,200 --> 00:10:38,280
ONGOING EXPERIMENTS AIMED TO

316
00:10:38,280 --> 00:10:40,360
DETERMINE THE RECURRENT

317
00:10:40,360 --> 00:10:42,440
EXCITATORY MECHANISMS BY WHICH

318
00:10:42,440 --> 00:10:43,880
ILLUSORY CONTOUR REPRESENTATION

319
00:10:43,880 --> 00:10:46,400
ARISES.

320
00:10:46,400 --> 00:10:51,960
WE USE OPT GENETICS TO

321
00:10:51,960 --> 00:10:53,600
SELECTIVELY STIMULATE NEURONS OF

322
00:10:53,600 --> 00:10:54,800
INTEREST.

323
00:10:54,800 --> 00:10:57,320
WHEN WE STIMULATED NEURONS THAT

324
00:10:57,320 --> 00:10:59,280
SELECTIVELY RESPOND TO THE

325
00:10:59,280 --> 00:11:00,480
EMERGENT PROPERTIES OF THE

326
00:11:00,480 --> 00:11:03,360
ILLUSORY CONTOUR, IT RECREATED

327
00:11:03,360 --> 00:11:05,960
THE NEURAL ACTIVITY PATTERN

328
00:11:05,960 --> 00:11:07,800
EVOKED BY THE ILLUSORY CONTOUR

329
00:11:07,800 --> 00:11:08,000
IMAGE.

330
00:11:08,000 --> 00:11:11,640
IN OTHER WORDS, HOLE GRAPHIC

331
00:11:11,640 --> 00:11:17,120
STIMULATION OF I  ILLUSORY

332
00:11:17,120 --> 00:11:19,920
CONTOURING DECODERS -- IN LAYER

333
00:11:19,920 --> 00:11:22,040
23 OF V1 WAS SUFFICIENT TO DRIVE

334
00:11:22,040 --> 00:11:23,320
THE NETWORK TO PATTERN

335
00:11:23,320 --> 00:11:23,760
COMPLETION.

336
00:11:23,760 --> 00:11:25,640
IF YOU'RE INTERESTED IN DETAILS,

337
00:11:25,640 --> 00:11:28,080
PLEASE VISIT MY POSTER, NUMBER

338
00:11:28,080 --> 00:11:29,120
825.

339
00:11:29,120 --> 00:11:30,560
THANK YOU VERY MUCH FOR YOUR

340
00:11:30,560 --> 00:11:31,320
ATTENTION.

341
00:11:31,320 --> 00:11:33,760
>> HI, EVERYONE.

342
00:11:33,760 --> 00:11:36,360
I'M A THIRD YEAR PH.D. STUDENT

343
00:11:36,360 --> 00:11:39,640
AT MIT AND I STUDIED THE

344
00:11:39,640 --> 00:11:40,840
ORGANIZATION OF THE SYNAPTIC

345
00:11:40,840 --> 00:11:42,160
MOLECULAR NETWORK.

346
00:11:42,160 --> 00:11:43,680
THIS IS A COMPLEX SYSTEM OF

347
00:11:43,680 --> 00:11:46,080
HUNDREDS OF PROTEIN, EVEN MORE

348
00:11:46,080 --> 00:11:46,720
INTERACTIONS COMPARTMENTALIZED

349
00:11:46,720 --> 00:11:47,840
TO THE SYNAPTIC SITES.

350
00:11:47,840 --> 00:11:49,040
THE SYSTEM IS INTERESTING

351
00:11:49,040 --> 00:11:51,320
BECAUSE IT IS ESSENTIALLY THE

352
00:11:51,320 --> 00:11:54,080
HARDWARE OF WHICH RUNS THE

353
00:11:54,080 --> 00:11:55,600
COMPLEX COMPUTATION OF EACH

354
00:11:55,600 --> 00:11:56,600
INDIVIDUAL SYNAPSE.

355
00:11:56,600 --> 00:11:58,000
RESPONSE TO ACTIVITY CHEMICAL

356
00:11:58,000 --> 00:12:00,120
AND GENETIC HISTORIES LEADING TO

357
00:12:00,120 --> 00:12:01,640
PLASTICITY AND META PLASTICITY.

358
00:12:01,640 --> 00:12:05,240
I STUDIED THE NETWORK -- I WANT

359
00:12:05,240 --> 00:12:06,320
TO FIRST MEASURE THE

360
00:12:06,320 --> 00:12:09,080
DISTRIBUTION OF SYNAPSES IN HIGH

361
00:12:09,080 --> 00:12:10,040
DIMENSIONAL COMPOSITION SPACE

362
00:12:10,040 --> 00:12:11,480
AND TWO, FIGURE OUT THE RULES

363
00:12:11,480 --> 00:12:13,000
THAT GOVERN THIS DISTRIBUTION

364
00:12:13,000 --> 00:12:17,280
AND THE PATHS THAT SYNAPSES TAKE

365
00:12:17,280 --> 00:12:18,480
IN THAT SPACE.

366
00:12:18,480 --> 00:12:20,000
TO ACHIEVE THE FORMER, I NEED A

367
00:12:20,000 --> 00:12:21,520
WAY TO MEASURE MULTIPLE PROTEINS

368
00:12:21,520 --> 00:12:22,720
IN MANY INDIVIDUAL SYNAPSES.

369
00:12:22,720 --> 00:12:24,400
I DO THAT USING PRISSMM.

370
00:12:24,400 --> 00:12:27,680
A HIGH THROUGHPUT QUANTITATIVE

371
00:12:27,680 --> 00:12:29,200
MULTIPLEXED IMAGING TECHNIQUE

372
00:12:29,200 --> 00:12:30,480
DEVELOPED IN THE LAB THAT RELIES

373
00:12:30,480 --> 00:12:33,680
ON FLUORESCENT PROBE EXCHANGE ON

374
00:12:33,680 --> 00:12:34,440
BARCODED ANTIBODIES.

375
00:12:34,440 --> 00:12:36,200
THERE IS ALSO SUCH AN EXPERIMENT

376
00:12:36,200 --> 00:12:38,160
SEEN IN THE TOP RIGHT ARE

377
00:12:38,160 --> 00:12:39,800
SEQUENTIAL IMAGES OF THE SAME

378
00:12:39,800 --> 00:12:41,000
NEURONAL CULTURE, EACH TIME

379
00:12:41,000 --> 00:12:43,640
LIGHTING UP A DIFFERENT PROTEIN.

380
00:12:43,640 --> 00:12:46,800
I CAN AUTOMATICALLY SEGMENT

381
00:12:46,800 --> 00:12:47,880
INDIVIDUAL SYNAPTIC -- USING

382
00:12:47,880 --> 00:12:49,760
CELL PROFILER AND QUANTIFY THEM

383
00:12:49,760 --> 00:12:51,720
ACROSS CHANNELS, GETTING

384
00:12:51,720 --> 00:12:53,800
MULTI-PROTEIN MEASUREMENTS FOR

385
00:12:53,800 --> 00:12:56,000
MILLIONS OF INDIVIDUAL SYNAPSES.

386
00:12:56,000 --> 00:13:01,880
I THEN USE BAYESIAN NETWORK

387
00:13:01,880 --> 00:13:04,520
EVIDENCE FROM THIS DISTRIBUTION.

388
00:13:04,520 --> 00:13:06,280
BAYESIAN NETWORK INFOR INSTANCE

389
00:13:06,280 --> 00:13:08,240
ALLOWS ONE TO FACTOR THIS HIGH

390
00:13:08,240 --> 00:13:09,320
DIMENSIONAL DATA INTO SINGLE

391
00:13:09,320 --> 00:13:12,600
VARIABLE CONDITION OF THE

392
00:13:12,600 --> 00:13:13,480
DISTRIBUTIONS SUCH AS THE ONE ON

393
00:13:13,480 --> 00:13:15,240
THE BOTTOM RIGHT.

394
00:13:15,240 --> 00:13:17,400
FROM ONE TO ANOTHER IMPLIES THAT

395
00:13:17,400 --> 00:13:19,280
THE DISTRIBUTION OF THE CHANNEL

396
00:13:19,280 --> 00:13:20,480
DEPENDS ON THE LEVELS OF THE

397
00:13:20,480 --> 00:13:20,920
PARENT.

398
00:13:20,920 --> 00:13:23,120
MORE INTERESTINGLY, LACK OF AN

399
00:13:23,120 --> 00:13:25,200
EDGE INDICATES THAT EVEN THOUGH

400
00:13:25,200 --> 00:13:26,520
TWO NODES MAY BE TIGHTLY

401
00:13:26,520 --> 00:13:27,480
CORRELATED, ANY CONNECTION

402
00:13:27,480 --> 00:13:28,880
BETWEEN THEM IS EXPLAINED BY

403
00:13:28,880 --> 00:13:30,760
OTHER VARIABLES.

404
00:13:30,760 --> 00:13:34,080
THE RESULTING MODEL GIVES --

405
00:13:34,080 --> 00:13:35,120
PREDICTIONS ABOUT DOWNSTREAM

406
00:13:35,120 --> 00:13:36,280
EFFECTS OF DETECTING CERTAIN

407
00:13:36,280 --> 00:13:36,560
NODES.

408
00:13:36,560 --> 00:13:41,720
FOR EXAMPLE, THE ACTIN 3 CHAIN

409
00:13:41,720 --> 00:13:44,520
PREDICTS THAT FIRST DIRECT

410
00:13:44,520 --> 00:13:45,640
PRESERVATION OF SHANK 3 SHOULD

411
00:13:45,640 --> 00:13:50,760
AFFECT ONLY SHANK 3.

412
00:13:50,760 --> 00:13:52,640
PSD95 SHOULD AFFECT BOTH

413
00:13:52,640 --> 00:13:54,040
PSD95 AND SHANK 3 AND ACTIN

414
00:13:54,040 --> 00:13:54,840
SHOULD AFFECT ALL THREE.

415
00:13:54,840 --> 00:13:57,360
IN ADDITION, SINCE THE EFFECT ON

416
00:13:57,360 --> 00:14:00,400
SHANK 3 SHOULD BE MEDIATED

417
00:14:00,400 --> 00:14:02,840
MOSTLY BY CHANGING PSD95 LEVELS,

418
00:14:02,840 --> 00:14:03,960
WHEN THE CONTROL FOR THAT, THE

419
00:14:03,960 --> 00:14:05,560
EFFECT OF CHANGING ACTIVE ON

420
00:14:05,560 --> 00:14:06,320
SHANK 3 SHOULD WEAKEN.

421
00:14:06,320 --> 00:14:08,400
THIS IS EXACTLY WHAT I OBSERVED

422
00:14:08,400 --> 00:14:09,600
WHEN TESTING THESE

423
00:14:09,600 --> 00:14:10,800
PRESERVATIONS.

424
00:14:10,800 --> 00:14:13,320
FINALLY, IN COLLABORATION

425
00:14:13,320 --> 00:14:14,720
WITH -- PSYCHIATRIC RESEARCH AT

426
00:14:14,720 --> 00:14:16,720
THE BROAD INSTITUTE, HOW THE

427
00:14:16,720 --> 00:14:18,560
MOLECULAR SYSTEM AS A WHOLE IS

428
00:14:18,560 --> 00:14:21,520
AFFECTED BY PERTURBING DIFFERENT

429
00:14:21,520 --> 00:14:23,600
GENES ASSOCIATED WITH AUTISM AND

430
00:14:23,600 --> 00:14:25,000
SCHIZOPHRENIA.

431
00:14:25,000 --> 00:14:26,200
WE OBSERVE ALTHOUGH KNOCK DOWN

432
00:14:26,200 --> 00:14:27,760
OF DIFFERENT GENES HAVE VARYING

433
00:14:27,760 --> 00:14:30,720
EFFECTS ON THE SYNAPTIC PROTEINS

434
00:14:30,720 --> 00:14:32,000
THEMSELVES, SOME NETWORK EDGES

435
00:14:32,000 --> 00:14:33,120
WERE CONSISTENTLY STRENGTHENED

436
00:14:33,120 --> 00:14:35,280
OR WEAKENED BUT ALL TREATMENTS

437
00:14:35,280 --> 00:14:38,440
AS SHOWN IN COLORS IN THE GRAPH

438
00:14:38,440 --> 00:14:39,680
ON THE RIGHT.

439
00:14:39,680 --> 00:14:42,640
THESE PHENOTYPES MAY PROVIDE THE

440
00:14:42,640 --> 00:14:44,160
CLUE -- BY WHICH DIFFERENT

441
00:14:44,160 --> 00:14:45,880
AUTISM AND

442
00:14:45,880 --> 00:14:47,960
SCHIZOPHRENIA-ASSOCIATED

443
00:14:47,960 --> 00:14:49,320
MUTATIONS GIVE RISE TO SIMILAR

444
00:14:49,320 --> 00:14:49,560
SYMPTOMS.

445
00:14:49,560 --> 00:14:51,280
I AM CURRENTLY EXPANDING THIS

446
00:14:51,280 --> 00:14:54,120
COMBINED EXPERIMENTAL AND

447
00:14:54,120 --> 00:14:54,880
COMPUTATIONAL METHODOLOGY IN

448
00:14:54,880 --> 00:14:56,400
SEVERAL DIRECTIONS.

449
00:14:56,400 --> 00:14:57,840
COMBINING WITH IMAGING TO

450
00:14:57,840 --> 00:14:59,240
INTEGRATE SYNAPTIC ACTIVITY

451
00:14:59,240 --> 00:15:02,200
MEASUREMENTS INTO THIS PROTEIN

452
00:15:02,200 --> 00:15:02,840
NETWORK.

453
00:15:02,840 --> 00:15:04,600
DEVELOPING A FRAMEWORK FOR

454
00:15:04,600 --> 00:15:06,000
THE -- USING PRISSMM, AND

455
00:15:06,000 --> 00:15:08,040
APPLYING THE METHOD TO

456
00:15:08,040 --> 00:15:09,440
CHARACTERIZE DOWNSTREAM

457
00:15:09,440 --> 00:15:11,200
BIOCHEMICAL EFFECTS OF

458
00:15:11,200 --> 00:15:11,760
PSYCHIATRIC DRUGS.

459
00:15:11,760 --> 00:15:13,600
I HOPE THAT I PROMPTED AT LEAST

460
00:15:13,600 --> 00:15:15,280
SOME OF YOU TO THINK ABOUT THIS

461
00:15:15,280 --> 00:15:17,080
NEW KIND OF DATA MODALITY AND I

462
00:15:17,080 --> 00:15:18,600
WOULD LOVE TO DISCUSS MORE IN

463
00:15:18,600 --> 00:15:19,280
DEPTH AT MY POSTER.

464
00:15:19,280 --> 00:15:26,960
THANK YOU.

465
00:15:26,960 --> 00:15:29,560
>> HELLO, BAYLOR COLLEGE
OF

466
00:15:29,560 --> 00:15:30,440
MEDICINE, HOUSTON, TEXAS.

467
00:15:30,440 --> 00:15:31,520
I'M VERY EXCITED TO DISCUSS WITH

468
00:15:31,520 --> 00:15:36,640
YOU SOME NEW GENETICALLY ENCODED

469
00:15:36,640 --> 00:15:39,040
GEVIs FOR LONG TERM PHOTON

470
00:15:39,040 --> 00:15:42,800
IMAGES.

471
00:15:42,800 --> 00:15:43,760
GEVI -- THROUGH CHANGES IN THEIR

472
00:15:43,760 --> 00:15:44,080
FLUORESCENCE.

473
00:15:44,080 --> 00:15:45,960
THIS CLASS OF SENSOR HAS MANY

474
00:15:45,960 --> 00:15:48,600
ADVANTAGES OVER OTHER SENSING

475
00:15:48,600 --> 00:15:50,880
TECHNIQUES SUCH AS

476
00:15:50,880 --> 00:15:52,480
ELECTROPHYSIOLOGY, MICRO ARRAYS

477
00:15:52,480 --> 00:15:54,520
AND CALCIUM IMAGING.

478
00:15:54,520 --> 00:15:56,040
GEVIs ARE RELATIVELY

479
00:15:56,040 --> 00:15:57,880
NONINVASIVE USING ONLY LIGHT TO

480
00:15:57,880 --> 00:15:59,640
RECORD VOLTAGE DYNAMICS INSTEAD

481
00:15:59,640 --> 00:16:00,760
OF ELECTRODES OR IMPLANTS.

482
00:16:00,760 --> 00:16:02,800
THEY CAN ALSO BE CELL

483
00:16:02,800 --> 00:16:03,760
TYPE-SPECIFIC WHEN EXPRESSED

484
00:16:03,760 --> 00:16:05,640
USING A CELL-TYPE SPECIFIC

485
00:16:05,640 --> 00:16:08,600
PROMOTER.

486
00:16:08,600 --> 00:16:09,800
GEVIs CAN -- RESOLUTION AND

487
00:16:09,800 --> 00:16:12,080
ARE EVEN ABLE TO DETECT

488
00:16:12,080 --> 00:16:14,280
INDIVIDUAL ACTION POTENTIALS IN

489
00:16:14,280 --> 00:16:16,240
FAST WAVE -- FINALLY, GEVIs

490
00:16:16,240 --> 00:16:18,560
CAN HAVE HIGHER SPEACIAL

491
00:16:18,560 --> 00:16:21,240
RESOLUTION BY FACILITATING --

492
00:16:21,240 --> 00:16:24,560
THESE ARE JUST A FEW VAMS OF THE

493
00:16:24,560 --> 00:16:25,880
AGAIN BEN FITS.

494
00:16:25,880 --> 00:16:26,680
WHILE GREAT STRIDES HAVE BEEN

495
00:16:26,680 --> 00:16:29,280
MADE TO IMPROVE THE AVAILABLE

496
00:16:29,280 --> 00:16:32,760
TOOLBOX OF GEVIs, MANY

497
00:16:32,760 --> 00:16:35,280
SCHEDULE WITH PERFORMANCE UNDER

498
00:16:35,280 --> 00:16:36,480
PHOTON MICROSCOPY, A METHOD OF

499
00:16:36,480 --> 00:16:39,560
CHOICE FOR DEEP TISSUE IMAGING.

500
00:16:39,560 --> 00:16:41,520
MANY OF THESE SENSORS SUFFER

501
00:16:41,520 --> 00:16:42,600
FROM PHOTO BLEACHING WHICH CAN

502
00:16:42,600 --> 00:16:45,880
LIMIT THE LENGTH OF   OF CONTINS

503
00:16:45,880 --> 00:16:50,920
RECORDING DURING BEHAVIOR ASSAY

504
00:16:50,920 --> 00:16:52,040
AND -- POTENTIAL DYNAMICS.

505
00:16:52,040 --> 00:16:53,880
COUPLE THIS WITH THE RELATIVELY

506
00:16:53,880 --> 00:16:55,280
DIM PHENOTYPE RESULTS AND

507
00:16:55,280 --> 00:16:56,720
DIFFERENCES IN USING --

508
00:16:56,720 --> 00:16:58,680
DIFFICULTIES IN USING TWO PHOTON

509
00:16:58,680 --> 00:17:00,320
IMAGING IN DEEPER LAYERS OF THE

510
00:17:00,320 --> 00:17:02,960
BRAIN FOR LONG PERIODS OF TIME.

511
00:17:02,960 --> 00:17:04,840
THUS WE SET OUT TO DESIGN A

512
00:17:04,840 --> 00:17:08,040
SENSOR THAT HAS IMPROVED OF

513
00:17:08,040 --> 00:17:09,400
COURSE THROUGH PHOTON PHOTO

514
00:17:09,400 --> 00:17:10,960
STABILITY, BRIGHTNESS AND

515
00:17:10,960 --> 00:17:12,160
SENSITIVITY TO ACTION

516
00:17:12,160 --> 00:17:12,440
POTENTIALS.

517
00:17:12,440 --> 00:17:14,560
WE KNEW THAT LARGE LEAPS IN

518
00:17:14,560 --> 00:17:16,200
SENSOR DESIGN COULD ONLY BE

519
00:17:16,200 --> 00:17:18,400
ACHIEVED USING A HIGH THROUGH

520
00:17:18,400 --> 00:17:19,640
BUT HOLISTIC CHARACTERIZATION

521
00:17:19,640 --> 00:17:19,920
APPROACH.

522
00:17:19,920 --> 00:17:22,000
SO WE DESIGNED A SCREENING

523
00:17:22,000 --> 00:17:27,560
PLATFORM THAT ALLOWED US TO DO

524
00:17:27,560 --> 00:17:28,320
MULTICHARACTER -- BRIGHTNESS,

525
00:17:28,320 --> 00:17:29,880
PHOTO STABILITY AND RESPONSE TO

526
00:17:29,880 --> 00:17:34,800
DEEP FLUOROIZATION FOR EACH

527
00:17:34,800 --> 00:17:35,680
TESTED.

528
00:17:35,680 --> 00:17:39,600
WE SCREENED OUR VARIANTS BASED

529
00:17:39,600 --> 00:17:41,920
OFF OF THE ACES SCAFFOLD, A

530
00:17:41,920 --> 00:17:42,880
VOLTAGE SENSITIVE DOMAIN

531
00:17:42,880 --> 00:17:45,840
ATTACHED TO A CIRCLELY PER MUTED

532
00:17:45,840 --> 00:17:46,800
EXTRACELLULAR GFP.

533
00:17:46,800 --> 00:17:50,400
WE TARGETED STRUCTURALLY AND

534
00:17:50,400 --> 00:17:52,160
EVOLUTIONARY RESIDUES INCLUDING

535
00:17:52,160 --> 00:17:54,360
AMINO ACIDS TO INTERACT WITH THE

536
00:17:54,360 --> 00:17:55,240
FLUORESCENT PROTEIN OR ARE

537
00:17:55,240 --> 00:17:56,560
CRITICAL TO THE FUNCTION OF THE

538
00:17:56,560 --> 00:17:59,840
VOLTAGE SENSING DOMAIN.

539
00:17:59,840 --> 00:18:01,360
AFTER THOUSANDS OF VARIANTS

540
00:18:01,360 --> 00:18:02,880
TESTED, WE'RE EXCITED TO SAY WE

541
00:18:02,880 --> 00:18:06,480
IDENTIFIED A NEW GEVI NAMED

542
00:18:06,480 --> 00:18:09,120
JELLYFISH DERIVED VOLTAGE

543
00:18:09,120 --> 00:18:10,760
INDICATORS FOR TWO PHOTON

544
00:18:10,760 --> 00:18:11,200
IMAGING.

545
00:18:11,200 --> 00:18:15,360
OR JEDI-2P FOR SHORT, WHICH CAN

546
00:18:15,360 --> 00:18:17,760
DETECT INDIVIDUAL ACTION

547
00:18:17,760 --> 00:18:21,280
POTENTIALS FOR OVER 40 MINUTES

548
00:18:21,280 --> 00:18:24,360
AND 270 MICRO METERS OF THE

549
00:18:24,360 --> 00:18:25,960
SURFACE OF THE MOUSE BRAIN USING

550
00:18:25,960 --> 00:18:28,040
TWO PHOTON MICROSCOPY.

551
00:18:28,040 --> 00:18:30,440
AND IS SHOWN RIGHT HERE IN THE

552
00:18:30,440 --> 00:18:32,440
SLIDE.

553
00:18:32,440 --> 00:18:33,440
JEDI-2P HAS BEEN SUCCESSFULLY

554
00:18:33,440 --> 00:18:35,920
TESTED IN ISOLATED MOUSE RETINA,

555
00:18:35,920 --> 00:18:37,240
DROSOPHILA AND FISH.

556
00:18:37,240 --> 00:18:43,960
THUS SHOWING GREAT -- JEDI-2P OF

557
00:18:43,960 --> 00:18:46,320
COURSE IS NOT THE LAST JEDI, AND

558
00:18:46,320 --> 00:18:47,400
WE'RE CONTINUING TO MAKE

559
00:18:47,400 --> 00:18:48,160
ADVANCEMENTS.

560
00:18:48,160 --> 00:18:49,800
SO IF YOU'RE INTERESTED IN

561
00:18:49,800 --> 00:18:52,960
TRYING OUT JEDI-2P OR ANY OF OUR

562
00:18:52,960 --> 00:19:00,200
NEWEST SENSORS, PLEASE CONTACT

563
00:19:00,200 --> 00:19:05,160
US THROUGH EMAIL OR QR CODE.

564
00:19:05,160 --> 00:19:08,000
OVER LONGER TIME SPANS AND

565
00:19:08,000 --> 00:19:09,200
ADVANCE OUR UNDERSTANDING OF

566
00:19:09,200 --> 00:19:10,840
NEURAL DATA PROCESSING IN HEALTH

567
00:19:10,840 --> 00:19:11,720
AND DISEASE.

568
00:19:11,720 --> 00:19:13,280
THANK YOU FOR YOUR TIME, AND IF

569
00:19:13,280 --> 00:19:14,680
YOU HAVE ANY ADDITIONAL

570
00:19:14,680 --> 00:19:21,440
QUESTIONS, PLEASE CONTACT TO

571
00:19:21,440 --> 00:19:21,680
DISCUSS.

572
00:19:21,680 --> 00:19:27,120
>> HELLO, EVERYONE.

573
00:19:27,120 --> 00:19:28,320
I'M EXCITED TO TALK TO YOU ABOUT

574
00:19:28,320 --> 00:19:33,800
MY RESEARCH, WHICH IS RESTORING

575
00:19:33,800 --> 00:19:35,080
SENSATION AFTER LOWER LIMB

576
00:19:35,080 --> 00:19:36,520
AMPUTATION USING SPINAL CORD

577
00:19:36,520 --> 00:19:37,120
STIMULATION.

578
00:19:37,120 --> 00:19:38,840
THE PEOPLE WITH LOWER LIMB

579
00:19:38,840 --> 00:19:40,800
AMPUTATION HAVE PROCESSES WHICH

580
00:19:40,800 --> 00:19:41,760
LACK SENSORY FEEDBACK.

581
00:19:41,760 --> 00:19:44,480
NOW THE SENSORY FEEDBACK IS NOT

582
00:19:44,480 --> 00:19:45,680
JUST IMPORTANT FOR SOMEONE TO

583
00:19:45,680 --> 00:19:47,920
FEEL THEIR LEGS, BUT AT THE SAME

584
00:19:47,920 --> 00:19:50,960
TIME, IT PLAYS A CRUCIAL ROLE IN

585
00:19:50,960 --> 00:19:52,520
DIFFERENT LOWER LIMB FUNCTIONS

586
00:19:52,520 --> 00:19:55,360
LIKE MAINTAINING BALANCE OR

587
00:19:55,360 --> 00:19:55,760
GAIT.

588
00:19:55,760 --> 00:19:58,320
SO WE WANT TO RESTORE THIS

589
00:19:58,320 --> 00:19:59,480
MISSING SENSATION USING A

590
00:19:59,480 --> 00:20:01,440
CLINICALLY APPROVED TECHNOLOGY

591
00:20:01,440 --> 00:20:04,400
CALLED SPINAL CORD STIMULATION.

592
00:20:04,400 --> 00:20:06,400
CURRENTLY THIS TECHNOLOGY IS

593
00:20:06,400 --> 00:20:07,600
USED TO TREAT CHRONIC PAIN AND

594
00:20:07,600 --> 00:20:09,040
WE WANT TO USE THE SAME

595
00:20:09,040 --> 00:20:10,440
TECHNOLOGY TO SEE IF WE CAN

596
00:20:10,440 --> 00:20:13,400
RESTORE MISSING 16   SENSATIONSN

597
00:20:13,400 --> 00:20:14,080
THESE AMPUTEES.

598
00:20:14,080 --> 00:20:16,160
SO WE HAVE IMPLANTED THREE

599
00:20:16,160 --> 00:20:18,720
SUBJECTS SO FAR.

600
00:20:18,720 --> 00:20:20,080
WE PLACED THESE FLEXIBLE LEADS

601
00:20:20,080 --> 00:20:21,760
AS YOU CAN SEE IN THE FIGURE IN

602
00:20:21,760 --> 00:20:24,440
THE LUMBAR REGION OF THE SPINAL

603
00:20:24,440 --> 00:20:27,600
CORD, AND WE HAVE SEEN THAT

604
00:20:27,600 --> 00:20:29,160
SUCCESSFULLY IN AMPUTEE, WE

605
00:20:29,160 --> 00:20:30,440
COULD EVOKE SENSATIONS IN THE

606
00:20:30,440 --> 00:20:35,920
MISSING LIMB, AND THESE EVOKED

607
00:20:35,920 --> 00:20:37,120
SENSATIONS ALSO IMPROVE THE

608
00:20:37,120 --> 00:20:38,400
LOWER LIMB FUNCTIONS.

609
00:20:38,400 --> 00:20:39,840
I'M EXCITED TO SEE YOU ALL IN MY

610
00:20:39,840 --> 00:20:40,080
POSTER.

611
00:20:40,080 --> 00:20:41,480
THANK YOU FOR LISTENING

612
00:20:41,480 --> 00:20:42,440
FLEURCHLT     

613
00:20:42,440 --> 00:20:43,600
>> HELLO, EVERYONE.

614
00:20:43,600 --> 00:20:47,120
MY NAME IS NATALIE AND I WORK AS

615
00:20:47,120 --> 00:20:49,280
A POSTDOC IN THE DEPARTMENT OF

616
00:20:49,280 --> 00:20:51,480
BIOMEDICAL ENGINEERING AT BOSTON

617
00:20:51,480 --> 00:20:57,920
UNIVERSITY.

618
00:20:57,920 --> 00:20:59,960
IT'S A WIDELY USED TECHNIQUE IN

619
00:20:59,960 --> 00:21:01,400
HUMANS TO STUDY BRAIN FUNCTION

620
00:21:01,400 --> 00:21:02,520
IN HEALTH AND DISEASE.

621
00:21:02,520 --> 00:21:04,760
HOWEVER, THIS TECHNIQUE DOES NOT

622
00:21:04,760 --> 00:21:06,640
DIRECTLY MEASURE NEURONAL

623
00:21:06,640 --> 00:21:09,200
ACTIVITY, BUT RATHER REFLECTS A

624
00:21:09,200 --> 00:21:10,680
BALANCE BETWEEN OXYGEN DELIVERY

625
00:21:10,680 --> 00:21:14,440
AND OXYGEN CONSUMPTION.

626
00:21:14,440 --> 00:21:19,240
MY GOAL WAS TO ESTIMATE OXYGEN

627
00:21:19,240 --> 00:21:21,520
CONSUMPTION OR CEREBRAL

628
00:21:21,520 --> 00:21:23,160
METABOLIC RATE OF OXYGEN IN THE

629
00:21:23,160 --> 00:21:28,720
BRAIN OF MICE WITH PHOTO

630
00:21:28,720 --> 00:21:29,640
MICROSCOPY.

631
00:21:29,640 --> 00:21:31,040
USING OXYGEN CONSUMPTION

632
00:21:31,040 --> 00:21:32,360
TOGETHER WITH BLOOD FLOW AND

633
00:21:32,360 --> 00:21:34,640
NEURONAL ACTIVITY,

634
00:21:34,640 --> 00:21:38,920
MICROSCOPICALLY CAN BE USED TO

635
00:21:38,920 --> 00:21:40,360
MODEL POLYMERIZED SIGNALS IN

636
00:21:40,360 --> 00:21:42,320
HUMANS.

637
00:21:42,320 --> 00:21:49,640
SO I USED OXYGEN ON AN OXYGEN

638
00:21:49,640 --> 00:21:54,480
SENSOR OXYPHOR 2P -- THAT HAVE

639
00:21:54,480 --> 00:21:59,800
BEEN USE FORD A LONG TIME,

640
00:21:59,800 --> 00:22:01,120
OXYPHOR 2P ALLOWS ME TO MEASURE

641
00:22:01,120 --> 00:22:02,880
TO THE HIGHEST SPATIAL

642
00:22:02,880 --> 00:22:03,400
RESOLUTION.

643
00:22:03,400 --> 00:22:05,560
I INJECTED THE DYE INTO THE I

644
00:22:05,560 --> 00:22:09,760
HAVE SIPT OF AN         

645
00:22:09,760 --> 00:22:12,360
VICINITY IN THE MOUSE CORTEX.

646
00:22:12,360 --> 00:22:14,480
THEN I FOLLOWED THE ARTERY DOWN

647
00:22:14,480 --> 00:22:16,440
TO LAYER FOUR AND I CREATED --

648
00:22:16,440 --> 00:22:18,720
AROUND THE ARTERY TO MEASURE HOW

649
00:22:18,720 --> 00:22:24,640
OXYGEN DIFFUSES INTO THE TISSUE.

650
00:22:24,640 --> 00:22:27,920
AT THIS POINT I MEASURE THE

651
00:22:27,920 --> 00:22:28,880
PHOTON DECAY.

652
00:22:28,880 --> 00:22:34,720
BECAUSE I EXCITE THE FOS   PHOSS

653
00:22:34,720 --> 00:22:37,720
IN DYE FIRST AND DEPENDENT ON

654
00:22:37,720 --> 00:22:42,560
HOW MUCH OXYGEN IS PRESENT --

655
00:22:42,560 --> 00:22:50,360
THEN I CONVERTED TO PO2 AND

656
00:22:50,360 --> 00:22:52,000
CREATE A PO2 MAP ON TOP OF THE

657
00:22:52,000 --> 00:22:52,400
VESSEL MAP.

658
00:22:52,400 --> 00:22:54,160
AS YOU CAN SEE HERE IN THE

659
00:22:54,160 --> 00:22:55,480
VESSEL MAP ON THE RIGHT SIDE,

660
00:22:55,480 --> 00:22:57,360
THE OXYGEN IS HIGH INSIDE THE

661
00:22:57,360 --> 00:23:01,920
VESSEL AND THEN IF YOU GO

662
00:23:01,920 --> 00:23:03,120
TOWARDS THE PERIPHERY, THE

663
00:23:03,120 --> 00:23:04,320
OXYGEN DROPS.

664
00:23:04,320 --> 00:23:05,680
THIS DROP OF OXYGEN OR GRADE

665
00:23:05,680 --> 00:23:08,080
YENT OF OXYGEN IS DEPENDENT ON

666
00:23:08,080 --> 00:23:16,320
HOW MUCH OXYGEN IS CONSUMED.

667
00:23:16,320 --> 00:23:20,080
THE DEEPER THE GREAT YENT,     E

668
00:23:20,080 --> 00:23:21,280
MORE OXYGEN IS CONSUMED.

669
00:23:21,280 --> 00:23:22,080
AFTER I WENT THROUGH THE LAYERS

670
00:23:22,080 --> 00:23:27,080
IN THE CORTEX, WE COULD SEE THAT

671
00:23:27,080 --> 00:23:30,600
LAYER ONE IN BLUE HAS THE

672
00:23:30,600 --> 00:23:31,840
STEEPEST GRADIENT, INDICATING

673
00:23:31,840 --> 00:23:34,320
THE HIGHEST OXYGEN CONSUMPTION.

674
00:23:34,320 --> 00:23:37,800
THIS IS IN CONTRAST TO THE

675
00:23:37,800 --> 00:23:39,560
COMMON BELIEF IN THE FIELD THAT

676
00:23:39,560 --> 00:23:41,120
OXYGEN CONSUMPTION IS HIGHEST IN

677
00:23:41,120 --> 00:23:42,400
LAYER FOUR, BECAUSE IN LAYER

678
00:23:42,400 --> 00:23:44,800
FOUR, WE HAVE THE HIGHEST

679
00:23:44,800 --> 00:23:46,760
NEURONAL DENSITY AND ALSO

680
00:23:46,760 --> 00:23:52,560
CAPILLARY DENSITY.

681
00:23:52,560 --> 00:23:56,400
AND CYTOCHROME -- FOR OXIDATIVE

682
00:23:56,400 --> 00:24:00,360
PHOSPHORYLATION LOCATED IN THE

683
00:24:00,360 --> 00:24:02,200
MITOCHONDRIAL BRAIN, IT'S MORE

684
00:24:02,200 --> 00:24:05,040
PREVALENT THEREFORE.

685
00:24:05,040 --> 00:24:06,040
HOWEVER, THIS TECHNIQUE COULD

686
00:24:06,040 --> 00:24:08,080
SHOW THIS IS NOT THE CASE IN THE

687
00:24:08,080 --> 00:24:08,760
MOUSE CORTEX.

688
00:24:08,760 --> 00:24:10,880
THEN WE THOUGHT IT MIGHT BE

689
00:24:10,880 --> 00:24:13,400
UNDER STIMULATING CONDITIONS ON

690
00:24:13,400 --> 00:24:15,640
THE AXIAL BRAIN STATES WHEN WE

691
00:24:15,640 --> 00:24:20,480
NEED A HIGHER CONSUMPTION IN

692
00:24:20,480 --> 00:24:20,760
LAYER FOUR.

693
00:24:20,760 --> 00:24:23,240
HOWEVER, PRELIMINARY DATA SHOWS

694
00:24:23,240 --> 00:24:25,800
AS WELL THAT THE OXYGEN

695
00:24:25,800 --> 00:24:27,240
CONSUMPTION IS HIGHEST IN LAYER

696
00:24:27,240 --> 00:24:33,360
ONE AND THEN DECREASES WITH

697
00:24:33,360 --> 00:24:35,560
LAYER TWO THROUGH LAYER FOUR.

698
00:24:35,560 --> 00:24:39,400
THE TECHNIQUE I PRESENT HERE

699
00:24:39,400 --> 00:24:40,680
SHOWS A POWERFUL TOOL THAT CAN

700
00:24:40,680 --> 00:24:43,000
BE USED IN HEALTH AND DISEASE

701
00:24:43,000 --> 00:24:48,920
MODELS AND IT CAN BE USED TO

702
00:24:48,920 --> 00:24:50,320
MODEL FMRI SIGNALS.

703
00:24:50,320 --> 00:24:51,440
THANK YOU VERY MUCH FOR YOUR

704
00:24:51,440 --> 00:24:52,320
ATTENTION.

705
00:24:52,320 --> 00:24:53,600
>> HELLO, EVERYONE.

706
00:24:53,600 --> 00:24:55,160
MY NAME IS CARL AND I'M EXCITED

707
00:24:55,160 --> 00:24:56,880
TO TALK ABOUT MY RESEARCH HERE

708
00:24:56,880 --> 00:24:59,240
AT UT SOUTHWESTERN MEDICAL

709
00:24:59,240 --> 00:25:00,280
CENTER.

710
00:25:00,280 --> 00:25:01,600
THE OVERALL GOAL OF MY PROJECT

711
00:25:01,600 --> 00:25:03,880
IS TO UNDERSTAND THE CELL TYPES

712
00:25:03,880 --> 00:25:06,080
THAT ARE ENGAGED IN THE BRAIN

713
00:25:06,080 --> 00:25:07,600
CIRCUITS FOR VOCAL LEARNING AND

714
00:25:07,600 --> 00:25:09,960
WHAT VOCAL LEARNING IS IS THE

715
00:25:09,960 --> 00:25:13,400
ABILITY TO MODIFY VOCALIZATIONS

716
00:25:13,400 --> 00:25:15,600
OR ACOUSTIC SOUNDS AND VOCAL

717
00:25:15,600 --> 00:25:16,800
LEARNING IS A CRITICAL COMPONENT

718
00:25:16,800 --> 00:25:18,440
OF HUMAN SPEECH, BUT IT'S

719
00:25:18,440 --> 00:25:21,440
DIFFICULT TO STUDY IN CLASSICAL

720
00:25:21,440 --> 00:25:23,680
MODEL ORGANISMS SUCH AS MICE AND

721
00:25:23,680 --> 00:25:25,880
NON-HUMAN PRIMATES BECAUSE THEY

722
00:25:25,880 --> 00:25:27,160
DO NOT EXHIBIT VOCAL LEARNING

723
00:25:27,160 --> 00:25:27,520
BEHAVIOR.

724
00:25:27,520 --> 00:25:30,240
SO IN OUR LAB, WE USED SONG

725
00:25:30,240 --> 00:25:31,240
BIRDS WHICH LEARN THEIR SONG

726
00:25:31,240 --> 00:25:32,960
VERY SIMILAR TO THE WAY HUMANS

727
00:25:32,960 --> 00:25:34,960
LEARN LANGUAGE.

728
00:25:34,960 --> 00:25:37,280
WE SPECIFICALLY USED ZEBRA

729
00:25:37,280 --> 00:25:39,000
FINCHES BECAUSE THEIR VOCAL

730
00:25:39,000 --> 00:25:40,200
LEARNING STAGES ARE MOST SIMILAR

731
00:25:40,200 --> 00:25:41,400
TO HUMANS.

732
00:25:41,400 --> 00:25:46,000
THEY BOTH NEED TO HEAR SPECIFIC

733
00:25:46,000 --> 00:25:47,200
VOCALIZATIONS EARLY IN THEIR

734
00:25:47,200 --> 00:25:48,880
DEVELOPMENT WHEN THEIR BRAIRNS

735
00:25:48,880 --> 00:25:53,760
AND          BRAINS ARE VERY

736
00:25:53,760 --> 00:25:54,720
PLASTIC.

737
00:25:54,720 --> 00:25:56,840
THE SENSORY LEARNING PERIOD OR

738
00:25:56,840 --> 00:25:57,600
SENSORY LEARNING STAGE.

739
00:25:57,600 --> 00:25:59,320
WE KNOW THAT THERE ARE

740
00:25:59,320 --> 00:26:01,640
SIMILARITIES IN BEHAVIOR AND

741
00:26:01,640 --> 00:26:03,480
DEVELOPMENT IN THEIR VOCAL

742
00:26:03,480 --> 00:26:07,880
LEARNING BEHAVIOR WITH YOU     O

743
00:26:07,880 --> 00:26:09,600
IDENTIFIED -- FOR CONTROL OF

744
00:26:09,600 --> 00:26:10,400
VOCALIZATION.

745
00:26:10,400 --> 00:26:11,680
ALTHOUGH WE KNOW IN GENERAL THE

746
00:26:11,680 --> 00:26:13,800
BRAIN REGION INVOLVED IN SPEECH

747
00:26:13,800 --> 00:26:15,000
AND SOUND CONTROL, WE DON'T KNOW

748
00:26:15,000 --> 00:26:16,840
WHAT IS OCCURRING AT THE

749
00:26:16,840 --> 00:26:17,840
CELLULAR RESOLUTION AND HOW IT'S

750
00:26:17,840 --> 00:26:19,680
CHANGING THROUGHOUT DEVELOPMENT

751
00:26:19,680 --> 00:26:21,680
DURING THESE SENSITIVE PERIODS

752
00:26:21,680 --> 00:26:22,960
WHEN THEY ARE LEARNING SONG OR

753
00:26:22,960 --> 00:26:23,840
SPEECH.

754
00:26:23,840 --> 00:26:25,040
SO HOW DO WE ANSWER THIS

755
00:26:25,040 --> 00:26:26,480
QUESTION OF WHAT ARE THE CELL

756
00:26:26,480 --> 00:26:28,520
TYPES ENGAGED DURING DIFFERENT

757
00:26:28,520 --> 00:26:29,400
VOCAL LEARNING STAGES?

758
00:26:29,400 --> 00:26:31,920
WELL, FOR THIS, WE DISSECTED A

759
00:26:31,920 --> 00:26:33,920
SPECIFIC BRAIN REGION SONG BIRDS

760
00:26:33,920 --> 00:26:35,360
NECESSARY BOTH FOR SONG LEARNING

761
00:26:35,360 --> 00:26:36,640
AND PRODUCTION AND THAT IS

762
00:26:36,640 --> 00:26:38,600
ANALOGOUS TO THE PREMOTOR CORTEX

763
00:26:38,600 --> 00:26:40,160
FOR CONTROLLING VOCALIZATION IN

764
00:26:40,160 --> 00:26:40,720
HUMANS.

765
00:26:40,720 --> 00:26:47,240
WE CONDUCTED SINGLE RNA -- AT

766
00:26:47,240 --> 00:26:49,440
DIFFERENT TIME POINTS AT 24 AND

767
00:26:49,440 --> 00:26:50,440
45 DAYS POST HATCH AND WE

768
00:26:50,440 --> 00:26:52,720
COMPARED TO ADULTS.

769
00:26:52,720 --> 00:26:55,120
AND WE SPECIFICALLY FOCUSED ON

770
00:26:55,120 --> 00:26:57,080
USING THIS DATA GENE EXPRESSION

771
00:26:57,080 --> 00:26:58,840
DATA WHERE WE DID A PRINCIPAL

772
00:26:58,840 --> 00:27:02,480
COMPONENT ANALYSIS AND REDUCTION

773
00:27:02,480 --> 00:27:03,760
TO IDENTIFY MEAN CELL CLUSTERS

774
00:27:03,760 --> 00:27:09,560
THAT WE CAN THEN LABEL USING THE

775
00:27:09,560 --> 00:27:10,200
GEN EXPRESSION HERE.

776
00:27:10,200 --> 00:27:14,160
WE CAN IDENTIFY THE MAJOR CELL

777
00:27:14,160 --> 00:27:21,600
TYPES SUCH AS THE GABA AND OTHER

778
00:27:21,600 --> 00:27:23,240
GLIAL -- THAT PROJECT EITHER TO

779
00:27:23,240 --> 00:27:25,760
THE BASAL GANGLIA, AUDITORY

780
00:27:25,760 --> 00:27:27,480
REGION OR MOTOR PATHWAY.

781
00:27:27,480 --> 00:27:29,400
ONCE WE CAN IDENTIFY THESE VEL

782
00:27:29,400 --> 00:27:31,680
TYPES,       CELL

783
00:27:31,680 --> 00:27:33,320
TYPES, WE CAN FOCUS ON HOW IT'S

784
00:27:33,320 --> 00:27:34,000
CHANGING THROUGH THIS

785
00:27:34,000 --> 00:27:35,000
DEVELOPMENT AND COMPARE TO

786
00:27:35,000 --> 00:27:36,400
ADULTS WHICH IS SHOWN HERE, A

787
00:27:36,400 --> 00:27:37,800
PERCENTAGE OF A SPECIFIC CELL

788
00:27:37,800 --> 00:27:41,200
TYPE TO ALL OF THE PROJECTION

789
00:27:41,200 --> 00:27:42,840
TYPES AND REMARKABLY WHAT WE

790
00:27:42,840 --> 00:27:44,600
FOUND THAT HAS BEEN REPORTED

791
00:27:44,600 --> 00:27:45,920
BEFORE BUT NOT WITH THAT TYPE OF

792
00:27:45,920 --> 00:27:48,120
DATA IS THAT THE MOTOR

793
00:27:48,120 --> 00:27:49,320
PROJECTING NEURONS IN ADULTS ARE

794
00:27:49,320 --> 00:27:51,400
THE ONES THAT ARE THE LARGEST

795
00:27:51,400 --> 00:27:52,600
PERCENTAGE IN ADULTS SHOWN HERE

796
00:27:52,600 --> 00:27:54,000
IN THE BLACK BAR, BUT ARE NOT

797
00:27:54,000 --> 00:27:56,440
REALLY AS HIGH AS JUVENILES.

798
00:27:56,440 --> 00:27:58,160
BUT IF YOU CONTRAST THIS WITH

799
00:27:58,160 --> 00:27:59,680
THE YOUNG BIRDS, YOU CAN SEE THE

800
00:27:59,680 --> 00:28:00,680
AUDITORY PROJECTION NEURONS MAKE

801
00:28:00,680 --> 00:28:05,160
UP THE MAJORITY OF THE

802
00:28:05,160 --> 00:28:06,920
POPULATION WHILE IT REALLY

803
00:28:06,920 --> 00:28:08,120
DECREASES DRASTICALLY IN ADULT

804
00:28:08,120 --> 00:28:08,560
POPULATION.

805
00:28:08,560 --> 00:28:11,840
SO THIS DEMONSTRATED THAT THE

806
00:28:11,840 --> 00:28:14,560
DRAMATIC CHANGE IN CELL TYPE

807
00:28:14,560 --> 00:28:15,680
COMPOSITION COULD MAKE A

808
00:28:15,680 --> 00:28:18,760
POTENTIAL MECHANISM FOR HOW THIS

809
00:28:18,760 --> 00:28:22,360
SOUND KROAL    CONTROL REGION FS

810
00:28:22,360 --> 00:28:23,880
WHEN THE BRAIN IS STILL MATURING

811
00:28:23,880 --> 00:28:25,200
AND CAN CHANGE THROUGHOUT

812
00:28:25,200 --> 00:28:27,240
DEVELOPMENT TO ACCOMMODATE

813
00:28:27,240 --> 00:28:28,280
DIFFERENT METHODS OF LEARNING

814
00:28:28,280 --> 00:28:30,440
THAT CAN APPLY NOT ONLY TO SONG

815
00:28:30,440 --> 00:28:31,840
BIRD LEARNING BUT ALSO HUMAN

816
00:28:31,840 --> 00:28:34,280
SPEECH LEARNING.

817
00:28:34,280 --> 00:28:35,360
WITH THAT, I WANT TO THANK

818
00:28:35,360 --> 00:28:37,680
EVERYONE FOR LISTENING TO MY

819
00:28:37,680 --> 00:28:38,640
TALK AND I'LL BE HAPPY TO TAKE

820
00:28:38,640 --> 00:28:42,360
ANY QUESTIONS HERE OR IN THE

821
00:28:42,360 --> 00:28:42,720
POSTER SESSION.

822
00:28:42,720 --> 00:28:43,040
THANK YOU.

823
00:28:43,040 --> 00:28:46,520
>> HI, MY NAME IS MICHELLE

824
00:28:46,520 --> 00:28:47,520
FALLA, GEORGETOWN UNIVERSITY,

825
00:28:47,520 --> 00:28:51,560
BEGINNING MY SECOND YEAR IN THE

826
00:28:51,560 --> 00:28:52,960
INTERDISCIPLINARY PROGRAM IN

827
00:28:52,960 --> 00:28:53,320
NEUROSCIENCE.

828
00:28:53,320 --> 00:28:58,440
I WORK IN DR. REBECCA EVANS' LAB

829
00:28:58,440 --> 00:29:00,080
INVESTIGATING HOW THE PPN INACTS

830
00:29:00,080 --> 00:29:02,480
WITH THE BASAL GANGLIA TO

831
00:29:02,480 --> 00:29:04,240
MODULATE MOVEMENT.

832
00:29:04,240 --> 00:29:06,440
PREVIOUS STUDIES HAVE

833
00:29:06,440 --> 00:29:07,640
CONTRADICTORY OUTCOMES WHERE

834
00:29:07,640 --> 00:29:08,600
SOMETIMES LOCOMOTION IS

835
00:29:08,600 --> 00:29:09,840
INCREASED AND OTHER TIMES

836
00:29:09,840 --> 00:29:11,040
LOCOMOTION IS DECREASED.

837
00:29:11,040 --> 00:29:14,280
IN FACT, DEEP BRAIN STIMULATION

838
00:29:14,280 --> 00:29:17,040
OF THE PPN IN A PARKINSONIAN RAT

839
00:29:17,040 --> 00:29:19,640
MODEL RESULTED IN WORSENED GAIT

840
00:29:19,640 --> 00:29:21,200
WHEREAS CAUDAL STIMULATION LED

841
00:29:21,200 --> 00:29:23,240
TO IMPROVED GAIT.

842
00:29:23,240 --> 00:29:24,920
FUNCTIONALLY DISTINCT

843
00:29:24,920 --> 00:29:26,880
SUBPOPULATIONS WITHIN THE PPN

844
00:29:26,880 --> 00:29:28,400
CAN HELP EXPLAIN VARIABLE

845
00:29:28,400 --> 00:29:29,200
OUTCOMES IN THE PREVIOUS

846
00:29:29,200 --> 00:29:30,240
LITERATURE, BUT ALSO VARIABLE

847
00:29:30,240 --> 00:29:32,200
OUTCOMES OF PPN-TARGETED DEEP

848
00:29:32,200 --> 00:29:34,280
BRAIN STIMULATION IN PARKINSON'S

849
00:29:34,280 --> 00:29:35,440
DISEASE PATIENTS.

850
00:29:35,440 --> 00:29:37,480
MY WORK FOCUSES ON THE

851
00:29:37,480 --> 00:29:39,800
CHOLINERGIC PPN NEURONS WHOSE

852
00:29:39,800 --> 00:29:40,840
DEGENERATION IN PARKINSON'S

853
00:29:40,840 --> 00:29:42,640
DISEASE CORRELATES WITH GAIT

854
00:29:42,640 --> 00:29:44,040
IMPAIRMENT IN BOTH PATIENTS AND

855
00:29:44,040 --> 00:29:47,200
RODENT MODELS.

856
00:29:47,200 --> 00:29:50,080
I'M USING A MOUSE MODEL TO

857
00:29:50,080 --> 00:29:50,960
CHARACTERIZE THE PROPERTIES OF

858
00:29:50,960 --> 00:29:52,680
THE PPN NEURONS WHICH WILL

859
00:29:52,680 --> 00:29:54,000
FLORES RED UNDER GREEN LIGHT AS

860
00:29:54,000 --> 00:29:55,960
YOU CAN SEE IN THIS FIRST IMAGE.

861
00:29:55,960 --> 00:29:57,520
IT IS COMMON FOR YOUNG MICE TO

862
00:29:57,520 --> 00:29:59,800
BE USED IN ELECTROPHYSIOLOGY

863
00:29:59,800 --> 00:30:01,560
EXPERIMENTS STUDYING THE PPN.

864
00:30:01,560 --> 00:30:03,080
BUT THIS IS NOT SUITABLE FOR

865
00:30:03,080 --> 00:30:04,920
RESEARCH RELATED TO DISEASES

866
00:30:04,920 --> 00:30:06,240
WHICH ARE MORE COMMON WITH AGE

867
00:30:06,240 --> 00:30:08,120
LIKE PARKINSON'S DISEASE.

868
00:30:08,120 --> 00:30:10,840
SO I USED WHOLE CELL PATCH CLAMP

869
00:30:10,840 --> 00:30:12,440
TO RECORD NEURONAL ACTIVITY FROM

870
00:30:12,440 --> 00:30:15,000
THE CHOLINERGIC PPN NEURONS AND

871
00:30:15,000 --> 00:30:16,640
ANALYZED THE DATA BY SEX AND

872
00:30:16,640 --> 00:30:17,480
AGE.

873
00:30:17,480 --> 00:30:18,480
I FOUND SIGNIFICANT DIFFERENCES

874
00:30:18,480 --> 00:30:21,040
IN THE INTRINSIC

875
00:30:21,040 --> 00:30:22,360
ELECTROPHYSIOLOGICAL PROPERTIES

876
00:30:22,360 --> 00:30:24,520
AND THE ROSTRAL CAUDAL

877
00:30:24,520 --> 00:30:26,600
DISTRIBUTION OF CHOLINERGIC

878
00:30:26,600 --> 00:30:27,360
ELECTROPHYSIOLOGICAL SUBTYPES IN

879
00:30:27,360 --> 00:30:28,560
ADULT MICE COMPARED TO MICE

880
00:30:28,560 --> 00:30:30,440
UNDER TWO MONTHS OF AGE.

881
00:30:30,440 --> 00:30:32,480
WE ARE WORKING TO DETERMINE THE

882
00:30:32,480 --> 00:30:34,600
FUNCTIONAL SIGNIFICANCE OF THESE

883
00:30:34,600 --> 00:30:36,000
ROSTRAL CAUDAL DIFFERENCES.

884
00:30:36,000 --> 00:30:38,280
SO WE WANTED TO DETERMINE IF THE

885
00:30:38,280 --> 00:30:41,240
CAUDAL AND ROSTRAL PPN RECEIVE

886
00:30:41,240 --> 00:30:42,360
DIFFERENTIAL INNERVATION FROM

887
00:30:42,360 --> 00:30:48,360
THE INHIBITORY BASAL GANGLION

888
00:30:48,360 --> 00:30:54,600
NUCLEI.

889
00:30:54,600 --> 00:30:57,520
WE CAN OPT GENETICALLY STIMULATE

890
00:30:57,520 --> 00:30:59,240
THE AXONS PRESENTING TO THE PPN

891
00:30:59,240 --> 00:31:00,480
WHILE RECORDING THE INHIBITORY

892
00:31:00,480 --> 00:31:01,920
INPUT TO THE CHOLINERGIC

893
00:31:01,920 --> 00:31:02,360
NEURONS.

894
00:31:02,360 --> 00:31:04,320
IN THIS IMAGE, WE CAN SEE HOW

895
00:31:04,320 --> 00:31:05,840
THESE GREEN AXONAL PROJECTIONS

896
00:31:05,840 --> 00:31:08,160
FROM THE GPE EXTEND OVER AND

897
00:31:08,160 --> 00:31:15,480
THROUGH THE CAUDAL PPN.

898
00:31:15,480 --> 00:31:17,560
THE DISTRIBUTION OF AXONAL

899
00:31:17,560 --> 00:31:18,880
PROJECTIONS IN IMAGING WERE

900
00:31:18,880 --> 00:31:21,840
SUPPORTED BY THE RECORDED

901
00:31:21,840 --> 00:31:22,720
INPUTS.

902
00:31:22,720 --> 00:31:25,280
THE SNR INNERVATES ABOUT 80% OF

903
00:31:25,280 --> 00:31:27,280
THE NEURONS WITH RELATIVELY

904
00:31:27,280 --> 00:31:29,360
EQUAL INNERVATION OF THE ROSS

905
00:31:29,360 --> 00:31:31,440
STRAL AND CAUDAL PPN.

906
00:31:31,440 --> 00:31:33,720
THE PPN RECEIVES MUCH LESS

907
00:31:33,720 --> 00:31:35,960
INNERVATION FROM THE GPE WITH

908
00:31:35,960 --> 00:31:37,560
ABOUT 40% OF THE PATCH NEURONS

909
00:31:37,560 --> 00:31:38,560
RECEIVING INHIBITORY INPUT.

910
00:31:38,560 --> 00:31:40,120
MOST OF THE NEURONS THAT WERE

911
00:31:40,120 --> 00:31:41,520
CONNECTED TO THE GPE WERE

912
00:31:41,520 --> 00:31:43,480
LOCATED IN THE CAUDAL PPN.

913
00:31:43,480 --> 00:31:47,200
SUPPORTING WHAT WE WITH SEEN INN

914
00:31:47,200 --> 00:31:50,840
THE IMAGING.

915
00:31:50,840 --> 00:31:53,240
WE ARE IN THE PROCESS OF USING

916
00:31:53,240 --> 00:31:54,240
TWO PHOTON IMAGING TO CLASSIFY

917
00:31:54,240 --> 00:31:55,560
THE REGIONAL CONNECTIVITY

918
00:31:55,560 --> 00:31:57,640
BETWEEN THESE NUCLEI IN THE PPN

919
00:31:57,640 --> 00:32:00,080
ACROSS THE ROSTRAL CAUDAL ACCESS

920
00:32:00,080 --> 00:32:02,040
AS WELL AS THE MEDIAL LATERAL

921
00:32:02,040 --> 00:32:02,560
AXIS.

922
00:32:02,560 --> 00:32:03,720
THE LAST THING I'LL SHARE IS

923
00:32:03,720 --> 00:32:05,400
THAT WE STAINED FOR THE

924
00:32:05,400 --> 00:32:09,360
EXTRACELLULAR MATRIX PROTEIN

925
00:32:09,360 --> 00:32:10,560
NPNT BECAUSE IT IS ONLY REALLY

926
00:32:10,560 --> 00:32:13,720
FOUND IN THE CORTEX AND OUR

927
00:32:13,720 --> 00:32:15,240
REGION OF INTEREST, THE PPN.

928
00:32:15,240 --> 00:32:18,400
WE WERE ABLE TO IDENTIFY AN

929
00:32:18,400 --> 00:32:19,040
NPNT-NEGATIVE SUBGROUP WITHIN

930
00:32:19,040 --> 00:32:21,240
THE CAUDAL PPN, SO WE PLAN TO

931
00:32:21,240 --> 00:32:23,120
INVESTIGATE THE INTRINSIC AND

932
00:32:23,120 --> 00:32:26,280
SYNAPTIC PROPERTIES WHICH MAY

933
00:32:26,280 --> 00:32:27,480
DIFFERENTIATE THE CHOLINERGIC

934
00:32:27,480 --> 00:32:30,360
NEURONS AND THE NPNT POSITIVE

935
00:32:30,360 --> 00:32:31,880
CHOLINERGIC NEURONS.

936
00:32:31,880 --> 00:32:32,960
THESE FINDINGS WILL HELP US

937
00:32:32,960 --> 00:32:34,720
BETTER UNDERSTAND HOW THE PPN

938
00:32:34,720 --> 00:32:36,120
RECEIVES REGION-SPECIFIC INPUTS

939
00:32:36,120 --> 00:32:41,080
FROM THE BASAL BEGAN    GANGLIAO

940
00:32:41,080 --> 00:32:42,280
DETERMINE MODULATION ON MOTOR

941
00:32:42,280 --> 00:32:42,520
OUTPUT.

942
00:32:42,520 --> 00:32:43,560
THANK YOU FOR YOUR TIME, AND

943
00:32:43,560 --> 00:32:45,880
PLEASE CHECK OUT POSTER NUMBER

944
00:32:45,880 --> 00:32:48,400
808 FOR MORE INFORMATION.

945
00:32:48,400 --> 00:32:51,440
>> HELLO, EVERYBODY.

946
00:32:51,440 --> 00:32:54,000
I'M A POSTDOCTORAL SCHOLAR AT

947
00:32:54,000 --> 00:32:55,280
THE CEDARS-SINAI MEDICAL CENTER.

948
00:32:55,280 --> 00:32:56,480
TODAY I WOULD LIKE TO INTRODUCE

949
00:32:56,480 --> 00:33:07,160
TO YOU MY RESEARCH IN THANK -- R

950
00:33:07,480 --> 00:33:09,280
TO PERFORM A CERTAIN TASK.

951
00:33:09,280 --> 00:33:11,920
SUCH DISTRACTIONS CAN COME FROM

952
00:33:11,920 --> 00:33:16,400
THE EXTERNAL WORLD SUCH AS A

953
00:33:16,400 --> 00:33:18,360
LOUD RAIN -- OR IT CAN COME FROM

954
00:33:18,360 --> 00:33:21,080
INTERNAL SOURCES SUCH AS OUR OWN

955
00:33:21,080 --> 00:33:24,480
HABITS OR INTRUSIVE THOUGHTS.

956
00:33:24,480 --> 00:33:26,000
WHEN DISTRACTION INTERFERES WITH

957
00:33:26,000 --> 00:33:29,200
OUR GOAL TO A MODERATE EXTENT,

958
00:33:29,200 --> 00:33:32,480
WE EXPERIENCE CONFLICT.

959
00:33:32,480 --> 00:33:34,320
WHEN DESTROYING ENOUGH TO KNOCK

960
00:33:34,320 --> 00:33:35,680
US OFF FROM OUR PATH OF

961
00:33:35,680 --> 00:33:36,520
ACHIEVING A CERTAIN GOAL, WE

962
00:33:36,520 --> 00:33:37,400
MAKE AN ERROR.

963
00:33:37,400 --> 00:33:39,680
FROM OUR PREVIOUS WORK, WE

964
00:33:39,680 --> 00:33:41,440
IDENTIFY NEURONS IN THE HUMAN

965
00:33:41,440 --> 00:33:42,960
MEDIAL FRONTAL CORTEX THAT CAN

966
00:33:42,960 --> 00:33:45,720
DETECT AND SIGNAL THESE

967
00:33:45,720 --> 00:33:46,920
DISTURBANCES ALMOST IMMEDIATELY

968
00:33:46,920 --> 00:33:48,000
AFTER THEY OCCUR, BUT NOW THE

969
00:33:48,000 --> 00:33:51,600
QUESTION IS, CAN THE SAME SET OF

970
00:33:51,600 --> 00:33:54,240
NEURONS DETECT CONFLICT AND

971
00:33:54,240 --> 00:33:55,560
ERROR ACROSS DIFFERENT TASKS OR

972
00:33:55,560 --> 00:33:57,080
DO WE HAVE SPECIALIZED NEURONS

973
00:33:57,080 --> 00:33:57,600
FOR EACH TASK.

974
00:33:57,600 --> 00:33:59,200
THIS IS AN IMPORTANT QUESTION

975
00:33:59,200 --> 00:34:01,240
BECAUSE UNLIKE ARTIFICIAL

976
00:34:01,240 --> 00:34:02,640
INTELLIGENCE AGENTS, HUMANS HAVE

977
00:34:02,640 --> 00:34:04,200
THIS AMAZING ABILITY TO

978
00:34:04,200 --> 00:34:05,480
GENERALIZE.

979
00:34:05,480 --> 00:34:08,240
WE CAN PERFORM MANY DIFFERENT

980
00:34:08,240 --> 00:34:09,440
TASKS AND DEAL WITH ERRORS

981
00:34:09,440 --> 00:34:11,720
DURING THE COURSE OF PER   PERFE

982
00:34:11,720 --> 00:34:13,600
IN ALL OF THESE TASK.

983
00:34:13,600 --> 00:34:15,680
EVEN THOUGH THE SOURCES OF

984
00:34:15,680 --> 00:34:18,640
DISTRACTION CAN DIFFER GREATLY.

985
00:34:18,640 --> 00:34:20,040
MOTIVATED BY SUCH OBSERVATION,

986
00:34:20,040 --> 00:34:21,560
WE TRY TO INVESTIGATE THE NEURAL

987
00:34:21,560 --> 00:34:24,120
MECHANISMS THAT ALLOW THE MEDIAL

988
00:34:24,120 --> 00:34:27,280
FRONTAL CORTEX TO SUPPORT

989
00:34:27,280 --> 00:34:29,000
DOMAIN -- MONITORING.

990
00:34:29,000 --> 00:34:30,640
WE RECORD SINGLE NEURONS FROM

991
00:34:30,640 --> 00:34:32,280
EPILEPSY PATIENTS THAT WERE

992
00:34:32,280 --> 00:34:34,240
MONITORED FOR SEIZURES TO SEE

993
00:34:34,240 --> 00:34:38,760
VAL WAIT WHETHER           

994
00:34:38,760 --> 00:34:41,360
EVALUATE WHETHER THEY'RE A CAN'T

995
00:34:41,360 --> 00:34:45,080
DATE FOR THERAPY.

996
00:34:45,080 --> 00:34:46,240
IN TWO EXPERIMENTAL SESSIONS

997
00:34:46,240 --> 00:34:47,400
WHILE RECORDING FROM THEIR

998
00:34:47,400 --> 00:34:49,120
NEURONS.

999
00:34:49,120 --> 00:34:50,480
WHAT WE FOUND IS THAT A LARGE

1000
00:34:50,480 --> 00:34:53,320
PERCENTAGE OF MEDIAL FORM OF

1001
00:34:53,320 --> 00:34:55,720
CORTICAL NEURONS INDEED ARE

1002
00:34:55,720 --> 00:34:58,120
DOMAIN GENERAL -- CONFLICTS AND

1003
00:34:58,120 --> 00:34:59,560
ERRORS IN BOTH TASKS.

1004
00:34:59,560 --> 00:35:01,080
SOME NEURONS ARE TASK SPECIFIC.

1005
00:35:01,080 --> 00:35:03,480
FOR EXAMPLE, THE SIGNAL ERRORS

1006
00:35:03,480 --> 00:35:06,080
WHEN THE PATIENT -- THE FIRST

1007
00:35:06,080 --> 00:35:08,960
TASK BUT -- SIGNALING ERROR TO

1008
00:35:08,960 --> 00:35:10,440
SWITCH TO A DIFFERENT TASK.

1009
00:35:10,440 --> 00:35:15,480
THIS HIGHLIGHTS THE PERFORMANCE

1010
00:35:15,480 --> 00:35:17,360
MONITORING CAN BE RECONFIGURED

1011
00:35:17,360 --> 00:35:17,800
RAPIDLY.

1012
00:35:17,800 --> 00:35:21,400
IMAGINE THE DOWNSTREAM

1013
00:35:21,400 --> 00:35:24,120
NEURONS -- WHETHER AN ERROR

1014
00:35:24,120 --> 00:35:25,640
OCCURS IN EITHER TASK REGARDLESS

1015
00:35:25,640 --> 00:35:27,520
OF THE REASONS FOR FAILURE, AND

1016
00:35:27,520 --> 00:35:29,320
ONLY LISTEN TO DOMAIN GENERAL

1017
00:35:29,320 --> 00:35:30,480
ERROR NEURONS BUT THIS IS

1018
00:35:30,480 --> 00:35:31,680
IMPOSSIBLE BECAUSE THEY ARE

1019
00:35:31,680 --> 00:35:33,120
INTERMIXED WITH A WHOLE LOT OF

1020
00:35:33,120 --> 00:35:34,400
OTHER NEURONS THAT ARE

1021
00:35:34,400 --> 00:35:35,840
TASK-SPECIFIC.

1022
00:35:35,840 --> 00:35:37,600
SO WHAT DOES DO THEN?

1023
00:35:37,600 --> 00:35:39,360
THE DOWNSTREAM NEURON CAN LEARN

1024
00:35:39,360 --> 00:35:41,840
THE SET OF WEIGHTS TO ASSIGN TO

1025
00:35:41,840 --> 00:35:43,480
THE ACTIVITY OF THE MEDIAL

1026
00:35:43,480 --> 00:35:45,600
FRONTAL CORTICAL NEURONS AND

1027
00:35:45,600 --> 00:35:47,120
COMPUTE A WEIGHTED SUM TO

1028
00:35:47,120 --> 00:35:48,200
EXTRACT INFORMATION, A PROCESS

1029
00:35:48,200 --> 00:35:50,720
WE CAN MIMIC USING LINEAR --

1030
00:35:50,720 --> 00:35:53,000
SUCH AS SUPPORT VECTOR MACHINES

1031
00:35:53,000 --> 00:35:54,080
IN MOTION LEARNING.

1032
00:35:54,080 --> 00:35:56,080
WE SHOW WE CAN BUILD LINEAR

1033
00:35:56,080 --> 00:35:57,840
CLASSIFIERS TO DECODE CONFLICTS

1034
00:35:57,840 --> 00:35:59,280
AND ERRORS FROM THESE NEURONS

1035
00:35:59,280 --> 00:36:02,320
WITH GREATER THAN 90% ACCURACY

1036
00:36:02,320 --> 00:36:04,080
ACROSS BOTH TASKS.

1037
00:36:04,080 --> 00:36:05,600
THIS RESULT SHOWS THAT THE

1038
00:36:05,600 --> 00:36:09,760
MEDIAL FRONTAL CORTEX IS ABLE TO

1039
00:36:09,760 --> 00:36:10,600
SUPPORT PERFORMANCE MONITORING

1040
00:36:10,600 --> 00:36:15,240
IN A DOMAIN-GENERAL WAY, AND

1041
00:36:15,240 --> 00:36:16,840
IT'S CRITICAL FOR COGNITIVE

1042
00:36:16,840 --> 00:36:18,440
FLEXIBILITY AS WE NAVIGATE

1043
00:36:18,440 --> 00:36:19,640
THROUGH DIFFERENT TASKS IN OUR

1044
00:36:19,640 --> 00:36:20,880
DAILY LIFE.

1045
00:36:20,880 --> 00:36:22,080
I HOPE YOU WILL BE CHECKING OUT

1046
00:36:22,080 --> 00:36:23,640
OUR POSTER, WHERE YOU CAN FIND

1047
00:36:23,640 --> 00:36:24,520
MORE INFORMATION AND DETAILS

1048
00:36:24,520 --> 00:36:24,920
ABOUT THIS WORK.

1049
00:36:24,920 --> 00:36:26,840
THANK YOU SO MUCH FOR LISTENING.

1050
00:36:26,840 --> 00:36:27,680
>> HI.

1051
00:36:27,680 --> 00:36:30,520
MY NAME IS LANDON BAYLESS

1052
00:36:30,520 --> 00:36:33,520
EDWARDS, I'M AN MD PH.D. STUDENT

1053
00:36:33,520 --> 00:36:35,360
AT OREGON HEALTH AND SCIENCES

1054
00:36:35,360 --> 00:36:35,760
UNIVERSITY.

1055
00:36:35,760 --> 00:36:38,760
OUR LAB STUDIES HOW

1056
00:36:38,760 --> 00:36:40,040
NEUROMODULATORS SUCH AS

1057
00:36:40,040 --> 00:36:42,600
DOPAMINE, SAIR TOE NEN AND NOR

1058
00:36:42,600 --> 00:36:43,560
NOREPINEPHRINE ALLOW US TO DO

1059
00:36:43,560 --> 00:36:47,280
THINGS LIKE LOAK MOTOR, SOMETIME

1060
00:36:47,280 --> 00:36:49,360
LIE SUCH AS TASTE OR SMELL.

1061
00:36:49,360 --> 00:36:50,440
THESE NEUROMODULATORS SIGNAL BY

1062
00:36:50,440 --> 00:36:52,840
BINDING TO RECEPTORS ON NEURONS

1063
00:36:52,840 --> 00:36:54,840
CALLED G PROTEIN COUPLED

1064
00:36:54,840 --> 00:36:55,280
RECEPTORS.

1065
00:36:55,280 --> 00:36:56,600
ALTHOUGH THERE ARE HUNDREDS TO A

1066
00:36:56,600 --> 00:36:57,440
THOUSAND DIFFERENT TYPES OF

1067
00:36:57,440 --> 00:36:58,640
THESE RECEPTORS, THEY ALL

1068
00:36:58,640 --> 00:37:00,280
TRANSMIT A SIGNAL BY MODULATING

1069
00:37:00,280 --> 00:37:02,360
THE CONCENTRATION OF THE SMALL

1070
00:37:02,360 --> 00:37:06,080
MOLECULE CYCLIC AMP.

1071
00:37:06,080 --> 00:37:07,600
THEREFORE WE WISH TO VISUALIZE

1072
00:37:07,600 --> 00:37:09,360
THESE DYNAMICS IN VIVO AS A

1073
00:37:09,360 --> 00:37:10,920
READOUT OF NEUROMODULATORY

1074
00:37:10,920 --> 00:37:11,240
SIGNALING.

1075
00:37:11,240 --> 00:37:13,400
WE CAN THEN DETERMINE THE

1076
00:37:13,400 --> 00:37:14,720
NEUROMODULATORS AT PLAY BY

1077
00:37:14,720 --> 00:37:15,720
COMBINING THIS APPROACH WITH

1078
00:37:15,720 --> 00:37:17,320
PHARMACOLOGY.

1079
00:37:17,320 --> 00:37:20,400
TO DATE, APPROXIMATELY 80 CYCLIC

1080
00:37:20,400 --> 00:37:21,840
AMP SENSORS HAVE BEEN DEVELOPED,

1081
00:37:21,840 --> 00:37:23,040
HOWEVER, NONE OF THESE SENSORS

1082
00:37:23,040 --> 00:37:25,120
HAVE BEEN USED AT A SINGLE

1083
00:37:25,120 --> 00:37:26,640
NEURON RESOLUTION IN VIVO DUE TO

1084
00:37:26,640 --> 00:37:28,640
LIMITED DYNAMIC RANGE AND LOW

1085
00:37:28,640 --> 00:37:29,520
SENSITIVITY.

1086
00:37:29,520 --> 00:37:31,240
TO OVERCOME THESE OBSTACLES, WE

1087
00:37:31,240 --> 00:37:33,680
FIRST COMPARED A SUBSET OF

1088
00:37:33,680 --> 00:37:35,600
EXISTENT CYCLIC AMP SENSORS IN

1089
00:37:35,600 --> 00:37:36,360
IDENTICAL CONDITIONS.

1090
00:37:36,360 --> 00:37:39,120
THE MOST PROMISING SENSOR FOR

1091
00:37:39,120 --> 00:37:42,600
USE IN VIVO WAS H187 AS IT

1092
00:37:42,600 --> 00:37:44,040
ALREADY HAD A LARGE DYNAMIC

1093
00:37:44,040 --> 00:37:46,560
RANGE.

1094
00:37:46,560 --> 00:37:47,840
 -- TO IMPROVE UPON THE

1095
00:37:47,840 --> 00:37:49,600
SENSITIVITY AND SUBCELLULAR

1096
00:37:49,600 --> 00:37:50,480
DISTRIBUTION OF THIS SENSOR,

1097
00:37:50,480 --> 00:37:51,920
RESULTING IN A SERIES OF SENSORS

1098
00:37:51,920 --> 00:37:57,920
THAT WE CALLED CAMPFIRES, BASED

1099
00:37:57,920 --> 00:37:58,600
ON EPEC.

1100
00:37:58,600 --> 00:37:59,880
IN THE FIGURE ON THE BOTTOM

1101
00:37:59,880 --> 00:38:00,960
LEFT, I'M SHOWING A COMPARISON

1102
00:38:00,960 --> 00:38:03,400
OF A SUBSET OF PREVIOUSLY

1103
00:38:03,400 --> 00:38:04,480
PUBLISHED SENSORS COMPARED TO

1104
00:38:04,480 --> 00:38:06,360
THE CAMPFIRE SERIES.

1105
00:38:06,360 --> 00:38:10,720
WE APPLIED NOREPINEPHRINE AND

1106
00:38:10,720 --> 00:38:15,200
IBMX TO HEK293 CELLS THAT WERE

1107
00:38:15,200 --> 00:38:21,560
TRANSIENTLY EXPRESSING --

1108
00:38:21,560 --> 00:38:23,080
DYNAMIC RANGE RESPECTIVELY.

1109
00:38:23,080 --> 00:38:24,720
IN LIGHT BLUE HAVING THE HIGHEST

1110
00:38:24,720 --> 00:38:25,960
DYNAMIC RANGE.

1111
00:38:25,960 --> 00:38:28,360
YOU CAN SEE THAT THE CAMPFIRE

1112
00:38:28,360 --> 00:38:29,800
SENSORS SHOWN IN REDS AND ORANGE

1113
00:38:29,800 --> 00:38:30,880
HAVE INCREASED SENSITIVITY AND

1114
00:38:30,880 --> 00:38:32,840
ARE NAMED AS SUCH.

1115
00:38:32,840 --> 00:38:34,840
CAMPFIRE L LOWER SENSITIVITY, M

1116
00:38:34,840 --> 00:38:35,920
MEDIUM, AND H HIGH.

1117
00:38:35,920 --> 00:38:37,560
BUT THESE SENSORS ALL MAINTAIN

1118
00:38:37,560 --> 00:38:39,640
THE HIGH DYNAMIC RANGE OF THE

1119
00:38:39,640 --> 00:38:40,960
ORIGINAL EPAC SENSOR.

1120
00:38:40,960 --> 00:38:42,360
IN THE FIGURE ON THE BOTTOM

1121
00:38:42,360 --> 00:38:44,240
RIGHT, I'M SHOWING EXPRESSION OF

1122
00:38:44,240 --> 00:38:46,240
THE SENSOR IN NEURONS IN VIVO,

1123
00:38:46,240 --> 00:38:49,360
AND YOU CAN SEE THAT THE SENSOR

1124
00:38:49,360 --> 00:38:50,720
IS DISTRIBUTED DUE TO MUTATIONS

1125
00:38:50,720 --> 00:38:53,840
WE PUT IN THE NUCLEAR

1126
00:38:53,840 --> 00:38:54,720
LOCALIZATION MOTIF.

1127
00:38:54,720 --> 00:38:56,240
WE'VE SUCCESSFULLY USED THESE

1128
00:38:56,240 --> 00:38:59,520
SENSORS IN MULTIPLE PREPARATIONS

1129
00:38:59,520 --> 00:39:00,960
INCLUDING INCLUDE TOURED HIPPO

1130
00:39:00,960 --> 00:39:02,480
CAM PAP SLICES AND IN VIVO USING

1131
00:39:02,480 --> 00:39:07,320
A GRAIN WALL YAL         CRANIA.

1132
00:39:07,320 --> 00:39:09,840
IMPORTANTLY, LIFETIME IMAGING IS

1133
00:39:09,840 --> 00:39:10,880
IDEAL FOR USE IN VIVO.

1134
00:39:10,880 --> 00:39:11,880
WE'RE ABLE TO MEASURE

1135
00:39:11,880 --> 00:39:15,320
DIFFERENCES IN CYCLIC AMP LEVELS

1136
00:39:15,320 --> 00:39:15,920
IN -- AND DENDRITES.

1137
00:39:15,920 --> 00:39:17,160
YOU CAN ALSO SEE THIS IN THE

1138
00:39:17,160 --> 00:39:18,280
FIGURE ON THE BOTTOM RIGHT.

1139
00:39:18,280 --> 00:39:19,440
THIS IS PARTICULARLY IMPORTANT

1140
00:39:19,440 --> 00:39:22,080
FOR IMAGING OF CYCLIC AMP, AS

1141
00:39:22,080 --> 00:39:24,160
IT'S DIFFERENTIALLY REGULATED IN

1142
00:39:24,160 --> 00:39:25,000
DIFFERENT SUBCELLULAR

1143
00:39:25,000 --> 00:39:26,000
COMPARTMENTS.

1144
00:39:26,000 --> 00:39:29,400
WE'VE ALSO SHOWN BI-DIRECTIONAL

1145
00:39:29,400 --> 00:39:31,600
CYCLIC AMP DYNAMICS IN VIVO.

1146
00:39:31,600 --> 00:39:32,800
MY EXAMPLE ON THE RIGHT SHOWS

1147
00:39:32,800 --> 00:39:34,640
THIS CHANGE AS WELL, WHERE THE

1148
00:39:34,640 --> 00:39:36,400
CELLS ON THE TOP SHOW AN

1149
00:39:36,400 --> 00:39:39,240
INCREASE IN CYCLIC AMP

1150
00:39:39,240 --> 00:39:40,400
CONCENTRATION DURING RUNNING ON

1151
00:39:40,400 --> 00:39:41,880
THE RIGHT COMPARED TO BASELINE

1152
00:39:41,880 --> 00:39:42,400
ON THE LEFT.

1153
00:39:42,400 --> 00:39:44,080
THE CELLS ON THE BOTTOM SHOW A

1154
00:39:44,080 --> 00:39:47,440
DECREASE IN CYCLIC AMP IN

1155
00:39:47,440 --> 00:39:48,840
RUNNING COMPARED TO BASELINE ON

1156
00:39:48,840 --> 00:39:49,760
THE LEFT.

1157
00:39:49,760 --> 00:39:51,280
FINALLY, WE SHOWED A REDUCTION

1158
00:39:51,280 --> 00:39:54,320
IN CYCLIC AMP IN RESPONSE TO

1159
00:39:54,320 --> 00:39:55,760
SYSTEMIC OPIOID ADMINISTRATION.

1160
00:39:55,760 --> 00:39:57,680
ALTHOUGH THIS HAS BEEN SHOWN EX

1161
00:39:57,680 --> 00:40:00,680
VIVO AND IN VITRO, IT HAD YET TO

1162
00:40:00,680 --> 00:40:03,000
BE SHOWN IN VIVO.

1163
00:40:03,000 --> 00:40:03,840
THIS FINDING IN PARTICULAR IS

1164
00:40:03,840 --> 00:40:05,400
EXCITING TO ME BECAUSE IT'S THE

1165
00:40:05,400 --> 00:40:08,120
FOUNDATION FOR MY FUTURE

1166
00:40:08,120 --> 00:40:08,640
DISSERTATION WORK.

1167
00:40:08,640 --> 00:40:10,640
WE'RE EXCITED TO SHARE THESE

1168
00:40:10,640 --> 00:40:12,480
SENSORS WITH ANYONE INTERESTED

1169
00:40:12,480 --> 00:40:14,240
IN IMAGING NEUROMODULATORY EVENT

1170
00:40:14,240 --> 00:40:15,560
AND ARE WORKING WITH CLAB RAY

1171
00:40:15,560 --> 00:40:18,080
FORS TO GENERATE A MOUSE LINE TO

1172
00:40:18,080 --> 00:40:19,920
MAKE THESE SENSORS MORE WIDELY

1173
00:40:19,920 --> 00:40:20,240
ACCESSIBLE.

1174
00:40:20,240 --> 00:40:20,600
THANK YOU.

1175
00:40:20,600 --> 00:40:21,720
>> HI, EVERYONE.

1176
00:40:21,720 --> 00:40:27,040
MY I'M A POSTDOC AT UC BERKE LE.

1177
00:40:27,040 --> 00:40:29,640
THE WORK I WILL BE PRESENTING

1178
00:40:29,640 --> 00:40:34,920
TODAY IS DEVELOPMENT OF

1179
00:40:34,920 --> 00:40:40,960
MULTIPHOTON HOLE GRAPHIC

1180
00:40:40,960 --> 00:40:42,040
OPTOGENETICS THAT ESSENTIAL RI

1181
00:40:42,040 --> 00:40:44,440
ALLOWS YOU TO DO OPTOGENETIC

1182
00:40:44,440 --> 00:40:47,040
PERTURBATIONS WITH SINGLE CELL

1183
00:40:47,040 --> 00:40:47,680
SPATIAL PRECISION.

1184
00:40:47,680 --> 00:40:49,880
SO IN OTHER WORDS, INSTEAD OF

1185
00:40:49,880 --> 00:40:52,520
STIMULATION OF THE WHOLE GENETIC

1186
00:40:52,520 --> 00:40:53,200
REDEFINED POPULATION OF NEURONS

1187
00:40:53,200 --> 00:40:55,720
LIKE YOU WOULD DO WITH

1188
00:40:55,720 --> 00:40:57,000
CONVENTIONAL OPTOGENETICS, HERE

1189
00:40:57,000 --> 00:41:00,480
WE'RE ABLE TO SIMULATE TARGETED

1190
00:41:00,480 --> 00:41:02,560
FUNCTIONALLY DEFINED ENSEMBLES

1191
00:41:02,560 --> 00:41:04,760
THAT CAN BE INTERMINGLED

1192
00:41:04,760 --> 00:41:06,240
SPATIALLY.

1193
00:41:06,240 --> 00:41:07,440
SO WHAT WE DID IN THIS PROJECT

1194
00:41:07,440 --> 00:41:09,480
IS TO PUSH THE LIMITS IN TERMS

1195
00:41:09,480 --> 00:41:14,800
OF SPEED AND FIDELITY OF

1196
00:41:14,800 --> 00:41:15,160
READ-WRITES.

1197
00:41:15,160 --> 00:41:16,800
SO WE USED THIS NEW CONSTRUCT

1198
00:41:16,800 --> 00:41:24,240
WHICH COMBINES BOTH SUPER POTEN 

1199
00:41:24,240 --> 00:41:29,400
POTENT -- ME  ETF WITH MP # M.

1200
00:41:29,400 --> 00:41:31,680
WITH THIS NEW CONSTRUCT, WE WERE

1201
00:41:31,680 --> 00:41:35,760
ABLE TO WRITE IN OPTOGENETIC --

1202
00:41:35,760 --> 00:41:44,040
READ THEM OUT WITH HIGH

1203
00:41:44,040 --> 00:41:47,320
RESOLUTION, SO THE CHALLENGE

1204
00:41:47,320 --> 00:41:49,960
NOW -- PARADIGMS IN 3D IS THAT

1205
00:41:49,960 --> 00:41:53,800
YOU CAN'T USE TYPICAL

1206
00:41:53,800 --> 00:41:56,720
SEQUENTIAL -- WITH THE --

1207
00:41:56,720 --> 00:41:57,800
ACTUATOR, FOR INSTANCE, BECAUSE

1208
00:41:57,800 --> 00:41:59,000
THE FRAME RATE IN THAT CASE

1209
00:41:59,000 --> 00:42:02,200
WOULD BE DIVIDED BY THE NUMBER

1210
00:42:02,200 --> 00:42:03,080
OF -- YOU TAKE.

1211
00:42:03,080 --> 00:42:08,360
SO TO ADDRESS THIS, WE ADDRESSEE

1212
00:42:08,360 --> 00:42:11,360
GRAPHIC        HOLO

1213
00:42:11,360 --> 00:42:13,160
GRAPHIC MICROSCOPE AND ON THE

1214
00:42:13,160 --> 00:42:17,200
OTHER ARM HIGH SPEED VOL   VOLUC

1215
00:42:17,200 --> 00:42:18,640
VESSEL BEAM IMAGING.

1216
00:42:18,640 --> 00:42:23,120
VESSEL BEAMS ARE THESE

1217
00:42:23,120 --> 00:42:24,520
ACTUALLY -- POINT SPREAD

1218
00:42:24,520 --> 00:42:27,240
FUNCTIONS, WHICH ALLOW YOU TO

1219
00:42:27,240 --> 00:42:31,000
RECORD THE PROJECTION OF THE

1220
00:42:31,000 --> 00:42:32,520
FULL VOLUME ON TO A SINGLE

1221
00:42:32,520 --> 00:42:34,680
CLAIM, ESSENTIALLY GIVING YOU

1222
00:42:34,680 --> 00:42:40,080
VOLUMETRIC RECORDING, BUT AT

1223
00:42:40,080 --> 00:42:40,720
SINGLE FRAME RATE.

1224
00:42:40,720 --> 00:42:42,800
SO WE TESTED AND VALIDATED OUR

1225
00:42:42,800 --> 00:42:44,760
MICROSCOPE AND SHOW WE ARE ABLE

1226
00:42:44,760 --> 00:42:48,040
TO WRITE IN AND READ OUT THESE

1227
00:42:48,040 --> 00:42:50,440
HIGHLY STRUCTURED TRAINS IN

1228
00:42:50,440 --> 00:42:52,120
POPULATIONS OF NEURONS IN FULL

1229
00:42:52,120 --> 00:42:52,400
3D.

1230
00:42:52,400 --> 00:42:55,480
JUST A QUICK COMMENT ON THESE

1231
00:42:55,480 --> 00:42:56,840
FREQUENCIES WE NOW HAVE ACCESS

1232
00:42:56,840 --> 00:42:58,960
TO 10 HERTZ, 20 HERTZ, UP TO 30

1233
00:42:58,960 --> 00:43:04,800
HERTZ IN SOME CASES.

1234
00:43:04,800 --> 00:43:06,200
THIS IS PARTICULARLY RELEVANT

1235
00:43:06,200 --> 00:43:09,080
SINCE IF YOU TAKE, FOR INSTANCE,

1236
00:43:09,080 --> 00:43:11,240
MOUSE -- NEURONS IN VISUAL CORE

1237
00:43:11,240 --> 00:43:13,120
TECH, THEY FIRE AN AVERAGE

1238
00:43:13,120 --> 00:43:17,480
AROUND 10 HERTZ.

1239
00:43:17,480 --> 00:43:19,000
SO NOW WITH THIS LARGE SCALE

1240
00:43:19,000 --> 00:43:22,400
DATABASE OF HIGHLY STRUCTURED --

1241
00:43:22,400 --> 00:43:25,440
WITH KNOWN HOLOGRAPHIC RUN

1242
00:43:25,440 --> 00:43:27,880
THROUGH WE CAN BENCHMARK BUT

1243
00:43:27,880 --> 00:43:29,640
ALSO INFORM NEW SPIKE INFERENCE

1244
00:43:29,640 --> 00:43:32,800
MODELS FOR A MORE PRECISE --

1245
00:43:32,800 --> 00:43:35,440
SPIKE RATES AND SPIKE TIMES.

1246
00:43:35,440 --> 00:43:36,720
AND SOME OTHER EXCITING

1247
00:43:36,720 --> 00:43:38,800
EXPERIMENTS WE'RE DOING RIGHT

1248
00:43:38,800 --> 00:43:43,840
NOW THAT WE'RE PRESENTING VISUAL

1249
00:43:43,840 --> 00:43:46,440
STIMULI TO AWAKE MICE AND

1250
00:43:46,440 --> 00:43:47,920
ATTEMPT TO FAITHFULLY CREATE

1251
00:43:47,920 --> 00:43:49,320
THOSE VISUALLY EVOKED SPIKE

1252
00:43:49,320 --> 00:43:51,720
TRAINS WITH VERY HIGH PRECISION.

1253
00:43:51,720 --> 00:43:56,520
SO THIS METHOD REALLY HOPES THE

1254
00:43:56,520 --> 00:44:01,000
DOOR TO ULTRA SIZE CUSTOM

1255
00:44:01,000 --> 00:44:02,760
TAILORED CORTICAL PROSTHETICS.

1256
00:44:02,760 --> 00:44:04,640
THAT'S IT FOR ME.

1257
00:44:04,640 --> 00:44:05,600
I'M HAPPY TO SHOW YOU MORE OF

1258
00:44:05,600 --> 00:44:06,480
THIS ON MY POSTER.

1259
00:44:06,480 --> 00:44:07,840
THANK YOU FOR YOUR ATTENTION.

1260
00:44:07,840 --> 00:44:09,240
>> HELLO, EVERYONE.

1261
00:44:09,240 --> 00:44:11,720
MY NAME IS MOHAMMAD, I'M A PH.D.

1262
00:44:11,720 --> 00:44:16,760
CANDIDATE AT U.C. SAN DIEGO AND

1263
00:44:16,760 --> 00:44:18,080
RESEARCH ASSISTANT.

1264
00:44:18,080 --> 00:44:20,920
MEMORIES ARE STORED ACROSS

1265
00:44:20,920 --> 00:44:23,120
NEURAL CIRCUITS -- PASSING THE

1266
00:44:23,120 --> 00:44:24,320
INFORMATION FLOW ACROSS NEURAL

1267
00:44:24,320 --> 00:44:26,360
CIRCUITS AND ALLOW

1268
00:44:26,360 --> 00:44:27,720
COMMUNICATIONS BETWEEN PRE AND

1269
00:44:27,720 --> 00:44:29,800
POST SYNAPTIC SITES BY MEANS OF

1270
00:44:29,800 --> 00:44:33,040
SYNAPTIC STRENGTH.

1271
00:44:33,040 --> 00:44:33,800
DENDRITIC -- VOLUMES ARE KNOWN

1272
00:44:33,800 --> 00:44:36,240
TO HAVE HIGH CORRELATION THE

1273
00:44:36,240 --> 00:44:38,000
POST SYNAPTIC DENSITY AREA,

1274
00:44:38,000 --> 00:44:40,080
ACTIVE ZONES AREA AND SYNAPTIC

1275
00:44:40,080 --> 00:44:40,480
STRENGTH.

1276
00:44:40,480 --> 00:44:42,480
SO WE USE THE SPINE HEAD VOLUMES

1277
00:44:42,480 --> 00:44:44,880
AS THE SURROGATE OF SYNAPTIC

1278
00:44:44,880 --> 00:44:47,400
STRENGTH IN THIS PROJECT.

1279
00:44:47,400 --> 00:44:48,160
THE MOTIVATION BEHIND THIS

1280
00:44:48,160 --> 00:44:52,080
PROJECT IS THE OBSERVATION OF

1281
00:44:52,080 --> 00:44:56,560
SUBSTANTIAL LIABILITY IN SNAPS

1282
00:44:56,560 --> 00:44:57,680
SIZE ES THAT RAISE THIS

1283
00:44:57,680 --> 00:44:58,320
QUESTION.

1284
00:44:58,320 --> 00:45:01,960
HOW DOES THE BRAIN RETAIN STABLE

1285
00:45:01,960 --> 00:45:03,360
MEMORIES ACROSS NEURAL CIRCUITS

1286
00:45:03,360 --> 00:45:06,640
AND HOW DO WE LEARN NEW THINGS

1287
00:45:06,640 --> 00:45:08,480
DESPITE HIGH INHERENT DYNAMICS

1288
00:45:08,480 --> 00:45:10,160
OF SYNAPTIC STRENGTH.

1289
00:45:10,160 --> 00:45:12,640
WE BELIEVE IT HIGHLY DEPENDS ON

1290
00:45:12,640 --> 00:45:14,840
THE PRECISION OF SYNAPTIC

1291
00:45:14,840 --> 00:45:15,920
PLASTICITY.

1292
00:45:15,920 --> 00:45:17,880
TO FURTHER EXPLORE THIS

1293
00:45:17,880 --> 00:45:20,720
HYPOTHESIS, WE HAVE USED THREE

1294
00:45:20,720 --> 00:45:22,160
DIMENSIONAL RECONSTRUCTION OF

1295
00:45:22,160 --> 00:45:25,320
SERIAL SECTION ELECTROMICROSCOPY

1296
00:45:25,320 --> 00:45:26,440
THAT PROVIDES HIGH RESOLUTION

1297
00:45:26,440 --> 00:45:28,160
AND DETAILS OF PRE AND POST

1298
00:45:28,160 --> 00:45:30,480
SYNAPTIC MORPHOLOGY AND --

1299
00:45:30,480 --> 00:45:31,760
RESOURCES THAT IS NOT FEASIBLE

1300
00:45:31,760 --> 00:45:34,400
IN OTHER TECHNIQUES SUCH AS

1301
00:45:34,400 --> 00:45:35,760
LIGHT MICROSCOPY.

1302
00:45:35,760 --> 00:45:37,400
HERE IN THE TOP GRAPH, YOU SEE

1303
00:45:37,400 --> 00:45:40,720
THE LARGEST AND THE SMALLEST

1304
00:45:40,720 --> 00:45:42,840
SPINE HEAD VOLUMES MAINTAIN EACH

1305
00:45:42,840 --> 00:45:45,040
OF THE DATASETS AND THE RANGE OF

1306
00:45:45,040 --> 00:45:48,080
THEIR VOLUME IN THE ROLE

1307
00:45:48,080 --> 00:45:48,720
DENOTED.

1308
00:45:48,720 --> 00:45:49,880
THIS CLEARLY SHOWED THAT THE

1309
00:45:49,880 --> 00:45:52,040
INDUCTION OF LONG TERM

1310
00:45:52,040 --> 00:45:53,760
POTENTIATION EXPANDED THE RANGE

1311
00:45:53,760 --> 00:45:58,160
IN COMPARISON TO THE CONTROL --

1312
00:45:58,160 --> 00:45:59,560
FINALLY, IN THE BOTTOM FOUR

1313
00:45:59,560 --> 00:46:01,440
SUBPLOTS, YOU SEE THE NUMBER OF

1314
00:46:01,440 --> 00:46:04,640
DISTINGUISHABLEAPTIC

1315
00:46:04,640 --> 00:46:05,720
STRENGTH -- EACH OF THE FOUR

1316
00:46:05,720 --> 00:46:05,960
DATASETS.

1317
00:46:05,960 --> 00:46:07,720
AS YOU CAN SEE BY COMPARING

1318
00:46:07,720 --> 00:46:12,760
PANEL A TO C, 30 MINUTES AFTER

1319
00:46:12,760 --> 00:46:17,120
INDUCTION OF LTP, THE NUMBER OF

1320
00:46:17,120 --> 00:46:18,440
SYNAPTIC STRENGTH IS DOUBLED AND

1321
00:46:18,440 --> 00:46:19,920
SHOWN BY THE TWO HOURS POST

1322
00:46:19,920 --> 00:46:23,240
INDUCTION OF LTP, THEY STAYED

1323
00:46:23,240 --> 00:46:25,760
HIGHER THAN THE CONTROL CASES.

1324
00:46:25,760 --> 00:46:27,280
FURTHERMORE, OUR DIVERGENCE

1325
00:46:27,280 --> 00:46:28,800
ANALYSIS REVEALS THAT AT THE

1326
00:46:28,800 --> 00:46:31,440
TWO-HOUR POST INDUCTION OF LTP,

1327
00:46:31,440 --> 00:46:34,280
THE DISTRIBUTION OF CLUSTERS IS

1328
00:46:34,280 --> 00:46:38,760
MOVED CLOSER TO THE UNIFORM

1329
00:46:38,760 --> 00:46:39,880
DISTRIBUTION, IMPLYING EFFICIENT

1330
00:46:39,880 --> 00:46:43,240
CODING OCCURS AFTER LEARNING.

1331
00:46:43,240 --> 00:46:44,560
THANK YOU SO MUCH FOR YOUR TIME,

1332
00:46:44,560 --> 00:46:46,760
AND PLEASE COME TO MY POSTER FOR

1333
00:46:46,760 --> 00:46:49,160
FURTHER DISCUSSION.

1334
00:46:49,160 --> 00:46:50,120
>> HI.

1335
00:46:50,120 --> 00:46:52,640
MY NAME IS LUISA SHUSTER,

1336
00:46:52,640 --> 00:46:54,840
GRADUATE STUDENT AT NEW YORK

1337
00:46:54,840 --> 00:47:00,640
UNIVERSITY AND TODAY I WILL BE

1338
00:47:00,640 --> 00:47:03,600
DISCUSSING MY PROJECT OPEN

1339
00:47:03,600 --> 00:47:04,720
SOURCE HIGH-THROUGHPUT

1340
00:47:04,720 --> 00:47:06,120
MONITORING SYSTEM TO MATERNAL

1341
00:47:06,120 --> 00:47:08,400
BEHAVIOR MICE.

1342
00:47:08,400 --> 00:47:09,840
 -- CRUCIAL FOR THE SURVIVAL OF

1343
00:47:09,840 --> 00:47:10,280
SPECIES.

1344
00:47:10,280 --> 00:47:12,160
TYPICALLY THE FIRST SOCIAL

1345
00:47:12,160 --> 00:47:15,960
INTERACTION IN ANIMAL

1346
00:47:15,960 --> 00:47:16,600
EXPERIENCES.

1347
00:47:16,600 --> 00:47:18,400
 -- MAMMALS AND BECAUSE OF ITS

1348
00:47:18,400 --> 00:47:20,440
RICHNESS AND COMPLEXITY IN ORDER

1349
00:47:20,440 --> 00:47:24,600
TO UNDERSTAND ITS NEURAL

1350
00:47:24,600 --> 00:47:26,240
UNDERPINNINGS, NECESSARY TO

1351
00:47:26,240 --> 00:47:31,800
STUDY THESE INTERACTIONS

1352
00:47:31,800 --> 00:47:32,600
COMPREHENSIVELY.

1353
00:47:32,600 --> 00:47:36,000
TO ACHIEVE THIS, I DEVELOPED A

1354
00:47:36,000 --> 00:47:40,360
LOW COST OPEN SOURCE ENCLOSURE

1355
00:47:40,360 --> 00:47:45,160
TO LOOK AT THE NATURAL

1356
00:47:45,160 --> 00:47:47,800
PROJECTION OF MOTHERHOOD UP

1357
00:47:47,800 --> 00:47:49,560
UNTIL THREE TO FOUR CONSECUTIVE

1358
00:47:49,560 --> 00:47:53,920
ROUNDS OF BREEDING.

1359
00:47:53,920 --> 00:47:55,640
USING DIFFERENT SENSORS SUCH AS

1360
00:47:55,640 --> 00:47:58,720
CAMERAS, THERMAL SENSORS, IT

1361
00:47:58,720 --> 00:48:01,120
GIVES US INSIGHTS INTO THE

1362
00:48:01,120 --> 00:48:04,960
SECRET LIVES OF MICE AND HOW

1363
00:48:04,960 --> 00:48:07,800
THEY'RE INTERACTING WITH THEIR

1364
00:48:07,800 --> 00:48:13,080
THOUGHTS.

1365
00:48:13,080 --> 00:48:13,840
HOWEVER, THIS HAS BEEN USED FOR

1366
00:48:13,840 --> 00:48:15,800
THE TYPES OF SOCIAL INTERACTIONS

1367
00:48:15,800 --> 00:48:22,760
SUCH AS MALE/FEMALE --, ET

1368
00:48:22,760 --> 00:48:24,120
CETERA.

1369
00:48:24,120 --> 00:48:25,320
SOME OF THE THINGS WE'VE BEEN

1370
00:48:25,320 --> 00:48:30,560
ABLE TO FIND USING THIS APPROACH

1371
00:48:30,560 --> 00:48:32,520
THAT WE WOULD NOT HAVE BEEN ABLE

1372
00:48:32,520 --> 00:48:37,120
TO FIND HAD WE BEEN USING --

1373
00:48:37,120 --> 00:48:42,920
SUCH AS -- JUST A SNAPSHOT OF

1374
00:48:42,920 --> 00:48:47,960
PARENTAL BEHAVIORS IS THAT WHEN

1375
00:48:47,960 --> 00:48:52,880
WE ANALYZE THE -- OF ANIMALS

1376
00:48:52,880 --> 00:48:58,840
DURING PREGNANCY, WE NOTICE THAT

1377
00:48:58,840 --> 00:49:00,640
DEPENDING ON -- INTEGRITY SCORE

1378
00:49:00,640 --> 00:49:07,240
IF IT WAS LOW, -- MEANING THAT A

1379
00:49:07,240 --> 00:49:11,360
LOT OF PUPS COULD DIE.

1380
00:49:11,360 --> 00:49:14,280
HOWEVER, IF THE QUALITY SCORE

1381
00:49:14,280 --> 00:49:17,720
WAS HIGH, THE ANIMALS WERE

1382
00:49:17,720 --> 00:49:22,080
LIKELY TO SURVIVE POST -- UP TO

1383
00:49:22,080 --> 00:49:24,600
100%.

1384
00:49:24,600 --> 00:49:29,320
WE DECIDED TO LOOK TETHER MALL

1385
00:49:29,320 --> 00:49:31,040
PROPERTIES OF THIS NEST, HOW

1386
00:49:31,040 --> 00:49:32,800
THEY WERE CONTRIBUTING TO THE

1387
00:49:32,800 --> 00:49:35,560
WARMTH OF THE PUPS, AND WE SAW

1388
00:49:35,560 --> 00:49:41,120
THAT FEE SURES SUCH AS THE     A

1389
00:49:41,120 --> 00:49:42,320
WERE SUPER IMPORTANT IN

1390
00:49:42,320 --> 00:49:46,360
DETERMINING HOW -- A NEST IS,

1391
00:49:46,360 --> 00:49:48,480
EVEN THOUGH THE PUPS CANNOT

1392
00:49:48,480 --> 00:49:52,160
THERMOREGULATE AND THEY REQUIRE

1393
00:49:52,160 --> 00:49:53,640
CONSTANT INSULATION PROVIDED BY

1394
00:49:53,640 --> 00:49:55,880
THE MOM OR THE NEST AND THE MOM

1395
00:49:55,880 --> 00:49:57,160
MATES.

1396
00:49:57,160 --> 00:50:02,680
WITH MY PROJECT, I AM HOPING TO

1397
00:50:02,680 --> 00:50:06,160
LOWER THE -- BARRIERS -- EVEN

1398
00:50:06,160 --> 00:50:07,800
SOCIAL BEHAVIORS ARE VERY

1399
00:50:07,800 --> 00:50:09,240
EXPENSIVE TO STUDY.

1400
00:50:09,240 --> 00:50:12,280
>> HELLO, EVERYONE.

1401
00:50:12,280 --> 00:50:15,120
I AM A RESEARCH ASSOCIATE AT THE

1402
00:50:15,120 --> 00:50:16,760
BIOMEDICAL ENGINEERING

1403
00:50:16,760 --> 00:50:17,440
DEPARTMENT OF UNIVERSITY OF

1404
00:50:17,440 --> 00:50:19,480
SOUTHERN CALIFORNIA.

1405
00:50:19,480 --> 00:50:21,440
THANK THE NIH BRAIN INITIATIVE

1406
00:50:21,440 --> 00:50:22,680
FOR GIVING ME THIS GREAT

1407
00:50:22,680 --> 00:50:24,000
OPPORTUNITY TO SHARE SOME OF MY

1408
00:50:24,000 --> 00:50:27,920
WORKS WITH YOU.

1409
00:50:27,920 --> 00:50:29,680
COMMON MICRO ELECTRODE ARRAYS

1410
00:50:29,680 --> 00:50:31,440
ARE FLEXIBLE AND CAN GREATLY

1411
00:50:31,440 --> 00:50:33,720
REDUCE MECHANICAL MISMATCH

1412
00:50:33,720 --> 00:50:36,160
BETWEEN BRAIN TISSUE AND NEURAL

1413
00:50:36,160 --> 00:50:36,800
IMPLANT.

1414
00:50:36,800 --> 00:50:39,520
THIS MAKES IT A VERY PROMISING

1415
00:50:39,520 --> 00:50:40,840
TOOL FOR CHRONIC MONITOR AND

1416
00:50:40,840 --> 00:50:42,240
INTERFACING WITH NEURON TO

1417
00:50:42,240 --> 00:50:44,560
BETTER PROMOTE THE DEVELOPMENT

1418
00:50:44,560 --> 00:50:48,160
AND -- OF POLYMER MEAs.

1419
00:50:48,160 --> 00:50:50,080
WITH NIH'S SUPPORT, PROFESSOR

1420
00:50:50,080 --> 00:50:53,280
ALICE LONG AND PROFESSOR DONG

1421
00:50:53,280 --> 00:51:00,120
SONG LAUNCHED THE -- TO PROVIDE

1422
00:51:00,120 --> 00:51:00,520
NEUROSCIENCE AND

1423
00:51:00,520 --> 00:51:01,320
NEUROENGINEERING COMMUNITY WITH

1424
00:51:01,320 --> 00:51:03,480
AN EASY ACCESS TO FLEXIBLE

1425
00:51:03,480 --> 00:51:05,760
POLYMER MEAs TO GIVE

1426
00:51:05,760 --> 00:51:07,600
RESEARCHERS A CHOICE OF READY TO

1427
00:51:07,600 --> 00:51:12,000
USE POLYMER MEAs BY DESIGNING

1428
00:51:12,000 --> 00:51:14,080
A PENETRATING ARRAY -- WHICH CAN

1429
00:51:14,080 --> 00:51:16,040
BE USED TO RECORD FROM CORTICAL

1430
00:51:16,040 --> 00:51:17,800
AND SUBCORTICAL REGIONS OF

1431
00:51:17,800 --> 00:51:21,200
RODENT BRAINS.

1432
00:51:21,200 --> 00:51:25,360
THIS MEA HAS 64 ELECTRODES WITH

1433
00:51:25,360 --> 00:51:27,440
15 -- DIAMETERS TO OBTAIN NEURAL

1434
00:51:27,440 --> 00:51:29,640
RECORDINGS WITH SINGLE CELL

1435
00:51:29,640 --> 00:51:30,520
RESOLUTION.

1436
00:51:30,520 --> 00:51:31,920
CONSIDERING THE ANATOMY OF RAT

1437
00:51:31,920 --> 00:51:34,520
AND MICE BRAINS, THE MEA IS

1438
00:51:34,520 --> 00:51:39,040
DESIGNED TO HAVE -- SO THAT IT

1439
00:51:39,040 --> 00:51:42,320
CAN REACH SUBCORTICAL STRUCTURES

1440
00:51:42,320 --> 00:51:46,000
SUCH AS HIPPOCAMPUS.

1441
00:51:46,000 --> 00:51:48,200
WITH 350 MICRO METER SPACING

1442
00:51:48,200 --> 00:51:49,960
BETWEEN SHANKS, A RELATIVELY

1443
00:51:49,960 --> 00:51:52,680
LARGE BRAIN AREA OR MULTIPLE

1444
00:51:52,680 --> 00:51:54,840
CORTICAL REGIONS CAN BE COVERED

1445
00:51:54,840 --> 00:51:58,480
ON EACH SHANK, 16 ELECTRODES

1446
00:51:58,480 --> 00:52:00,440
WITH 120 MICRO METER SPACING BY

1447
00:52:00,440 --> 00:52:04,080
EVENLY DISTRIBUTED AT THE TIP

1448
00:52:04,080 --> 00:52:05,920
WITH 1.8-MILLIMETER RECORDING

1449
00:52:05,920 --> 00:52:08,120
RANGE, THE MEA CAN RECORD FROM

1450
00:52:08,120 --> 00:52:11,160
MULTIPLE LAYERS OF THE CORTEX OR

1451
00:52:11,160 --> 00:52:13,240
MULTIPLE LAYERS OF THE

1452
00:52:13,240 --> 00:52:15,320
HIPPOCAMPUS SIMULTANEOUSLY.

1453
00:52:15,320 --> 00:52:17,400
TO ASSIST THE IMPLANTATION OF

1454
00:52:17,400 --> 00:52:20,200
FLEXIBLE MEAs, I ALSO

1455
00:52:20,200 --> 00:52:23,200
DEVELOPED A VERY PRACTICAL

1456
00:52:23,200 --> 00:52:24,280
DEEP -- PRACTICAL PROTOCOL FOR

1457
00:52:24,280 --> 00:52:26,360
INSERTION OF THIS GENERIC

1458
00:52:26,360 --> 00:52:26,680
NEUROPROBE.

1459
00:52:26,680 --> 00:52:28,640
FOLLOWING THIS PROTOCOL, THE MEA

1460
00:52:28,640 --> 00:52:34,720
CAN BE TEMPORALLY -- BY A SINGLE

1461
00:52:34,720 --> 00:52:37,320
LAYER OF POLYETHYLENE -- WITH NO

1462
00:52:37,320 --> 00:52:41,240
SPECIFICALLY FABRICATED --

1463
00:52:41,240 --> 00:52:41,760
INVOLVED.

1464
00:52:41,760 --> 00:52:43,320
THIS PROTOCOL CAN GREATLY EASE

1465
00:52:43,320 --> 00:52:46,040
THE IMPLANTATION OF FLEXIBLE

1466
00:52:46,040 --> 00:52:46,800
MEAs.

1467
00:52:46,800 --> 00:52:51,000
TO TEST THE DURABILITY OF THE

1468
00:52:51,000 --> 00:52:52,040
COATING METHOD AND TO

1469
00:52:52,040 --> 00:52:53,760
CHARACTERIZE THE PERFORMANCE OF

1470
00:52:53,760 --> 00:52:58,200
THE POLYMER MEA, SIX PROBES

1471
00:52:58,200 --> 00:53:00,920
COATED WERE IMPLANTED INTO THE

1472
00:53:00,920 --> 00:53:01,600
RAT HIPPOCAMPUS.

1473
00:53:01,600 --> 00:53:03,880
ALL MEAs WERE SUCCESSFULLY

1474
00:53:03,880 --> 00:53:05,720
INSERTED INTO THE HIPPOCAMPUS,

1475
00:53:05,720 --> 00:53:09,120
AND RECORDED LOCAL FIELD

1476
00:53:09,120 --> 00:53:12,320
POTENTIALS SUCH AS -- WAVES AND

1477
00:53:12,320 --> 00:53:14,800
ACTIVITIES WITH SIGNAL TO NOISE

1478
00:53:14,800 --> 00:53:16,320
RATIO GREATER THAN 3.

1479
00:53:16,320 --> 00:53:18,960
FOR TWO ANIMALS, OVER 30 UNITS

1480
00:53:18,960 --> 00:53:20,720
WERE RECORDED FROM MULTIPLE

1481
00:53:20,720 --> 00:53:23,240
LAYERS OF THE RAT HIPPOCAMPUS ON

1482
00:53:23,240 --> 00:53:27,160
THE IMPLANTATION DAY.

1483
00:53:27,160 --> 00:53:29,040
PRELIMINARY EVALUATION OF THE

1484
00:53:29,040 --> 00:53:30,120
CHRONIC PERFORMANCE OF THE

1485
00:53:30,120 --> 00:53:33,760
POLYMER MEA WAS ALSO CONDUCTED.

1486
00:53:33,760 --> 00:53:36,800
HIGH AMPLITUDES, THETA WAVES AND

1487
00:53:36,800 --> 00:53:37,880
SPIKES WERE OBSERVED OVER A

1488
00:53:37,880 --> 00:53:41,920
PERIOD OF 37 DAYS.

1489
00:53:41,920 --> 00:53:43,800
AND THE SAME -- RECORDED UNITS

1490
00:53:43,800 --> 00:53:45,520
WAS SIMILAR WAVEFORMS OVER A

1491
00:53:45,520 --> 00:53:49,720
PERIOD OF 34 DAYS.

1492
00:53:49,720 --> 00:53:51,360
THESE PRELIMINARY EVALUATIONS

1493
00:53:51,360 --> 00:53:53,360
INDICATE THAT THIS GENERIC MEA

1494
00:53:53,360 --> 00:53:56,040
CAN SERVE A VALUABLE TOOL FOR

1495
00:53:56,040 --> 00:53:59,320
THE STUDY OF BRAIN FUNCTION.

1496
00:53:59,320 --> 00:54:00,640
THANKS A LOT FOR YOUR TIME AND

1497
00:54:00,640 --> 00:54:02,280
I'M MORE THAN HAPPY TO DISCUSS

1498
00:54:02,280 --> 00:54:03,480
ANY DETAIL DURING THE Q & A

1499
00:54:03,480 --> 00:54:06,040
SESSION.

1500
00:54:06,040 --> 00:54:06,880
>> HELLO.

1501
00:54:06,880 --> 00:54:10,600
MY NAME IS BEN, PH.D. CANDIDATE

1502
00:54:10,600 --> 00:54:11,880
AT JOHNS HOPKINS UNIVERSITY

1503
00:54:11,880 --> 00:54:15,200
WORKING IN JOSHUA VOGELSTEIN'S

1504
00:54:15,200 --> 00:54:15,400
LAB.

1505
00:54:15,400 --> 00:54:17,720
I WORK ON STATISTICAL AND

1506
00:54:17,720 --> 00:54:22,320
COMPUTATIONAL METHODS FOR MAPS

1507
00:54:22,320 --> 00:54:24,800
OF CONNECTIVITY.

1508
00:54:24,800 --> 00:54:27,640
HOW THE BRAIN CHANGES ACROSS

1509
00:54:27,640 --> 00:54:29,080
DEVELOPMENT, EVOLUTION,

1510
00:54:29,080 --> 00:54:30,960
EXPERIENCE, OR DISEASE STATE.

1511
00:54:30,960 --> 00:54:31,920
TO UNDERSTAND THESE PROPERTIES

1512
00:54:31,920 --> 00:54:33,680
AND HOW THEY RELATE TO NEURAL

1513
00:54:33,680 --> 00:54:34,760
WIRING, RESEARCHERS ARE

1514
00:54:34,760 --> 00:54:37,200
BEGINNING TO MAP MULTIPLE

1515
00:54:37,200 --> 00:54:38,680
ASSOCIATED CONNECTOMES, SAY FROM

1516
00:54:38,680 --> 00:54:40,320
TWO DIFFERENT RELATED SPECIES,

1517
00:54:40,320 --> 00:54:41,760
AND THEN COMPARE THESE

1518
00:54:41,760 --> 00:54:43,480
CONNECTOMES TO UNDERSTAND WHICH

1519
00:54:43,480 --> 00:54:44,720
ASPECTS OF NEURAL WIRING ARE

1520
00:54:44,720 --> 00:54:47,040
PRESERVED OR NOT.

1521
00:54:47,040 --> 00:54:49,760
MY WORK FOCUSES ON HOW TO MAKE

1522
00:54:49,760 --> 00:54:50,960
THESE ASSESSMENTS ONCE WE HAVE

1523
00:54:50,960 --> 00:54:51,720
THE DATA.

1524
00:54:51,720 --> 00:54:53,360
TWO MAPS OF NEURAL WIRING WILL

1525
00:54:53,360 --> 00:54:55,000
ALMOST NEVER BE IDENTICAL.

1526
00:54:55,000 --> 00:54:56,880
SO HOW CAN WE SAY WHETHER ANY

1527
00:54:56,880 --> 00:54:57,840
DIFFERENCES WE OBSERVE BETWEEN

1528
00:54:57,840 --> 00:55:01,160
THEM ARE MEANINGFUL?

1529
00:55:01,160 --> 00:55:03,640
AND WHAT DO WE EVEN MEAN BY

1530
00:55:03,640 --> 00:55:04,600
DIFFERENT FOR DIFFERENT

1531
00:55:04,600 --> 00:55:05,200
INTERCONNECTED NEURONS.

1532
00:55:05,200 --> 00:55:07,680
WE DEVELOPED A NEW METHODOLOGY

1533
00:55:07,680 --> 00:55:09,000
TO ANSWER THESE QUESTIONS BASED

1534
00:55:09,000 --> 00:55:10,440
ON BOTH WORK FROM NETWORK

1535
00:55:10,440 --> 00:55:11,640
SCIENCE WHICH STUDIES

1536
00:55:11,640 --> 00:55:12,640
CONNECTIVITY AND STATISTICS

1537
00:55:12,640 --> 00:55:14,240
WHICH STUDIES HOW TO MAKE CLAIMS

1538
00:55:14,240 --> 00:55:16,680
ABOUT WHETHER DIFFERENCES

1539
00:55:16,680 --> 00:55:17,760
BETWEEN TWO THINGS ARE MEANING

1540
00:55:17,760 --> 00:55:19,400
FU.

1541
00:55:19,400 --> 00:55:19,920
MEANINGFUL.

1542
00:55:19,920 --> 00:55:20,920
AN EXAMPLE OF THIS KIND OF

1543
00:55:20,920 --> 00:55:21,600
COMPARISON IS SHOWN TO THE

1544
00:55:21,600 --> 00:55:22,080
RIGHT.

1545
00:55:22,080 --> 00:55:23,600
HERE WE PLOT THE CONNECTIVITY OF

1546
00:55:23,600 --> 00:55:29,440
THE LECHT AND      LEFT AND RIGS

1547
00:55:29,440 --> 00:55:33,040
OF BRAIN OF A DROSOPHILA OR

1548
00:55:33,040 --> 00:55:37,200
VINEGAR FLY DURING ITS LARVAL

1549
00:55:37,200 --> 00:55:37,800
STAGE.

1550
00:55:37,800 --> 00:55:39,800
MORE IMPORTANTLY, WE DEVELOPED

1551
00:55:39,800 --> 00:55:47,040
STATISTICAL THEY MODS FOR METHO.

1552
00:55:47,040 --> 00:55:49,640
IN THE LARVA, WE FOUND SPECIFIC

1553
00:55:49,640 --> 00:55:51,600
NEURON TYPES DISPLAY DIFFERENT

1554
00:55:51,600 --> 00:55:53,200
CONNECTIVITY PATTERNS TWEAN THE

1555
00:55:53,200 --> 00:55:54,520
TWO BRAIN HEMISPHERE, BUT ALSO

1556
00:55:54,520 --> 00:55:56,160
THAT THIS DIFFERENCE GOES AWAY

1557
00:55:56,160 --> 00:55:57,720
IF ONE ONLY CONSIDERS THE

1558
00:55:57,720 --> 00:55:59,120
STRONGEST NEURAL CONNECTIONS.

1559
00:55:59,120 --> 00:56:00,760
THESE FINDINGS SUGGEST WHICH

1560
00:56:00,760 --> 00:56:02,160
PROPERTIES OF THE NEURAL WIRING

1561
00:56:02,160 --> 00:56:03,960
ARE IMPORTANT FOR THE GENOME TO

1562
00:56:03,960 --> 00:56:04,960
PRESERVE ON BOTH SIDES OF THE

1563
00:56:04,960 --> 00:56:08,760
BRAIN OF THIS ORGANISM.

1564
00:56:08,760 --> 00:56:10,400
AND WHILE OUR MORE RECENT WORK

1565
00:56:10,400 --> 00:56:12,800
APPLIED THESE TOOLS TO STUDY THE

1566
00:56:12,800 --> 00:56:14,440
BILATERAL SYMMETRY OF THE SINGLE

1567
00:56:14,440 --> 00:56:20,120
CONNECTOME, I'M IK SEATED      O

1568
00:56:20,120 --> 00:56:21,440
COMPARE OTHER CONNECTOMES IN A

1569
00:56:21,440 --> 00:56:22,320
PRINCIPAL WAY.

1570
00:56:22,320 --> 00:56:23,960
WHILE WE'RE STILL CONTINUING TO

1571
00:56:23,960 --> 00:56:25,160
EXPAND ON DIFFERENT NOTIONS

1572
00:56:25,160 --> 00:56:27,240
BETWEEN NETWORKS WHICH WE CAN

1573
00:56:27,240 --> 00:56:30,200
DETECT, WE EXPECT THIS FRAMEWORK

1574
00:56:30,200 --> 00:56:31,920
FOR STATISTICAL COMPARISON OF

1575
00:56:31,920 --> 00:56:33,920
CONNECTOMES WILL BE A AN

1576
00:56:33,920 --> 00:56:34,960
IMPORTANT COMPONENT TO INFORM

1577
00:56:34,960 --> 00:56:37,520
OUR IS   STUDY OF THE BRAIN.

1578
00:56:37,520 --> 00:56:38,360
SPECIFICALLY HOW NEURAL

1579
00:56:38,360 --> 00:56:39,560
CONNECTIVITY IS RELATED TO THE

1580
00:56:39,560 --> 00:56:42,200
MANY PROPERTIES I MENTIONED LIKE

1581
00:56:42,200 --> 00:56:43,560
DEVELOPMENT EVOLUTION,

1582
00:56:43,560 --> 00:56:45,840
EXPERIENCE, OR DISEASE STATE.

1583
00:56:45,840 --> 00:56:48,120
TO THAT END, WE'VE DEVELOPED

1584
00:56:48,120 --> 00:56:50,320
OPEN SOURCE PYTHON CODE TO

1585
00:56:50,320 --> 00:56:51,840
PERFORM ALL OF THESE ANALYSES

1586
00:56:51,840 --> 00:56:53,160
ALONG WITH ONLINE NOTEBOOKS TO

1587
00:56:53,160 --> 00:56:54,440
GUIDE RESEARCHERS THROUGH THE

1588
00:56:54,440 --> 00:56:56,560
PROCESS OF USING THIS CODE.

1589
00:56:56,560 --> 00:56:58,280
WE'RE ALWAYS HAPPY TO HAVE NEW

1590
00:56:58,280 --> 00:56:59,280
COLLABORATORS, SO PLEASE REACH

1591
00:56:59,280 --> 00:57:00,280
OUT IF ANY OF THIS IS

1592
00:57:00,280 --> 00:57:01,480
INTERESTING OR IF YOU HAVE

1593
00:57:01,480 --> 00:57:02,320
CONNECTOMES THAT YOU WANT TO

1594
00:57:02,320 --> 00:57:02,880
COMPARE.

1595
00:57:02,880 --> 00:57:07,080
THANK YOU.

1596
00:57:07,080 --> 00:57:08,920
>> WONDERFUL.

1597
00:57:08,920 --> 00:57:11,160
THANK YOU ALL, CONGRATULATIONS

1598
00:57:11,160 --> 00:57:13,160
AGAIN TO ALL OF OUR TRAVEL

1599
00:57:13,160 --> 00:57:14,760
AWARDEES IN THIS SESSION, AS

1600
00:57:14,760 --> 00:57:17,440
WELL AS THE OTHER CONCURRENT

1601
00:57:17,440 --> 00:57:18,760
SESSION THAT IS GOING ON.

1602
00:57:18,760 --> 00:57:20,280
THOSE WERE GREAT TALKS.

1603
00:57:20,280 --> 00:57:22,240
WE DO HAVE SOME QUESTIONS THAT

1604
00:57:22,240 --> 00:57:23,880
HAVE BEEN SUBMITTED THROUGH THE

1605
00:57:23,880 --> 00:57:25,840
Q & A FUNCTION AND WE'LL
JUST

1606
00:57:25,840 --> 00:57:27,280
REMIND OUR AUDIENCE THAT THERE

1607
00:57:27,280 --> 00:57:28,840
IS STILL TIME TO SUBMIT

1608
00:57:28,840 --> 00:57:30,240
QUESTIONS FOR ANY OF OUR

1609
00:57:30,240 --> 00:57:33,320
SPEAKERS TODAY.

1610
00:57:33,320 --> 00:57:34,440
WE WILL GO THROUGH THEM.

1611
00:57:34,440 --> 00:57:35,480
WE HAVE ABOUT 30 MINUTES OR SO

1612
00:57:35,480 --> 00:57:37,160
TO GET THROUGH QUESTIONS.

1613
00:57:37,160 --> 00:57:39,120
SO I'M JUST GOING TO GO AHEAD

1614
00:57:39,120 --> 00:57:42,160
AND START AND JAY AND I WILL

1615
00:57:42,160 --> 00:57:43,960
SORT OF TAG TEAM PRESENTING THE

1616
00:57:43,960 --> 00:57:46,920
QUESTIONS TO OUR SPEAKERS.

1617
00:57:46,920 --> 00:57:47,960
THE FIRST ONE WILL GO TO

1618
00:57:47,960 --> 00:57:50,520
DESIREE.

1619
00:57:50,520 --> 00:57:53,560
CAN DANCO GIVEN PERIPHERALLY AND

1620
00:57:53,560 --> 00:57:54,880
THEN UNCAGED LOCALLY IN THE

1621
00:57:54,880 --> 00:57:56,200
BRAIN OR MUST IT BE GIVEN

1622
00:57:56,200 --> 00:57:57,640
LOCALLY?

1623
00:57:57,640 --> 00:58:01,440
>> HI.

1624
00:58:01,440 --> 00:58:03,200
THANK YOU SO MUCH FOR YOUR

1625
00:58:03,200 --> 00:58:04,920
QUESTION.

1626
00:58:04,920 --> 00:58:05,680
DANCO IS A PEPTIDE.

1627
00:58:05,680 --> 00:58:07,560
BECAUSE OF THAT, IT'S SUBJECT TO

1628
00:58:07,560 --> 00:58:09,960
CLEARANCE BY PEPTIDASES SO IT

1629
00:58:09,960 --> 00:58:12,280
NEEDS TO BE GIVEN LOCALLY IN THE

1630
00:58:12,280 --> 00:58:12,800
BRAIN.

1631
00:58:12,800 --> 00:58:18,160
OTHER SMALL MOLECULE -- CAGED

1632
00:58:18,160 --> 00:58:20,560
SMALL MOLECULES SUCH AS THE

1633
00:58:20,560 --> 00:58:23,560
OXIES IS MORPHONE CAN BE GIVEN

1634
00:58:23,560 --> 00:58:25,960
SYSTEMICALLY AND UNCAGED LOCALLY

1635
00:58:25,960 --> 00:58:27,240
IN THE BRAIN REGION OF INTEREST,

1636
00:58:27,240 --> 00:58:29,360
AND IF YOU'RE INTERESTED IN

1637
00:58:29,360 --> 00:58:32,560
THAT, MY POSTER IS NUMBER 320

1638
00:58:32,560 --> 00:58:34,160
AND CAN YOU CHECK IT OUT.

1639
00:58:34,160 --> 00:58:36,440
BUT DANCO NEEDS TO BE

1640
00:58:36,440 --> 00:58:38,200
ADMINISTERED LOCALLY, YES.

1641
00:58:38,200 --> 00:58:39,720
>> THANKS FOR THAT,
DESIREE.

1642
00:58:39,720 --> 00:58:42,120
I'LL JUST MAKE A QUICK COMMENT.

1643
00:58:42,120 --> 00:58:44,120
THE BEST WAY THAT I CAN DESCRIBE

1644
00:58:44,120 --> 00:58:45,720
WHAT WE JUST HEARD IS, WOW!

1645
00:58:45,720 --> 00:58:47,520
I MEAN, THE DIVERSITY OF

1646
00:58:47,520 --> 00:58:48,920
SCIENCE, THE PERSPECTIVES, THE

1647
00:58:48,920 --> 00:58:50,280
EXPERIENCES FROM THE PANELISTS

1648
00:58:50,280 --> 00:58:52,640
THAT WE HEARD ABOUT, IT JUST

1649
00:58:52,640 --> 00:58:54,040
SUGGESTS THAT THE FUTURE OF

1650
00:58:54,040 --> 00:58:55,360
BIOMEDICAL RESEARCH IS LOOKING

1651
00:58:55,360 --> 00:58:55,920
HUGELY PROMISING.

1652
00:58:55,920 --> 00:58:57,680
SO AGAIN, CONGRATULATIONS TO ALL

1653
00:58:57,680 --> 00:58:58,640
OF YOU.

1654
00:58:58,640 --> 00:59:00,960
AS A REMINDER, FOR EVERYBODY

1655
00:59:00,960 --> 00:59:02,480
BEYOND OUR PANELISTS, ALL OF THE

1656
00:59:02,480 --> 00:59:03,680
RESEARCH HIGHLIGHTS YOU JUST

1657
00:59:03,680 --> 00:59:05,760
HEARD FROM ARE BEING PRESENTED

1658
00:59:05,760 --> 00:59:07,040
AS POSTERS AS WELL.

1659
00:59:07,040 --> 00:59:08,240
SOME OF THEM MAY HAVE BEEN

1660
00:59:08,240 --> 00:59:09,040
PRESENTED ALREADY, THERE ARE

1661
00:59:09,040 --> 00:59:10,560
MORE COMING, SO I ENCOURAGE YOU

1662
00:59:10,560 --> 00:59:12,280
TO VISIT THESE POSTERS AND HAVE

1663
00:59:12,280 --> 00:59:13,720
ADDITIONAL CONVERSATIONS WITH

1664
00:59:13,720 --> 00:59:14,360
PRESENTERS.

1665
00:59:14,360 --> 00:59:16,040
I'LL SAY THAT I'VE GOT GENERALLY

1666
00:59:16,040 --> 00:59:17,320
TWO BUCKETS OF QUESTIONS.

1667
00:59:17,320 --> 00:59:18,680
ONE ARE SOME VERY SPECIFIC

1668
00:59:18,680 --> 00:59:20,520
RESEARCH QUESTIONS THAT PEOPLE

1669
00:59:20,520 --> 00:59:21,720
HAVE SUBMITTED AND WE WILL COVER

1670
00:59:21,720 --> 00:59:23,360
AS MANY OF THESE AS WE CAN, AND

1671
00:59:23,360 --> 00:59:24,920
THERE'S ANOTHER GENERAL BUCKET

1672
00:59:24,920 --> 00:59:26,440
OF SORT OF JUST LIFE

1673
00:59:26,440 --> 00:59:27,640
EXPERIENCES, PARTICULARLY AT

1674
00:59:27,640 --> 00:59:29,280
YOUR CAREER STAGE.

1675
00:59:29,280 --> 00:59:31,000
SO WE OPEN THIS UP TO ALL

1676
00:59:31,000 --> 00:59:32,120
PANELISTS IF YOU HAVE SOMETHING

1677
00:59:32,120 --> 00:59:32,760
TO SAY.

1678
00:59:32,760 --> 00:59:34,200
BUT WITH THAT, I'LL JUMP INTO

1679
00:59:34,200 --> 00:59:35,800
ONE OF THE QUESTIONS THAT WE DID

1680
00:59:35,800 --> 00:59:36,640
RECEIVE.

1681
00:59:36,640 --> 00:59:40,080
THIS ONE IS FOR HUNYUN SHIN,

1682
00:59:40,080 --> 00:59:42,000
HAVE YOU DONE ANY BEHAVIORAL TWO

1683
00:59:42,000 --> 00:59:44,280
CHOICE TASK BETWEEN THE ILLUSORY

1684
00:59:44,280 --> 00:59:45,560
CONTOUR AND THE PROBE CONTOURS

1685
00:59:45,560 --> 00:59:47,880
TO SEE IF THE ILLUSION

1686
00:59:47,880 --> 00:59:49,840
PERCEPTION HOLDS BEHAVIOR --

1687
00:59:49,840 --> 00:59:50,880
HOLDS IN BEHAVIOR?

1688
00:59:50,880 --> 00:59:51,920
>> YES, THANK YOU FOR THE

1689
00:59:51,920 --> 00:59:53,760
QUESTION AND SORRY I DIDN'T

1690
00:59:53,760 --> 00:59:57,360
COVER THE PRIOR LITERATURE, BUT

1691
00:59:57,360 --> 00:59:59,000
THERE HAS BEEN TWO PRIOR STUDIES

1692
00:59:59,000 --> 01:00:03,400
USING MICE, USING ALTERNATIVE

1693
01:00:03,400 --> 01:00:07,120
POOR CHOICE BEHAVIOR SHOWING

1694
01:00:07,120 --> 01:00:13,200
MILES CAN -- I LEWIS     ILLUSOD

1695
01:00:13,200 --> 01:00:14,560
VICE VERSA SO THEY CAN BE

1696
01:00:14,560 --> 01:00:15,840
PERCEIVED BY MICE.

1697
01:00:15,840 --> 01:00:18,080
SO BUILDING UPON THAT, OUR STUDY

1698
01:00:18,080 --> 01:00:21,840
FOCUSED ON THE REPRESENTATION

1699
01:00:21,840 --> 01:00:23,520
INDIVIDUAL PROTECTION ESPECIALLY

1700
01:00:23,520 --> 01:00:25,320
FOR HIGHER VISUAL AREAS, THIS IS

1701
01:00:25,320 --> 01:00:26,920
THE FIRST STUDY TO LOOK AT

1702
01:00:26,920 --> 01:00:28,200
HIGHER VISUAL AREA

1703
01:00:28,200 --> 01:00:32,280
REPRESENTATION IN MICE.

1704
01:00:32,280 --> 01:00:33,840
>> I HAVE A QUICK
FOLLOW-UP

1705
01:00:33,840 --> 01:00:34,560
QUESTION FOR YOU AS WELL.

1706
01:00:34,560 --> 01:00:35,760
YOU MAY HAVE SAID THIS BUT I

1707
01:00:35,760 --> 01:00:37,080
MISSED IT.

1708
01:00:37,080 --> 01:00:40,400
WHAT AGES ARE YOU TESTING AND IS

1709
01:00:40,400 --> 01:00:42,200
THERE SOME PREDICTABLE

1710
01:00:42,200 --> 01:00:44,160
FUNCTIONAL PATTERNS IN TERMS OF

1711
01:00:44,160 --> 01:00:45,480
DEVELOPMENT WHEN THESE SYSTEMS

1712
01:00:45,480 --> 01:00:45,840
COME ONLINE?

1713
01:00:45,840 --> 01:00:47,600
>> THAT'S A GREAT
QUESTION, ONE

1714
01:00:47,600 --> 01:00:48,880
THAT I CANNOT ADDRESS.

1715
01:00:48,880 --> 01:00:54,040
SO I'M JUST USING ADULT MICE AND

1716
01:00:54,040 --> 01:00:55,280
I HAVEN'T LOOKED AT --

1717
01:00:55,280 --> 01:00:56,000
DEVELOPMENT.

1718
01:00:56,000 --> 01:00:58,320
BUT YEAH, IT'S LEARNING AND

1719
01:00:58,320 --> 01:01:01,040
EXPERIENCES IS IMPORTANT FOR

1720
01:01:01,040 --> 01:01:01,920
PERCEIVING THE SOLUTION, YOU

1721
01:01:01,920 --> 01:01:04,640
WOULD THINK THAT WOULD CHANGE --

1722
01:01:04,640 --> 01:01:05,760
DEVELOPMENT SO THAT WOULD BE A

1723
01:01:05,760 --> 01:01:07,080
FUTURE AVENUE.

1724
01:01:07,080 --> 01:01:11,200
>> SOUNDS GOOD.

1725
01:01:11,200 --> 01:01:14,160
THIS ONE IS FOR MICHELLE.

1726
01:01:14,160 --> 01:01:16,240
WHAT ARE YOU USING TO DELIVER

1727
01:01:16,240 --> 01:01:18,440
THE JEDI-2P INTO THE BRAIN?

1728
01:01:18,440 --> 01:01:20,720
IS IT AAVs, CAN THEY BE

1729
01:01:20,720 --> 01:01:22,600
TARGETED TO SPECIFIC CELL TYPES?

1730
01:01:22,600 --> 01:01:25,520
>> GREAT QUESTION.

1731
01:01:25,520 --> 01:01:27,080
YEAH, THAT'S ONE OF THE BEAUTIES

1732
01:01:27,080 --> 01:01:29,600
OF GENETICALLY ENCODABLE

1733
01:01:29,600 --> 01:01:31,760
INDICATORS, THEY'RE ENTIRELY

1734
01:01:31,760 --> 01:01:33,400
GENETICALLY ENCODED SO YES, WE

1735
01:01:33,400 --> 01:01:35,240
USE AAVs TO GET THEM WHERE

1736
01:01:35,240 --> 01:01:35,840
THEY SHOULD BE.

1737
01:01:35,840 --> 01:01:37,880
WE HAVE MANY DIFFERENT

1738
01:01:37,880 --> 01:01:38,920
PROMOTERS, SO ONE OF THE ONES

1739
01:01:38,920 --> 01:01:43,160
THAT YOU PROBABLY SAW, SHOUT OUT

1740
01:01:43,160 --> 01:01:46,760
FOR THAT BEAUTIFUL DATA, IS A

1741
01:01:46,760 --> 01:01:48,280
KREE-DEPENDENT ONE THAT WE HAD

1742
01:01:48,280 --> 01:01:53,640
FOR EF1 ALPHA, AND BASICALLY --

1743
01:01:53,640 --> 01:01:56,040
SO WE HAVE CRE-DEPENDENT PLA

1744
01:01:56,040 --> 01:01:57,480
MASS, WE HAVE PROMOTERS THAT CAN

1745
01:01:57,480 --> 01:01:59,880
BE JUST NEURONAL SPECIFIC LIKE

1746
01:01:59,880 --> 01:02:02,800
HCIN, OR WE CAN DO SOMETHING

1747
01:02:02,800 --> 01:02:10,520
LIKE IM.   GLUTAMATERGIC OR CELL

1748
01:02:10,520 --> 01:02:11,680
EXPRESSION.

1749
01:02:11,680 --> 01:02:14,320
NON-RODENT MODELS AS WELL LIKE

1750
01:02:14,320 --> 01:02:14,760
FLEAS.

1751
01:02:14,760 --> 01:02:17,280
IF YOU'RE INTERESTED, GO TO MY

1752
01:02:17,280 --> 01:02:19,440
POSTER, 814, AND WE HAVE SOME

1753
01:02:19,440 --> 01:02:23,840
WAYS TO CONTACT US THERE.

1754
01:02:23,840 --> 01:02:25,600
>> THANKS FOR THAT,
MICHELLE.

1755
01:02:25,600 --> 01:02:27,040
I THINK ANYBODY WOULD WANT TO GO

1756
01:02:27,040 --> 01:02:29,760
HEAR MORE ABOUT JEDIs, OR THE

1757
01:02:29,760 --> 01:02:30,720
LAST OR MAYBE NOT THE LAST AS

1758
01:02:30,720 --> 01:02:31,720
WELL.

1759
01:02:31,720 --> 01:02:33,040
SO VERY CREATIVE.

1760
01:02:33,040 --> 01:02:33,480
NICE JOB.

1761
01:02:33,480 --> 01:02:34,560
SO WE HAVE ANOTHER QUESTION THAT

1762
01:02:34,560 --> 01:02:35,200
CAME IN.

1763
01:02:35,200 --> 01:02:37,320
THIS ONE IS FOR LANDON.

1764
01:02:37,320 --> 01:02:40,240
THE QUESTION IS, IS CAMPFIRE

1765
01:02:40,240 --> 01:02:41,760
COMPATIBLE FOR COIMAGING WITH

1766
01:02:41,760 --> 01:02:42,480
CALCIUM IMAGING?

1767
01:02:42,480 --> 01:02:43,560
>> YEAH, THAT'S A GREAT

1768
01:02:43,560 --> 01:02:43,960
QUESTION.

1769
01:02:43,960 --> 01:02:45,960
THERE IS POTENTIAL COMPATIBILITY

1770
01:02:45,960 --> 01:02:46,360
THERE.

1771
01:02:46,360 --> 01:02:47,480
THIS IS SOMETHING WE HAVEN'T

1772
01:02:47,480 --> 01:02:48,680
DONE YET, BUT IT'S SOMETHING

1773
01:02:48,680 --> 01:02:50,080
WE'RE PLANNING TO DO.

1774
01:02:50,080 --> 01:02:52,760
ONE OF THE BENEFITS OF CAMPFIRES

1775
01:02:52,760 --> 01:02:54,560
IS THAT THEY'RE COMPATIBLE WITH

1776
01:02:54,560 --> 01:02:56,000
FLUORESCENCE LIFETIME IMAGING,

1777
01:02:56,000 --> 01:02:57,200
SO THIS FREES UP A CHANNEL THAT

1778
01:02:57,200 --> 01:02:58,720
COULD BE USED, FOR EXAMPLE, WITH

1779
01:02:58,720 --> 01:03:02,880
A RED CALCIUM SENSOR.

1780
01:03:02,880 --> 01:03:04,680
>> SOUNDS GOOD.

1781
01:03:04,680 --> 01:03:07,600
I HAVE A QUESTION FOR NATALIE.

1782
01:03:07,600 --> 01:03:08,880
I JUST COULDN'T SEE THE SLIDE

1783
01:03:08,880 --> 01:03:13,160
VERY WELL SO THIS IS FOR MY OWN

1784
01:03:13,160 --> 01:03:15,680
CLARIFICATION.

1785
01:03:15,680 --> 01:03:17,560
WHAT WAS THE SCALE ON THE OXYGEN

1786
01:03:17,560 --> 01:03:20,600
CONSUMPTION WHERE YOU FIRST

1787
01:03:20,600 --> 01:03:21,920
NOTED THAT LAYER ONE WAS THE

1788
01:03:21,920 --> 01:03:23,440
HIGHEST IN TERMS OF OXYGEN

1789
01:03:23,440 --> 01:03:24,320
CONSUMPTION COMPARED TO LAYER

1790
01:03:24,320 --> 01:03:25,840
FOUR, WHICH WAS WHERE WE MIGHT

1791
01:03:25,840 --> 01:03:29,880
PREDICT TO BE SO, WHAT WAS THE

1792
01:03:29,880 --> 01:03:31,040
SCALE BETWEEN THE TWO?

1793
01:03:31,040 --> 01:03:34,400
>> IT WAS LIKE DOUBLE.

1794
01:03:34,400 --> 01:03:36,120
SO IN LAYER ONE, WE HAD DOUBLE

1795
01:03:36,120 --> 01:03:37,880
MORE OXYGEN CONSUMPTION.

1796
01:03:37,880 --> 01:03:41,600
>> AND CAN YOU -- WHAT'S
YOUR

1797
01:03:41,600 --> 01:03:42,800
BEST GUESS AS TO WHY WE'RE

1798
01:03:42,800 --> 01:03:47,520
SEEING THIS IN LAYER ONE?

1799
01:03:47,520 --> 01:03:49,800
>> NOT MANY CELL BODIES,
THERE

1800
01:03:49,800 --> 01:03:54,840
ARE A LOT OF DENDRITES AND WE

1801
01:03:54,840 --> 01:03:57,160
THINK DENDRITIC COMPUTATIONS

1802
01:03:57,160 --> 01:03:58,200
COST A LOT OF ENERGY.

1803
01:03:58,200 --> 01:03:59,880
SO THERE ARE LONG-RANGE

1804
01:03:59,880 --> 01:04:01,040
CONNECTIONS BETWEEN CORTICAL

1805
01:04:01,040 --> 01:04:05,880
AREAS, BUTS ARE ASCENDING

1806
01:04:05,880 --> 01:04:07,640
CONNECTIONS FROM BASAL

1807
01:04:07,640 --> 01:04:09,280
FOREBRAIN, CHOLINERGIC FIBERS

1808
01:04:09,280 --> 01:04:12,880
COME THERE FROM THE -- SO THERE

1809
01:04:12,880 --> 01:04:16,080
ARE MANY INTERCONNECTIONS GOING

1810
01:04:16,080 --> 01:04:23,360
ON, AND ALL -- THEY ARE 45, BUT

1811
01:04:23,360 --> 01:04:24,920
FOUR-FIVE BUT THEY PROJECT TO

1812
01:04:24,920 --> 01:04:25,800
LAYER ONE AND HAVE THIS

1813
01:04:25,800 --> 01:04:27,200
BEAUTIFUL TREE, SO WE THINK THIS

1814
01:04:27,200 --> 01:04:28,400
COSTS A LOT OF ENERGY.

1815
01:04:28,400 --> 01:04:32,440
BUT IN ADDITION, ONE THING TO

1816
01:04:32,440 --> 01:04:35,400
KEEP IN MIND IS THAT WHAT WE SEE

1817
01:04:35,400 --> 01:04:37,720
IS TRUE, MIGHT BE TRUE, HOWEVER,

1818
01:04:37,720 --> 01:04:39,480
UNDER CERTAIN CONDITIONS, LET'S

1819
01:04:39,480 --> 01:04:41,240
SAY UNDER DRASTIC CONDITIONS

1820
01:04:41,240 --> 01:04:46,480
WHEN OXYGEN LEVELS SINK -- OR

1821
01:04:46,480 --> 01:04:48,080
MAYBE DURING AGING WHEN OXYGEN

1822
01:04:48,080 --> 01:04:51,360
DELIVERY ISN'T AS EFFICIENT AS

1823
01:04:51,360 --> 01:04:52,360
IN YOUNG STATES, IT MIGHT BE

1824
01:04:52,360 --> 01:04:55,320
IMPORTANT TO HAVE HIGHER

1825
01:04:55,320 --> 01:04:56,080
MITOCHONDRIAL DENSITY AND

1826
01:04:56,080 --> 01:04:57,760
THEREFORE TO EXTRACT OXYGEN

1827
01:04:57,760 --> 01:04:58,080
BETTER.

1828
01:04:58,080 --> 01:04:59,040
THIS IS ONE IDEA.

1829
01:04:59,040 --> 01:05:01,200
BUT THIS IS SOMETHING THAT CAN

1830
01:05:01,200 --> 01:05:02,760
BE STUDIED FURTHER.

1831
01:05:02,760 --> 01:05:04,600
BUT IT'S DEFINITELY NOT JUST

1832
01:05:04,600 --> 01:05:07,120
UNDER RESTING CONDITION.

1833
01:05:07,120 --> 01:05:07,600
>> VERY GOOD.

1834
01:05:07,600 --> 01:05:10,640
THANK YOU.

1835
01:05:10,640 --> 01:05:14,440
WE ALSO HAVE A QUESTION FOR

1836
01:05:14,440 --> 01:05:15,120
CARLOS.

1837
01:05:15,120 --> 01:05:16,520
IF YOU DISRUPT THE AUDITORY

1838
01:05:16,520 --> 01:05:17,640
PROJECTING NEURONS DURING THE

1839
01:05:17,640 --> 01:05:21,480
LEARNING PHASE, DO THEY NOT

1840
01:05:21,480 --> 01:05:22,280
LEARN THE SONGS?

1841
01:05:22,280 --> 01:05:24,640
>> THANK YOU FOR THAT
QUESTION.

1842
01:05:24,640 --> 01:05:26,840
SO RECENT WORK HAS SHOWN IF YOU

1843
01:05:26,840 --> 01:05:31,840
USE CRE-DEPENDENT -- ONLY THE

1844
01:05:31,840 --> 01:05:34,160
AUDITORY PROJECTING NEURONS

1845
01:05:34,160 --> 01:05:35,680
DURING THE LEARNING PHASE

1846
01:05:35,680 --> 01:05:36,560
SPECIFICALLY THEY WILL NOT LEARN

1847
01:05:36,560 --> 01:05:37,320
THEIR SONG.

1848
01:05:37,320 --> 01:05:38,200
THE DEGREE OF LEARNING

1849
01:05:38,200 --> 01:05:39,680
CORRELATES WITH THE AMOUNT OF

1850
01:05:39,680 --> 01:05:43,320
LESIONS, SO MORE CELLS --

1851
01:05:43,320 --> 01:05:44,880
PROJECTED TO THE AUDITORY

1852
01:05:44,880 --> 01:05:46,200
REGION, A DECREASED AMOUNT OF

1853
01:05:46,200 --> 01:05:46,640
LEARNING.

1854
01:05:46,640 --> 01:05:48,480
BUT IF YOU DO THIS IN THE ADULT

1855
01:05:48,480 --> 01:05:50,120
BIRDS WHEN THEY HAVE ALREADY

1856
01:05:50,120 --> 01:05:51,240
LEARNED THEIR SONG, IT WILL HAVE

1857
01:05:51,240 --> 01:05:52,640
NO AFFECT ON THEIR SONG.

1858
01:05:52,640 --> 01:05:54,600
SO THIS WORK ALSO HIGHLIGHTS THE

1859
01:05:54,600 --> 01:05:57,440
IMPORTANCE OF THESE SPECIFIC

1860
01:05:57,440 --> 01:05:59,720
CELL TYPES AT A PARTICULAR TIME

1861
01:05:59,720 --> 01:06:03,920
POINT IN DEVELOPMENT.

1862
01:06:03,920 --> 01:06:07,600
>> OKAY, THANK YOU,
CARLOS.

1863
01:06:07,600 --> 01:06:08,160
LET'S SEE.

1864
01:06:08,160 --> 01:06:10,000
I'M GOING TO JUMP INTO ONE OF MY

1865
01:06:10,000 --> 01:06:11,120
OWN QUESTIONS I ACTUALLY HAVE

1866
01:06:11,120 --> 01:06:12,200
HERE, AND I WANT TO OPEN THIS UP

1867
01:06:12,200 --> 01:06:13,080
TO THE PANELISTS.

1868
01:06:13,080 --> 01:06:14,400
WE'RE GOING TO COME BACK TO SOME

1869
01:06:14,400 --> 01:06:15,320
MORE SPECIFIC SCIENCE QUESTIONS.

1870
01:06:15,320 --> 01:06:19,080
WITH YOU I'M      BUT I'M REALLN

1871
01:06:19,080 --> 01:06:20,000
HEARING FROM THE PANELISTS AND

1872
01:06:20,000 --> 01:06:21,840
HAVING YOU SHARE YOUR

1873
01:06:21,840 --> 01:06:22,280
EXPERIENCES.

1874
01:06:22,280 --> 01:06:23,480
WE'VE ALL JUST GONE THROUGH

1875
01:06:23,480 --> 01:06:24,360
WHERE WE'RE GOING THROUGH THIS

1876
01:06:24,360 --> 01:06:25,680
THING WE CALL COVID, WHICH WE

1877
01:06:25,680 --> 01:06:27,240
COULD HAVE NEVER ANTICIPATED,

1878
01:06:27,240 --> 01:06:29,680
AND IT HAS HAD AN ABSOLUTE

1879
01:06:29,680 --> 01:06:32,120
IMPACT ON OUR LIVES, ON OUR

1880
01:06:32,120 --> 01:06:35,080
ABILITY TO DO SCIENCE,

1881
01:06:35,080 --> 01:06:36,360
PARTICULARLY FOR PEOPLE ON THE

1882
01:06:36,360 --> 01:06:37,800
PANEL HERE WHO ARE AT VERY

1883
01:06:37,800 --> 01:06:39,360
CRITICAL STAGES IN THEIR CAREER

1884
01:06:39,360 --> 01:06:39,760
DEVELOPMENT.

1885
01:06:39,760 --> 01:06:41,520
SO I'M CURIOUS IF YOU CAN OFFER

1886
01:06:41,520 --> 01:06:43,600
SOME OF WHAT YOU HAVE DONE FROM

1887
01:06:43,600 --> 01:06:46,440
A STRATEGIC PERSPECTIVE TO

1888
01:06:46,440 --> 01:06:47,120
REMAIN PRODUCTIVE, TO CONTINUE

1889
01:06:47,120 --> 01:06:49,280
TO MOVE FORWARD AND NOT JUST TO

1890
01:06:49,280 --> 01:06:52,360
STOP WHERE YOU'RE AT.

1891
01:06:52,360 --> 01:06:54,440
I THINK OTHERS WOULD BE REALLY

1892
01:06:54,440 --> 01:06:55,760
INTERESTED TO HEAR WHAT SOME OF

1893
01:06:55,760 --> 01:06:58,480
THOSE THINGS HAVE BEEN.

1894
01:06:58,480 --> 01:07:01,320
AND THAT'S OPEN TO ANYBODY.

1895
01:07:01,320 --> 01:07:03,880
>> I CAN START.

1896
01:07:03,880 --> 01:07:08,320
SO AS YOU KNOW, I DO

1897
01:07:08,320 --> 01:07:09,960
24/7 RECORDING, SO BEHAVIOR

1898
01:07:09,960 --> 01:07:11,400
ACROSS CONSECUTIVE -- SO WHEN

1899
01:07:11,400 --> 01:07:13,920
THE PANDEMIC STARTED AND WE -- I

1900
01:07:13,920 --> 01:07:15,880
HAD TO STOP EXPERIMENTS SO THAT

1901
01:07:15,880 --> 01:07:18,800
ACTUALLY INSPIRED ME TO DESIGN A

1902
01:07:18,800 --> 01:07:20,600
SYSTEM THAT COULD BE ACCESSED

1903
01:07:20,600 --> 01:07:23,520
REMOTELY AND IT WAS PRETTY MUCH

1904
01:07:23,520 --> 01:07:26,160
SELF-SUFFICIENT, OTHER THAN THE

1905
01:07:26,160 --> 01:07:27,800
HUSBANDRY WITH THE ANIMALS.

1906
01:07:27,800 --> 01:07:30,880
SO THE PANDEMIC PRETTY MUCH

1907
01:07:30,880 --> 01:07:32,280
INSPIRED WHAT MY PROJECT IS NOW,

1908
01:07:32,280 --> 01:07:36,040
AND TO CREATE AN ENCLOSURE WHERE

1909
01:07:36,040 --> 01:07:37,200
WE COULD HAVE THE ANIMALS FOR

1910
01:07:37,200 --> 01:07:40,360
LONG PERIODS OF TIME, THAT WAS

1911
01:07:40,360 --> 01:07:41,240
INEXPENSIVE TO MATE THAT COULD

1912
01:07:41,240 --> 01:07:45,040
BE ACCESSED REMOTELY BECAUSE --

1913
01:07:45,040 --> 01:07:46,840
YOU CAN BE IN YOUR PJs AT HOME

1914
01:07:46,840 --> 01:07:48,240
AND LOOKING THROUGH THE CAMERAS

1915
01:07:48,240 --> 01:07:50,320
AND SEE IF YOUR ANIMALS ARE

1916
01:07:50,320 --> 01:07:51,400
DOING WELL AND THE ANALYSIS CAN

1917
01:07:51,400 --> 01:07:55,840
BE RUN REMOTELY.

1918
01:07:55,840 --> 01:07:56,960
>> I CAN ADD TO THAT.

1919
01:07:56,960 --> 01:07:58,840
I DO IMPLANTS WHICH IS ITSELF

1920
01:07:58,840 --> 01:08:01,440
VERY HARD TO GET, AND THEN WITH

1921
01:08:01,440 --> 01:08:03,040
COVID, I THINK WE HAD LIKE 1 1/2

1922
01:08:03,040 --> 01:08:09,280
YEARS WITH NO -- BECAUSE IN THE

1923
01:08:09,280 --> 01:08:10,920
HOSPITAL IT'S SUPER CHAOTIC SO

1924
01:08:10,920 --> 01:08:11,920
NO ONE WANTS TO DO THAT.

1925
01:08:11,920 --> 01:08:13,240
SO I THINK ONE THING THAT HELPED

1926
01:08:13,240 --> 01:08:16,120
ME TO MOVE FORWARD WAS TO DIG

1927
01:08:16,120 --> 01:08:18,760
MORE INTO THE LITERATURE.

1928
01:08:18,760 --> 01:08:19,920
MAINLY WHEN SOMEONE IS WORKING

1929
01:08:19,920 --> 01:08:21,360
IN DISCIPLINARY SCIENCES, I

1930
01:08:21,360 --> 01:08:24,000
THINK IT'S NEVER ENOUGH TO

1931
01:08:24,000 --> 01:08:25,400
LIKE -- NEVER ENOUGH NO MATTER

1932
01:08:25,400 --> 01:08:26,800
HOW MUCH YOU KNOW THE -- YOU'RE

1933
01:08:26,800 --> 01:08:27,160
WORKING ON.

1934
01:08:27,160 --> 01:08:30,320
SO I THINK I TAKE A LOT INTO

1935
01:08:30,320 --> 01:08:31,960
THAT AND EVEN STARTED WRITING

1936
01:08:31,960 --> 01:08:35,800
PAPERS BEFORE WE HAVE DATA JUST

1937
01:08:35,800 --> 01:08:36,760
LIKE THE INTRODUCTION AND STUFF

1938
01:08:36,760 --> 01:08:38,280
SO YOU CAN GET A HEAD START AND

1939
01:08:38,280 --> 01:08:39,480
NOW WHEN THINGS ARE BACK

1940
01:08:39,480 --> 01:08:42,760
RUNNING, I THINK THEY ARE GOING

1941
01:08:42,760 --> 01:08:43,240
PRETTY FAST.

1942
01:08:43,240 --> 01:08:44,520
SO THAT HELPED ME AT LEAST

1943
01:08:44,520 --> 01:08:51,000
PERSONALLY A LOT.

1944
01:08:51,000 --> 01:08:52,160
>> OKAY.

1945
01:08:52,160 --> 01:08:54,040
WE CAN COME BACK TO THAT AT ANY

1946
01:08:54,040 --> 01:08:55,240
POINT IF SOMEBODY HAS ANYTHING

1947
01:08:55,240 --> 01:08:56,320
REALLY INSIGHTFUL THEY WANT TO

1948
01:08:56,320 --> 01:08:57,000
SHARE.

1949
01:08:57,000 --> 01:08:58,200
LET'S SEE.

1950
01:08:58,200 --> 01:08:59,400
LUISA, YOU SPOKE A MOMENT AGO

1951
01:08:59,400 --> 01:09:01,120
BUT I'M GOING TO PUT YOU BACK IN

1952
01:09:01,120 --> 01:09:01,920
THE SPOTLIGHT AGAIN HERE.

1953
01:09:01,920 --> 01:09:02,920
THERE WAS A QUESTION THAT CAME

1954
01:09:02,920 --> 01:09:04,320
IN FOR YOU, AND IT SAID, HAVE

1955
01:09:04,320 --> 01:09:05,960
YOU LOOKED AT ANY OF YOUR

1956
01:09:05,960 --> 01:09:08,360
COLLECTED DATA USING OPEN SOURCE

1957
01:09:08,360 --> 01:09:09,880
TOOLS, TOOLS LIKE DEEP LAB CUT

1958
01:09:09,880 --> 01:09:12,640
OR TO USE OTHER SYSTEMS FOR YOUR

1959
01:09:12,640 --> 01:09:14,080
VIDEO ANALYSIS PIPELINE?

1960
01:09:14,080 --> 01:09:17,000
>> THAT'S A GOOD QUESTION.

1961
01:09:17,000 --> 01:09:18,560
SO THE IDEA OF MY PROJECT IS TO

1962
01:09:18,560 --> 01:09:22,520
MAKE IT AS LOW COST AS POSSIBLE.

1963
01:09:22,520 --> 01:09:26,960
SO I'VE BEEN USING -- TO TRACK

1964
01:09:26,960 --> 01:09:28,720
THE -- OF THE MOM WHEN SHE'S OUT

1965
01:09:28,720 --> 01:09:30,800
OF THE NEST BECAUSE THAT WAY, WE

1966
01:09:30,800 --> 01:09:32,400
CAN SYNCHRONIZE IT WITH LIKE OUR

1967
01:09:32,400 --> 01:09:34,080
THERMAL CAMERA AND LOOK AT THE

1968
01:09:34,080 --> 01:09:34,720
TEMPERATURE OF THE PUPS.

1969
01:09:34,720 --> 01:09:37,240
WE HAVE ALSO ANOTHER NETWORK

1970
01:09:37,240 --> 01:09:38,680
TRAINED TO IDENTIFY WHEN THE

1971
01:09:38,680 --> 01:09:40,640
PUPS ARE OUT OF THE NEST, AND WE

1972
01:09:40,640 --> 01:09:43,400
HAVE ANOTHER ONE TO IDENTIFY

1973
01:09:43,400 --> 01:09:46,080
ANIMALS OF THE SAME SIZE.

1974
01:09:46,080 --> 01:09:50,600
AND ALSO USING THAT -- DATA

1975
01:09:50,600 --> 01:09:53,440
WE'RE GETTING FROM DEEP LAB CUT,

1976
01:09:53,440 --> 01:09:54,960
MORE RECENTLY I'VE BEEN USING

1977
01:09:54,960 --> 01:09:56,800
OPEN SOURCE BEHAVIORAL

1978
01:09:56,800 --> 01:10:00,960
CLUSTERING SOFTWARE DEVELOPED

1979
01:10:00,960 --> 01:10:03,720
BY -- BECAUSE EVENTUALLY WE WANT

1980
01:10:03,720 --> 01:10:09,000
TO AUTOMATE AS MANY BEHAVIORS AS

1981
01:10:09,000 --> 01:10:10,280
POSSIBLE BECAUSE OUR VIDEOS ARE

1982
01:10:10,280 --> 01:10:11,920
SO LONG THAT DOING IT MANUALLY

1983
01:10:11,920 --> 01:10:16,080
IS IMPOSSIBLE.

1984
01:10:16,080 --> 01:10:17,600
SO EVERYTHING IN OUR ANALYSIS

1985
01:10:17,600 --> 01:10:19,480
PIPELINE IS OPEN SOURCE AND IT'S

1986
01:10:19,480 --> 01:10:20,440
BASED ON OTHER PEOPLE'S WORK.

1987
01:10:20,440 --> 01:10:22,680
SO I APPRECIATE THAT QUESTION.

1988
01:10:22,680 --> 01:10:26,240
THANK YOU.

1989
01:10:26,240 --> 01:10:28,320
>> THANK YOU, LUISA.

1990
01:10:28,320 --> 01:10:32,920
SO OUR NEXT QUESTION IS FOR WUI

1991
01:10:32,920 --> 01:10:33,240
JENG.

1992
01:10:33,240 --> 01:10:35,640
THE QUESTION IS, DO THESE MEAs

1993
01:10:35,640 --> 01:10:42,400
RESULT IN LESS GLIA ACTIVATION,

1994
01:10:42,400 --> 01:10:43,840
SCARRING --/SCARRING, THAN MORE

1995
01:10:43,840 --> 01:10:45,360
TRADITIONAL ELECTRODES?

1996
01:10:45,360 --> 01:10:46,840
>> FIRST THANKS FOR THE

1997
01:10:46,840 --> 01:10:49,000
QUESTION.

1998
01:10:49,000 --> 01:10:50,440
SO THIS PARTICULAR ARRAY, WE

1999
01:10:50,440 --> 01:10:53,480
HAVEN'T DONE ANY LINEAR RESPONSE

2000
01:10:53,480 --> 01:10:56,000
STAINING YET, SO THE ONLY

2001
01:10:56,000 --> 01:10:58,120
HISTOLOGY WORK I DID ON THIS

2002
01:10:58,120 --> 01:11:02,000
PROBE IS A NASAL STAIN SO I DO

2003
01:11:02,000 --> 01:11:05,760
SEE VERY LAST SCAR OR LIKE

2004
01:11:05,760 --> 01:11:06,760
WHATEVER -- AROUND THOSE PROBES.

2005
01:11:06,760 --> 01:11:09,000
BUT WE DO HAVE EXPERIENCE WITH

2006
01:11:09,000 --> 01:11:11,200
ANOTHER MICRO ELECTRODES ARRAY

2007
01:11:11,200 --> 01:11:15,480
WITH THE SAME MATERIAL WITH VERY

2008
01:11:15,480 --> 01:11:16,360
SIMILAR -- FROM OUR PREVIOUS

2009
01:11:16,360 --> 01:11:16,800
WORK.

2010
01:11:16,800 --> 01:11:19,200
FROM THAT ONE, WE DO SEE LESS

2011
01:11:19,200 --> 01:11:20,840
ACTIVATION OF SCAR TISSUE AND

2012
01:11:20,840 --> 01:11:24,000
SCARRING AROUND THE PROBE.

2013
01:11:24,000 --> 01:11:29,120
IT'S NOT A, LIKE, DRAMATIC --

2014
01:11:29,120 --> 01:11:30,240
DRAMATIC-REDUCING BUT SLIGHTLY

2015
01:11:30,240 --> 01:11:34,720
LESS AND COMPARABLE TO LIKE

2016
01:11:34,720 --> 01:11:36,720
MICRO WIRES AND MUCH BETTER

2017
01:11:36,720 --> 01:11:43,280
THAN -- PROBES.

2018
01:11:43,280 --> 01:11:50,000
>> THANKS FOR THAT.

2019
01:11:50,000 --> 01:11:50,920
BENJAMIN HAS A COUPLE OF

2020
01:11:50,920 --> 01:11:51,440
QUESTIONS HERE.

2021
01:11:51,440 --> 01:11:57,440
THERE'S A BIT OF PA   A PRIMACY

2022
01:11:57,440 --> 01:12:02,280
EFFECT HERE OR REESE SEE      -E

2023
01:12:02,280 --> 01:12:03,920
INTENSIVE IS RUNNING THIS

2024
01:12:03,920 --> 01:12:04,680
CONNECTOME CONNECTION

2025
01:12:04,680 --> 01:12:06,120
COMPARISON, AND CAN IT BE RUN ON

2026
01:12:06,120 --> 01:12:10,720
A DESKTOP OR IS GP PROCESSING

2027
01:12:10,720 --> 01:12:11,720
NEEDED?

2028
01:12:11,720 --> 01:12:13,000
>> SO THANKS FOR THE
QUESTION.

2029
01:12:13,000 --> 01:12:15,560
I GUESS THE SHORT ANSWER IS

2030
01:12:15,560 --> 01:12:16,720
EVERYTHING I'VE BEEN DOING, I

2031
01:12:16,720 --> 01:12:19,120
JUST RUN ON MY LAPTOP, SO IT'S

2032
01:12:19,120 --> 01:12:21,080
NOTHING WE'VE DONE SO FAR IS

2033
01:12:21,080 --> 01:12:24,240
VERY COMPUTATIONALLY EXPENSIVE.

2034
01:12:24,240 --> 01:12:26,120
IT TAKES -- MANY OF THESE TESTS

2035
01:12:26,120 --> 01:12:27,240
TAKE LESS THAN A SECOND.

2036
01:12:27,240 --> 01:12:28,080
SOME OF THE STUFF WE'RE WORKING

2037
01:12:28,080 --> 01:12:29,640
ON NOW, I THINK MIGHT END UP

2038
01:12:29,640 --> 01:12:31,800
BEING A BIT MORE COMPUTATIONALLY

2039
01:12:31,800 --> 01:12:34,000
EXPENSIVE, AND ALSO AS DATASET

2040
01:12:34,000 --> 01:12:35,120
GET LARGER, THAT MIGHT BE A

2041
01:12:35,120 --> 01:12:37,520
LITTLE BIT MORE OF A CONCERN,

2042
01:12:37,520 --> 01:12:40,320
BUT I DON'T THINK IT WOULD BE

2043
01:12:40,320 --> 01:12:41,640
PROHIBITIVE FOR RUNNING ANY OF

2044
01:12:41,640 --> 01:12:44,320
THESE COMPARISONS.

2045
01:12:44,320 --> 01:12:45,040
>> THANKS FOR THAT.

2046
01:12:45,040 --> 01:12:46,680
I WANTED TO ACTUALLY LOOK TO THE

2047
01:12:46,680 --> 01:12:49,400
PANELISTS AS WELL.

2048
01:12:49,400 --> 01:12:50,320
I SEE -- YOU'VE GOT YOUR HAND

2049
01:12:50,320 --> 01:12:50,600
UP.

2050
01:12:50,600 --> 01:12:51,480
IS THERE SOMETHING YOU WANT TO

2051
01:12:51,480 --> 01:12:52,240
JUMP IN ON HERE?

2052
01:12:52,240 --> 01:12:55,640
>> YEAH, I CAN HAVE A
QUESTION

2053
01:12:55,640 --> 01:12:58,200
FOR BENJAMIN AS WELL.

2054
01:12:58,200 --> 01:12:59,040
IT A MORE BASIC ONE.

2055
01:12:59,040 --> 01:13:00,440
I THINK YOU MENTIONED IN YOUR

2056
01:13:00,440 --> 01:13:01,560
PRESENTATION THAT ONE OF THE

2057
01:13:01,560 --> 01:13:03,280
PURPOSE TO LOOK AT THIS IS TO

2058
01:13:03,280 --> 01:13:06,600
STUDY BETWEEN SPECIES, HOW THE

2059
01:13:06,600 --> 01:13:08,240
CONNECTOMES ARE SIMILAR.

2060
01:13:08,240 --> 01:13:09,240
I'M JUST CURIOUS WHAT DO YOU

2061
01:13:09,240 --> 01:13:13,120
THINK CAN BE THE OOS FULL USEFUS

2062
01:13:13,120 --> 01:13:15,240
OF THAT, AND IF IT'S STRUCTURAL

2063
01:13:15,240 --> 01:13:15,960
OR FUNCTIONAL OR BOTH?

2064
01:13:15,960 --> 01:13:17,120
>> SO EVERYTHING THAT
WE'VE BEEN

2065
01:13:17,120 --> 01:13:20,160
DOING IS LOOKING AT STRUCTURAL

2066
01:13:20,160 --> 01:13:22,560
CONNECTOMES, BUT ONE OF OUR

2067
01:13:22,560 --> 01:13:25,400
COLLABORATORS IS VERY INTERESTED

2068
01:13:25,400 --> 01:13:28,160
IN, SAY, LOOKING AT A STRUCTURE

2069
01:13:28,160 --> 01:13:32,520
LIKE THE EYE AND HOW IT HAS

2070
01:13:32,520 --> 01:13:33,840
EVOLVED MULTIPLE TIMES OVER

2071
01:13:33,840 --> 01:13:35,320
EVOLUTION, SO IF YOU COULD LOOK

2072
01:13:35,320 --> 01:13:37,320
AT A CONNECTOME SAY OF A RETINA

2073
01:13:37,320 --> 01:13:39,720
FROM A SQUID AND THEN, YOU KNOW,

2074
01:13:39,720 --> 01:13:42,560
SOME MORE MAMMALIAN SPECIES AND

2075
01:13:42,560 --> 01:13:45,880
COMPARE, YOU MIGHT BE ABLE TO

2076
01:13:45,880 --> 01:13:48,360
FIND SOME COMMONALITIES OF THE

2077
01:13:48,360 --> 01:13:50,440
CIRCUIT THAT I GUESS TELL YOU

2078
01:13:50,440 --> 01:13:51,880
SOME GOOD THINGS ABOUT THAT

2079
01:13:51,880 --> 01:13:54,800
DESIGN THAT POP UP EVEN WHEN

2080
01:13:54,800 --> 01:13:57,800
THIS HAS EVOLVED INDEPENDENTLY.

2081
01:13:57,800 --> 01:13:59,200
YEAH, I'M NOT SURE IF -- DOES

2082
01:13:59,200 --> 01:14:07,640
THAT ANSWER YOUR QUESTION?

2083
01:14:07,640 --> 01:14:08,280
>> OKAY.

2084
01:14:08,280 --> 01:14:11,760
SO I ACTUALLY WANT TO RETURN TO

2085
01:14:11,760 --> 01:14:14,880
A QUESTION FOR MOHAMMAD

2086
01:14:14,880 --> 01:14:15,280
ACTUALLY.

2087
01:14:15,280 --> 01:14:16,600
I JUST FAILED TO WRITE THIS DOWN

2088
01:14:16,600 --> 01:14:19,320
MYSELF, BUT I WONDERED IF -- CAN

2089
01:14:19,320 --> 01:14:21,080
YOU TELL ME WHAT YOUR SOURCE

2090
01:14:21,080 --> 01:14:22,080
DATA IS FOR THAT?

2091
01:14:22,080 --> 01:14:25,000
IS IT SOMETHING YOU GENERATED IN

2092
01:14:25,000 --> 01:14:26,560
THE LAB SPECIFICALLY OR ARE YOU

2093
01:14:26,560 --> 01:14:27,760
USING OTHER DATA?

2094
01:14:27,760 --> 01:14:29,360
THERE'S SO MANY REALLY GOOD

2095
01:14:29,360 --> 01:14:30,720
DATASETS OUT THERE RIGHT NOW.

2096
01:14:30,720 --> 01:14:32,800
OF COURSE MANY OF THEM HAVE NOT

2097
01:14:32,800 --> 01:14:36,200
HAD PERTURBATIONS THE WAY YOU

2098
01:14:36,200 --> 01:14:37,840
USE BUT I WONDER WHAT THE NEXT

2099
01:14:37,840 --> 01:14:39,360
STEP FOR SOME OF THOSE STUDIES

2100
01:14:39,360 --> 01:14:41,080
MIGHT BE AND IF YOU CAN USE SOME

2101
01:14:41,080 --> 01:14:42,640
OF THE AVAILABLE DATA GENERATED

2102
01:14:42,640 --> 01:14:44,400
BY OTHERS.

2103
01:14:44,400 --> 01:14:45,680
>> THANK YOU SO MUCH.

2104
01:14:45,680 --> 01:14:52,120
THAT'S A GREAT QUESTION.

2105
01:14:52,120 --> 01:14:54,440
SO THE DATA, THE ANIMAL

2106
01:14:54,440 --> 01:14:55,880
EXPERIENCE, THESE ARE IN VIVO,

2107
01:14:55,880 --> 01:14:58,320
THE LTP INDUCTION IS DONE IN

2108
01:14:58,320 --> 01:15:06,040
VIVO IN ADULT RAT AND THEN AFTER

2109
01:15:06,040 --> 01:15:10,720
THE INDUCTION -- ANIMAL, THEY

2110
01:15:10,720 --> 01:15:13,480
ARE TRANSPORTED TO PROFESSOR

2111
01:15:13,480 --> 01:15:16,960
KRISTEN -- LAB AT -- AUSTIN FOR

2112
01:15:16,960 --> 01:15:18,600
MICROSCOPY AND THEN THE

2113
01:15:18,600 --> 01:15:19,360
ELECTROMICROGRAPHS WERE TAKEN,

2114
01:15:19,360 --> 01:15:22,240
AND THEN THEY WERE TRANSFERRED

2115
01:15:22,240 --> 01:15:25,480
AFTER THAT TO THE LAB FOR THREE

2116
01:15:25,480 --> 01:15:29,200
DIMENSIONAL SERIAL SECTION

2117
01:15:29,200 --> 01:15:31,640
ELECTROMICROSCOPY SO 3D

2118
01:15:31,640 --> 01:15:34,160
RECONSTRUCTION IS DONE IN THE

2119
01:15:34,160 --> 01:15:36,960
SIDOSKY LAB, SO AFTER THAT, THE

2120
01:15:36,960 --> 01:15:37,600
COMPUTATIONAL ANALYSIS HAS BEEN

2121
01:15:37,600 --> 01:15:38,600
DONE AND IT IS VERY IMPORTANT,

2122
01:15:38,600 --> 01:15:42,120
THANK YOU FOR POINTING --

2123
01:15:42,120 --> 01:15:43,120
REGARDING YOUR NEXT STEPS, SO

2124
01:15:43,120 --> 01:15:50,080
THE REALITY OF THESE COULD NECKT

2125
01:15:50,080 --> 01:15:51,840
OMIC DATA AND OTHER COLLEAGUES

2126
01:15:51,840 --> 01:15:53,280
IN THE GROUP IN THE PANEL HAS

2127
01:15:53,280 --> 01:15:56,680
TALKED ABOUT IT IS THAT THEY ARE

2128
01:15:56,680 --> 01:15:57,920
RARE AND THEY ARE DONE

2129
01:15:57,920 --> 01:15:58,360
DIFFERENTLY.

2130
01:15:58,360 --> 01:16:00,720
FOR EXAMPLE, IN OUR DATA, WHICH

2131
01:16:00,720 --> 01:16:03,240
IS THE LONG TERM POTENTIATION

2132
01:16:03,240 --> 01:16:08,600
INDUCTION OF -- TWO HOUR, THE

2133
01:16:08,600 --> 01:16:11,000
THREE HOUR, FOUR HOUR OR ONE DAY

2134
01:16:11,000 --> 01:16:11,800
DOES NOT EXIST.

2135
01:16:11,800 --> 01:16:13,840
SO THAT'S IT, THAT'S THE DATA,

2136
01:16:13,840 --> 01:16:18,000
VERY RARE DATA, THIS IS ONE

2137
01:16:18,000 --> 01:16:18,280
LIMITATION.

2138
01:16:18,280 --> 01:16:19,840
THE OTHER LIMITATION, MOST OF

2139
01:16:19,840 --> 01:16:22,240
THE DATA THAT ARE EXISTING OUT

2140
01:16:22,240 --> 01:16:24,480
THERE THAT YOU POINTED, THERE

2141
01:16:24,480 --> 01:16:28,400
ARE NOT A LOT, THERE ARE A FEW

2142
01:16:28,400 --> 01:16:29,840
CONNECT OMICS DATA, BUT THEY'RE

2143
01:16:29,840 --> 01:16:31,440
IN A SINGLE ANIMAL.

2144
01:16:31,440 --> 01:16:33,960
SO IF ANYTHING SPECIAL, ANY BIAS

2145
01:16:33,960 --> 01:16:35,360
ON THAT ARE THE OR MICE, OKAY,

2146
01:16:35,360 --> 01:16:36,040
YOU ARE DONE.

2147
01:16:36,040 --> 01:16:38,880
SO THEY CLAIM THEY HAVE, FOR

2148
01:16:38,880 --> 01:16:39,760
EXAMPLE, 300 MILLION SYNAPSES,

2149
01:16:39,760 --> 01:16:41,640
WHICH IS GREAT, BUT THIS IS FOR

2150
01:16:41,640 --> 01:16:46,080
A SINGLE ANIMAL, MICE, RAT OR

2151
01:16:46,080 --> 01:16:46,800
DROSOPHILA, SO THIS IS THE

2152
01:16:46,800 --> 01:16:47,080
LIMITATION.

2153
01:16:47,080 --> 01:16:49,960
I MEAN, WE ARE LUCKY HERE TO

2154
01:16:49,960 --> 01:16:50,480
HAVE FIVE RATS.

2155
01:16:50,480 --> 01:16:52,040
IT'S NOT A HUGE N, BUT THE

2156
01:16:52,040 --> 01:16:54,960
NUMBER OF ANIMALS WERE FIVE.

2157
01:16:54,960 --> 01:16:59,360
WE HAD CONTROL, WE HAD LTP30 --

2158
01:16:59,360 --> 01:17:00,760
TWO HOURS, SO IT WAS A GREAT

2159
01:17:00,760 --> 01:17:03,480
OPPORTUNITY TO INVESTIGATE

2160
01:17:03,480 --> 01:17:07,520
DIFFERENT ASPECT OF THE

2161
01:17:07,520 --> 01:17:10,080
PRECISIONAL SYNAPTIC -- SYNAPTIC

2162
01:17:10,080 --> 01:17:10,800
INFORMATION, STORAGE CAPACITY

2163
01:17:10,800 --> 01:17:13,920
AND MANY OTHER ANALYSIS WE HAVE

2164
01:17:13,920 --> 01:17:14,200
DONE.

2165
01:17:14,200 --> 01:17:17,280
SO I JUST WANTED TO POINT THIS

2166
01:17:17,280 --> 01:17:20,600
OUT THAT WE HAVE A VERY LIMITED

2167
01:17:20,600 --> 01:17:24,600
DATASET IN COULD NECK TOE MIBG

2168
01:17:24,600 --> 01:17:26,360
COMMUNITY TO EXPLORE -- TO

2169
01:17:26,360 --> 01:17:28,320
HAVE -- I MEAN, IN OUR FREEDOM

2170
01:17:28,320 --> 01:17:29,320
TO EXPLORE DIFFERENT

2171
01:17:29,320 --> 01:17:30,720
COMPUTATIONAL METHODS.

2172
01:17:30,720 --> 01:17:34,200
YOU NEED TO HAVE A HIGH END TO

2173
01:17:34,200 --> 01:17:35,440
DO INFOR INSTANCE ANALYSIS, YOU

2174
01:17:35,440 --> 01:17:37,720
NEED TO HAVE DIFFERENT

2175
01:17:37,720 --> 01:17:39,720
CONDITIONS TO FIND CORRELATION

2176
01:17:39,720 --> 01:17:41,680
TO FIND CAUSATION, AND WE ARE

2177
01:17:41,680 --> 01:17:44,040
VERY LIMITED TO THE DATA, TO THE

2178
01:17:44,040 --> 01:17:44,520
QUALITY.

2179
01:17:44,520 --> 01:17:46,480
I AS A COMPUTATIONAL PERSON HAD

2180
01:17:46,480 --> 01:17:49,320
THE FOREFRONT OF THE PROJECT

2181
01:17:49,320 --> 01:17:52,960
NEEDS MANY DIFFERENT CHANGES BUT

2182
01:17:52,960 --> 01:17:54,360
THERE IS NO WAY TO DO THOSE

2183
01:17:54,360 --> 01:17:55,560
CHANGES BECAUSE WE SHOULD GO

2184
01:17:55,560 --> 01:17:58,640
BACK AND DO THE EXPERIMENT.

2185
01:17:58,640 --> 01:18:00,680
SO THEY FIRST DO THE EXPERIMENT

2186
01:18:00,680 --> 01:18:04,200
AND THEN AT THE LAST STAGE, THE

2187
01:18:04,200 --> 01:18:05,400
COMPUTATIONAL PERSON STARTS

2188
01:18:05,400 --> 01:18:06,920
ANALYZING AND ANALYZING LATER

2189
01:18:06,920 --> 01:18:08,480
AND YOU NEED MANY THINGS BUT YOU

2190
01:18:08,480 --> 01:18:10,080
CAN GO BACK AND DO ANOTHER

2191
01:18:10,080 --> 01:18:11,080
ANIMAL, BUT REGARDING THE OTHER

2192
01:18:11,080 --> 01:18:12,840
QUESTIONS YOU HAD, THESE ARE

2193
01:18:12,840 --> 01:18:16,640
HAND TRACED, SO THE DATA WE

2194
01:18:16,640 --> 01:18:18,640
HAVE, THE ACTUAL MICROGRAPHS

2195
01:18:18,640 --> 01:18:23,880
THAT ARE PROVIDED AT AUSTIN,

2196
01:18:23,880 --> 01:18:25,000
THEY WERE MAYBE TWO YEARS OF

2197
01:18:25,000 --> 01:18:26,800
HAND TRACING TO HAVE THESE

2198
01:18:26,800 --> 01:18:28,800
MICROGRAPHS READY FOR 3D

2199
01:18:28,800 --> 01:18:29,200
RECONSTRUCTION.

2200
01:18:29,200 --> 01:18:30,760
SO I HOPE I ADDRESSED ALL THE

2201
01:18:30,760 --> 01:18:31,480
QUESTIONS YOU POINTED.

2202
01:18:31,480 --> 01:18:33,520
>> YEAH, THANK YOU.

2203
01:18:33,520 --> 01:18:35,600
THOSE CLARIFICATIONS ARE REALLY

2204
01:18:35,600 --> 01:18:36,320
A VERY SIGNIFICANT POINT.

2205
01:18:36,320 --> 01:18:37,480
THANK YOU.

2206
01:18:37,480 --> 01:18:40,720
>> THANK YOU.

2207
01:18:40,720 --> 01:18:42,480
>> BENJAMIN, YOU HAVE A
HAND UP.

2208
01:18:42,480 --> 01:18:45,120
WOULD YOU LIKE TO JUMP IN?

2209
01:18:45,120 --> 01:18:48,160
>> I REALLY WOULD LIKE TO
JUST

2210
01:18:48,160 --> 01:18:50,120
ECHO WHAT MOHAMMAD WAS SAYING

2211
01:18:50,120 --> 01:18:51,600
ABOUT THE INCREASING NEED IN

2212
01:18:51,600 --> 01:18:54,280
COULD NECK TOE MIBGS TO HAVE

2213
01:18:54,280 --> 01:18:55,480
MULTIPLE SAMPLES WHERE YOU CAN

2214
01:18:55,480 --> 01:18:56,600
START TO DO PER TEU BAIGS AS

2215
01:18:56,600 --> 01:19:00,040
WELL            PERTURBATIONS AS

2216
01:19:00,040 --> 01:19:02,040
WELL AS SORT OF HAVING AN IDEA

2217
01:19:02,040 --> 01:19:04,680
OF WHAT WE'RE LOOKING FOR BEFORE

2218
01:19:04,680 --> 01:19:06,840
WE CONNECT THE CONNECTOME AND

2219
01:19:06,840 --> 01:19:08,960
SORT OF WHAT ANALYSIS ONE COULD

2220
01:19:08,960 --> 01:19:12,080
DO TO GET OUT THESE QUESTIONS

2221
01:19:12,080 --> 01:19:13,440
THAT WE'RE INTERESTED IN, JUST

2222
01:19:13,440 --> 01:19:14,400
SOMETHING THAT'S COME UP FOR ME

2223
01:19:14,400 --> 01:19:15,440
AS WELL IN MY WORK, SO I JUST

2224
01:19:15,440 --> 01:19:19,440
ANY TIME WAKED TO ECHO        W.

2225
01:19:19,440 --> 01:19:20,960
>> LET ME BUILD ON THAT
SLIGHTLY

2226
01:19:20,960 --> 01:19:23,280
AND MAYBE TAKE A BIT OF A PIVOT.

2227
01:19:23,280 --> 01:19:24,800
THE NIH HAS BEEN INVESTING IN

2228
01:19:24,800 --> 01:19:26,200
SORT OF THIS CONNECTOME SPACE

2229
01:19:26,200 --> 01:19:27,840
FOR A WHILE.

2230
01:19:27,840 --> 01:19:29,840
IT HAS GROWN CONSIDERABLY AND IT

2231
01:19:29,840 --> 01:19:32,880
HAS CHANGED IN CIRCUIT -- CROSS

2232
01:19:32,880 --> 01:19:35,840
LEVELS AS WELL.

2233
01:19:35,840 --> 01:19:37,160
AND THERE HAS BEEN A BIG PUSH

2234
01:19:37,160 --> 01:19:39,680
AND SO MOHAMMAD SORT OF TOUCHED

2235
01:19:39,680 --> 01:19:41,520
ON THIS, THE IDEA OF SLAIRED

2236
01:19:41,520 --> 01:19:42,240
DATASETS.

2237
01:19:42,240 --> 01:19:46,880
HOW VALUABLE ARE THEY, WHAT'S

2238
01:19:46,880 --> 01:19:48,880
THE VARIABILITY BETWEEN THEM,

2239
01:19:48,880 --> 01:19:49,640
WHAT'S CONSISTENT BETWEEN THEM

2240
01:19:49,640 --> 01:19:52,280
SO YOU CAN ACTUALLY POOL THINGS.

2241
01:19:52,280 --> 01:19:53,800
THAT'S BEEN A MASSIVE PUSH.

2242
01:19:53,800 --> 01:19:55,200
WE'VE HEARD A LOT OF CIRCUIT

2243
01:19:55,200 --> 01:19:56,800
STUFF BUT THIS GOES DOWN TO THE

2244
01:19:56,800 --> 01:19:57,960
CELLULAR LEVEL AS WELL.

2245
01:19:57,960 --> 01:19:59,520
CERTAINLY AT LEAST MOHAMMAD

2246
01:19:59,520 --> 01:20:01,640
YOU'RE TALKING ABOUT CHRISTIAN

2247
01:20:01,640 --> 01:20:02,720
HARRIS' WORK, WE'RE TALKING

2248
01:20:02,720 --> 01:20:04,040
ABOUT EM LEVEL AS WELL.

2249
01:20:04,040 --> 01:20:05,040
SO THAT'S A CHALLENGE.

2250
01:20:05,040 --> 01:20:07,240
THAT'S ONE OF THESE EVOLVING

2251
01:20:07,240 --> 01:20:08,200
CHALLENGES, THE IDEA THAT THE

2252
01:20:08,200 --> 01:20:10,840
NIH IS PUSHING ON DATA SHARING

2253
01:20:10,840 --> 01:20:13,600
SO THAT YOU HAVE THESE RESOURCES

2254
01:20:13,600 --> 01:20:15,560
AVAILABLE TO MAXIMIZE THE

2255
01:20:15,560 --> 01:20:17,480
INVESTMENT THAT THE TAXICABS

2256
01:20:17,480 --> 01:20:23,520
PAIR HAS MADE TO              TS

2257
01:20:23,520 --> 01:20:24,280
MADE IN SCIENCE.

2258
01:20:24,280 --> 01:20:27,800
TO PIVOT SLIGHTLY, THOUGH, I'M

2259
01:20:27,800 --> 01:20:30,120
NOT GOING TO PUT YOU BY NAME ON

2260
01:20:30,120 --> 01:20:31,520
THE SPOT BUT I'M GOING TO ASK

2261
01:20:31,520 --> 01:20:32,920
THOSE PEOPLE WHO ARE MORE SENIOR

2262
01:20:32,920 --> 01:20:37,120
ON THE PAM,    PANEL, SENIOR, AE

2263
01:20:37,120 --> 01:20:37,560
TERM, RIGHT?

2264
01:20:37,560 --> 01:20:39,000
THOSE OF YOU THAT ARE POSTDOCS,

2265
01:20:39,000 --> 01:20:40,400
YOU'RE THE SENIOR PEOPLE ON THIS

2266
01:20:40,400 --> 01:20:40,800
PANEL, OKAY?

2267
01:20:40,800 --> 01:20:42,560
SO THOSE OF YOU THAT ARE

2268
01:20:42,560 --> 01:20:43,880
POSTDOC, I'M WONDERING IF YOU

2269
01:20:43,880 --> 01:20:47,160
COULD SHARE YOUR THOUGHTS AS TO

2270
01:20:47,160 --> 01:20:51,200
HOW YOU SELECTED YOUR POSTDOC

2271
01:20:51,200 --> 01:20:52,400
LAB, WHAT SOME OF THOSE

2272
01:20:52,400 --> 01:20:54,360
CHALLENGES HAVE BEEN AND WHAT

2273
01:20:54,360 --> 01:20:56,040
RECOMMENDATIONS YOU MIGHT GIVE

2274
01:20:56,040 --> 01:20:58,640
TO YOUR OTHER SELF IF YOU CAN GO

2275
01:20:58,640 --> 01:20:59,840
BACK IN TIME.

2276
01:20:59,840 --> 01:21:00,840
OBVIOUSLY YOU DON'T WANT TO SAY

2277
01:21:00,840 --> 01:21:02,040
ANYTHING THAT'S GOING TO PUT NEW

2278
01:21:02,040 --> 01:21:03,440
HOT WATER, BUT I KNOW FOR SOME

2279
01:21:03,440 --> 01:21:06,040
OF YOU, AT LEAST ONE OF YOU,

2280
01:21:06,040 --> 01:21:07,800
YOU'VE JUMPED INTO THAT LAB THAT

2281
01:21:07,800 --> 01:21:08,960
WAS BRAND NEW ESSENTIALLY, AND

2282
01:21:08,960 --> 01:21:10,040
THERE ARE UNIQUE CHALLENGES WITH

2283
01:21:10,040 --> 01:21:10,360
THAT.

2284
01:21:10,360 --> 01:21:11,240
SO IF YOU HAVE THOUGHTS ABOUT

2285
01:21:11,240 --> 01:21:12,560
THAT, I THINK THERE MAY BE

2286
01:21:12,560 --> 01:21:14,400
OTHERS THAT ARE LISTENING WHO

2287
01:21:14,400 --> 01:21:18,040
WOULD POTENTIALLY BENEFIT FROM

2288
01:21:18,040 --> 01:21:26,440
THAT.

2289
01:21:26,440 --> 01:21:27,520
EVERYBODY IS TRYING TO SAY

2290
01:21:27,520 --> 01:21:28,400
SOMETHING, YOU'RE ALL ON MUTE.

2291
01:21:28,400 --> 01:21:29,600
GO AHEAD AND UNMUTE.

2292
01:21:29,600 --> 01:21:33,960
>> SO I THINK I'M KIND OF
SENIOR

2293
01:21:33,960 --> 01:21:34,400
HERE.

2294
01:21:34,400 --> 01:21:35,920
SO I ACTUALLY STAYED IN MY OWN

2295
01:21:35,920 --> 01:21:36,280
LAB.

2296
01:21:36,280 --> 01:21:40,000
I DID MY PH.D. WITH -- AND

2297
01:21:40,000 --> 01:21:44,160
STAYED HERE BECAUSE -- GIVE US

2298
01:21:44,160 --> 01:21:47,760
THIS GREAT OPPORTUNITY TO --

2299
01:21:47,760 --> 01:21:50,160
WHICH ALLOWS US TO PROVIDE

2300
01:21:50,160 --> 01:21:52,360
SERVICE TO THE GREAT

2301
01:21:52,360 --> 01:21:53,040
NEUROSCIENCE COMMUNITY.

2302
01:21:53,040 --> 01:21:55,840
THE OTHER REASON I STATE HERE IS

2303
01:21:55,840 --> 01:21:59,800
DEFINITELY BECAUSE THIS PROJECT

2304
01:21:59,800 --> 01:22:01,760
THAT'S DEVELOPING POLYMER

2305
01:22:01,760 --> 01:22:03,800
DEVICES, FOR MYSELF I THINK ONE

2306
01:22:03,800 --> 01:22:05,480
BIGGEST CHALLENGE WITHIN THIS

2307
01:22:05,480 --> 01:22:06,360
NEUROSCIENCE AND

2308
01:22:06,360 --> 01:22:07,320
NEUROENGINEERING COMMUNITY IS

2309
01:22:07,320 --> 01:22:12,040
STILL HOW TO COLLECT VERY HIGH

2310
01:22:12,040 --> 01:22:12,800
QUALITY LONG TERM -- DATA.

2311
01:22:12,800 --> 01:22:14,120
I THINK THAT'S THE FOUNDATION TO

2312
01:22:14,120 --> 01:22:15,440
UNDERSTAND ALL THE FUNCTIONS OF

2313
01:22:15,440 --> 01:22:17,520
OUR BRAIN.

2314
01:22:17,520 --> 01:22:22,680
SO IF WE CAN DEVELOP TOURS TO TO

2315
01:22:22,680 --> 01:22:24,080
BETTER COLLECT -- TO DO THIS

2316
01:22:24,080 --> 01:22:25,320
FOUNDATION, I THINK IT'S VERY

2317
01:22:25,320 --> 01:22:25,840
MEANINGFUL.

2318
01:22:25,840 --> 01:22:30,040
SO MY EXPERIENCE DOESN'T -- I

2319
01:22:30,040 --> 01:22:33,080
KNOW IT'S LIKE NOT -- SOME

2320
01:22:33,080 --> 01:22:34,400
PEOPLE SAY IT'S NOT GOOD IF YOU

2321
01:22:34,400 --> 01:22:35,920
WANT TO STAY IN ACADEMIA, IT'S

2322
01:22:35,920 --> 01:22:37,240
NOT GOOD TO STAY IN THE SAME LAB

2323
01:22:37,240 --> 01:22:41,720
FOR VERY LONG.

2324
01:22:41,720 --> 01:22:44,240
BUT MINE IS A VERY SPECIAL CASE.

2325
01:22:44,240 --> 01:22:47,160
SO JUST WANT TO START TO -- SO

2326
01:22:47,160 --> 01:22:48,840
PEOPLE CAN JUMP IN.

2327
01:22:48,840 --> 01:22:51,440
>> SO LET ME PUSH ON THAT
A

2328
01:22:51,440 --> 01:22:52,320
LITTLE FURTHER.

2329
01:22:52,320 --> 01:22:54,280
IN FACT I THINK -- ROHIT, YOU

2330
01:22:54,280 --> 01:22:55,160
HAVE A QUESTION THAT SORT OF

2331
01:22:55,160 --> 01:22:57,800
BUILDS ON THAT AS FAR AS

2332
01:22:57,800 --> 01:22:58,800
ALIGNING -- NOT ALIGNING BUT

2333
01:22:58,800 --> 01:23:02,920
SORT OF THINKING ABOUT YOUR

2334
01:23:02,920 --> 01:23:04,400
RESEARCH DIRECTION AND HOW IT'S

2335
01:23:04,400 --> 01:23:06,440
GOING TO BE SUPPORTED IN THE

2336
01:23:06,440 --> 01:23:06,680
FUTURE.

2337
01:23:06,680 --> 01:23:07,880
DO YOU WANT TO ASK YOUR

2338
01:23:07,880 --> 01:23:08,120
QUESTION?

2339
01:23:08,120 --> 01:23:09,600
>> YES, SURELY.

2340
01:23:09,600 --> 01:23:14,400
SO MAYBE NOT -- THIRD YEAR

2341
01:23:14,400 --> 01:23:16,080
GRADUATE STUDENT, I'M SLOWLY

2342
01:23:16,080 --> 01:23:17,320
THINKING THERE'S QUESTIONS I

2343
01:23:17,320 --> 01:23:18,560
WANT TO ASK FURTHER PROBABLY

2344
01:23:18,560 --> 01:23:21,320
AFTER MY PH.D., BUT -- AND I

2345
01:23:21,320 --> 01:23:23,280
WANT TO DO A -- IN ACADEMIA.

2346
01:23:23,280 --> 01:23:25,000
AND THEN I'M THINK HOW SHOULD I

2347
01:23:25,000 --> 01:23:26,440
NARROW THIS DOWN IN TERMS OF

2348
01:23:26,440 --> 01:23:28,320
PRIORITY SO THAT I CAN ALSO GET

2349
01:23:28,320 --> 01:23:29,840
EASY FUNDING FROM THE FUNDING

2350
01:23:29,840 --> 01:23:30,440
AGENCIES.

2351
01:23:30,440 --> 01:23:33,800
LIKE HOWL TO DO       HOW TO DOO

2352
01:23:33,800 --> 01:23:36,200
START DOING THAT, WHEN TO START

2353
01:23:36,200 --> 01:23:37,840
APPLYING FOR GRANTS IS A

2354
01:23:37,840 --> 01:23:39,920
QUESTION OF THAT.

2355
01:23:39,920 --> 01:23:41,640
>> SO I SUPPOSE FROM A

2356
01:23:41,640 --> 01:23:43,480
MANAGEMENT PERSPECTIVE, I'M IN

2357
01:23:43,480 --> 01:23:44,080
PROBABLY THE BEST POSITION TO

2358
01:23:44,080 --> 01:23:45,040
ANSWER THE QUESTION, BUT I WANT

2359
01:23:45,040 --> 01:23:46,360
TO SEE IF ANYBODY ON THE PANEL

2360
01:23:46,360 --> 01:23:53,800
HAS ANY THOUGHTS FIRST.

2361
01:23:53,800 --> 01:23:57,600
>> OR IF YOU'VE GOTTEN ANY

2362
01:23:57,600 --> 01:23:59,240
ADVICE ALONG THE LINES FROM YOUR

2363
01:23:59,240 --> 01:24:00,880
MENTORS OR ADVISORS, OR IF YOU

2364
01:24:00,880 --> 01:24:02,120
WANT TO THINK ABOUT IT FOR A

2365
01:24:02,120 --> 01:24:03,400
SECOND, JAY CAN GIVE THE

2366
01:24:03,400 --> 01:24:04,400
MANAGEMENT EXPERIENCE THAT HE

2367
01:24:04,400 --> 01:24:04,560
HAS.

2368
01:24:04,560 --> 01:24:07,680
>> YEAH, SO LET ME SORT OF
MAYBE

2369
01:24:07,680 --> 01:24:08,760
BREAK THE ICE ON THAT.

2370
01:24:08,760 --> 01:24:10,520
ONE IS, ACTUALLY I WILL HAVE A

2371
01:24:10,520 --> 01:24:12,480
LITTLE BIT BECAUSE YOU SAID THE

2372
01:24:12,480 --> 01:24:14,080
EASY PATH TO FUNDING, WHAT IS

2373
01:24:14,080 --> 01:24:14,680
THAT?

2374
01:24:14,680 --> 01:24:15,760
THAT DOES NOT EXIST.

2375
01:24:15,760 --> 01:24:17,280
AND THE SOONER WE CAN ACCEPT

2376
01:24:17,280 --> 01:24:19,080
THAT, THAT THAT IS A REALITY,

2377
01:24:19,080 --> 01:24:21,240
THE BETTER OFF WE'LL BE.

2378
01:24:21,240 --> 01:24:22,680
UNFORTUNATELY THERE IS MORE

2379
01:24:22,680 --> 01:24:24,320
GREAT SCIENTIFIC QUESTIONS THAN

2380
01:24:24,320 --> 01:24:26,480
THERE ARE MONEY TO SUPPORT IT,

2381
01:24:26,480 --> 01:24:27,720
IS WHAT IT COMES DOWN TO.

2382
01:24:27,720 --> 01:24:28,920
SO HOW DO YOU MOVE FORWARD?

2383
01:24:28,920 --> 01:24:29,960
I THINK THERE'S A COUPLE OF

2384
01:24:29,960 --> 01:24:30,200
WAYS.

2385
01:24:30,200 --> 01:24:32,000
ONE IS THAT I THINK YOU FIRST OF

2386
01:24:32,000 --> 01:24:35,360
ALL FROM A HYPOTHETICAL

2387
01:24:35,360 --> 01:24:38,440
PERSPECTIVE, YOU WANT TO LOOK TO

2388
01:24:38,440 --> 01:24:40,280
SEE WHAT'S WORKED FOR OTHERS.

2389
01:24:40,280 --> 01:24:41,680
THIS IS CHALLENGING.

2390
01:24:41,680 --> 01:24:42,360
WE HAD INITIAL CONVERSATIONS

2391
01:24:42,360 --> 01:24:43,640
ABOUT HOW DOES SOMEBODY COME AT

2392
01:24:43,640 --> 01:24:45,440
THIS FROM AN ENGINEERING SPER

2393
01:24:45,440 --> 01:24:46,720
SPECULATIVE WHERE THE NIH IS A

2394
01:24:46,720 --> 01:24:47,840
BIT OF A FOREIGN ENTITY.

2395
01:24:47,840 --> 01:24:49,520
A LOT OF ENGINEERS, NOT ALL BUT

2396
01:24:49,520 --> 01:24:51,200
A LOT OF ENGINEERS, THIS IS NOT

2397
01:24:51,200 --> 01:24:52,080
THEIR NORMAL SORT OF WAY.

2398
01:24:52,080 --> 01:24:53,600
I WILL SAY THE BRAIN INITIATIVE

2399
01:24:53,600 --> 01:24:55,920
HAS REALLY PUSHED EXPANDING THE

2400
01:24:55,920 --> 01:24:57,320
DIVERSITY OF PERSPECTIVES WE

2401
01:24:57,320 --> 01:24:59,680
HAVE, AND THAT DIVERSITY SPANS A

2402
01:24:59,680 --> 01:25:01,280
LOT OF DIFFERENT DIMENSIONS.

2403
01:25:01,280 --> 01:25:05,120
ONE OF THOSE IS ACTUALLY CAREER

2404
01:25:05,120 --> 01:25:05,400
EXPERTISE.

2405
01:25:05,400 --> 01:25:06,760
SO WE WANT TO BRING IN PEOPLE

2406
01:25:06,760 --> 01:25:08,920
WHO ARE OUTSIDE OF OUR NORMAL

2407
01:25:08,920 --> 01:25:12,000
SHALL WE SAY CHOIR OF

2408
01:25:12,000 --> 01:25:12,440
INVESTIGATORS.

2409
01:25:12,440 --> 01:25:14,080
NOT JUST NEUROSCIENTISTS FOR THE

2410
01:25:14,080 --> 01:25:16,160
BRAIN INITIATIVE, BUT PEOPLE WHO

2411
01:25:16,160 --> 01:25:17,120
REALLY BRING A DIFFERENT

2412
01:25:17,120 --> 01:25:17,560
PERSPECTIVE.

2413
01:25:17,560 --> 01:25:19,640
SO WE VALUE -- I MEAN, I LOOK

2414
01:25:19,640 --> 01:25:20,880
AROUND THIS VIRTUAL ROOM IN

2415
01:25:20,880 --> 01:25:22,280
FRONT OF US.

2416
01:25:22,280 --> 01:25:23,880
WE VALUE THE DIFFERENT

2417
01:25:23,880 --> 01:25:25,320
PERSPECTIVES YOU HAVE.

2418
01:25:25,320 --> 01:25:26,880
SO IT IS HUGELY IMPORTANT THAT

2419
01:25:26,880 --> 01:25:27,960
WE FIND ANSWERS FOR THAT.

2420
01:25:27,960 --> 01:25:29,280
NOW THE MORE DIRECT ANSWER, I

2421
01:25:29,280 --> 01:25:30,480
WOULD SAY, IS THAT THERE ARE

2422
01:25:30,480 --> 01:25:33,440
FUNDING MECHANISMS AVAILABLE TO

2423
01:25:33,440 --> 01:25:34,960
ALL CAREER STAGES FOR A VARIETY

2424
01:25:34,960 --> 01:25:36,760
OF DIFFERENT REASONS.

2425
01:25:36,760 --> 01:25:38,160
NOW I'LL BE THE FIRST TO ADMIT,

2426
01:25:38,160 --> 01:25:39,880
YOU'RE GOING TO LOOK AT THESE

2427
01:25:39,880 --> 01:25:41,520
LETTERS, THESE Ks AND Fs AND

2428
01:25:41,520 --> 01:25:42,600
ALL OF THESE THINGS AND IT'S

2429
01:25:42,600 --> 01:25:44,560
GOING TO BE MUMBO JUMBO TO A LOT

2430
01:25:44,560 --> 01:25:47,440
OF YOU.

2431
01:25:47,440 --> 01:25:50,920
BOUTS   BECAUSE IT'S A FOREIGN .

2432
01:25:50,920 --> 01:25:52,680
BR THERE'S WHERE NIH PROGRAM

2433
01:25:52,680 --> 01:25:54,000
OFFICIALS ARE HERE TO HELP.

2434
01:25:54,000 --> 01:25:55,120
SO ANDREA AND I, THE TWO THAT

2435
01:25:55,120 --> 01:25:57,400
ARE ON THIS CALL RIGHT NOW, CAN

2436
01:25:57,400 --> 01:26:00,920
ABSOLUTELY HELP OUT.

2437
01:26:00,920 --> 01:26:02,400
IF IT'S NOT RELEVANT FOR MY

2438
01:26:02,400 --> 01:26:04,360
RESEARCH PROGRAM, I DON'T WANT

2439
01:26:04,360 --> 01:26:05,360
TO JUST SAY NO THANK YOU AND

2440
01:26:05,360 --> 01:26:06,000
PUSH YOU OFF.

2441
01:26:06,000 --> 01:26:08,880
WE WANT TO FIND THE RIGHT PLACE.

2442
01:26:08,880 --> 01:26:10,080
AND SOMETIMES THE RIGHT PLACE

2443
01:26:10,080 --> 01:26:12,040
ISN'T OH, WE HAVE A PROGRAM FOR

2444
01:26:12,040 --> 01:26:13,120
THAT.

2445
01:26:13,120 --> 01:26:14,120
SOMETIMES IT'S, SORRY, THAT'S

2446
01:26:14,120 --> 01:26:15,760
ACTUALLY NOT IN OUR LANE FOR

2447
01:26:15,760 --> 01:26:16,760
WHAT WE CAN DO.

2448
01:26:16,760 --> 01:26:18,200
HAVE YOU THOUGHT ABOUT THESE

2449
01:26:18,200 --> 01:26:22,440
OTHER PLACES AS WELL?

2450
01:26:22,440 --> 01:26:23,960
SO REALLY THE LONG WINDED SORT

2451
01:26:23,960 --> 01:26:27,040
OF SUM REAL THERE IS REALLY --

2452
01:26:27,040 --> 01:26:28,760
IS REACH OUT TO PROGRAM

2453
01:26:28,760 --> 01:26:31,080
OFFICIALS, SEND US AN EMAIL,

2454
01:26:31,080 --> 01:26:33,040
SEND US YOUR SPECIFIC AIMS IF

2455
01:26:33,040 --> 01:26:34,560
YOU HAVE THOUGHTS IN MIND, IN

2456
01:26:34,560 --> 01:26:38,760
GENERAL, A DRAFT OF THAT, YOUR

2457
01:26:38,760 --> 01:26:41,680
BIOSKETCH, AND WE ARE HERE TO

2458
01:26:41,680 --> 01:26:41,880
HELP.

2459
01:26:41,880 --> 01:26:43,440
>> I JUST WANT TO
REINFORCE THAT

2460
01:26:43,440 --> 01:26:44,520
FOR EVERYBODY ON THIS CALL AND

2461
01:26:44,520 --> 01:26:46,160
ANYBODY WHO MIGHT BE LISTENING,

2462
01:26:46,160 --> 01:26:48,800
PROGRAM OFFICERS AT THE NIH

2463
01:26:48,800 --> 01:26:53,400
EXIST TO TALK TO APPLICANTS AND

2464
01:26:53,400 --> 01:26:53,720
GRANTEES.

2465
01:26:53,720 --> 01:26:56,120
THAT IS WHAT OUR JOB IS.

2466
01:26:56,120 --> 01:26:58,720
SO YOU SHOULD FEEL FREE TO REACH

2467
01:26:58,720 --> 01:27:03,760
OUT EARLY AND OFTEN AND THAT IS

2468
01:27:03,760 --> 01:27:05,400
WHAT OUR TRAINING EXPERTS DO AND

2469
01:27:05,400 --> 01:27:06,760
THEN WHEN YOU GET FURTHER INTO

2470
01:27:06,760 --> 01:27:07,920
YOUR CAREER WHEN YOU'RE LOOKING

2471
01:27:07,920 --> 01:27:10,760
FOR THE R MECHANISM, THE R01s

2472
01:27:10,760 --> 01:27:14,360
AND THE R21s ABANDONS      AND ,

2473
01:27:14,360 --> 01:27:15,800
PROGRAM OFFICERS LITERALLY EXIST

2474
01:27:15,800 --> 01:27:17,640
TO HELP PEOPLE GET FUNDED, TO

2475
01:27:17,640 --> 01:27:20,280
UNDERSTAND THE SITUATION, TO

2476
01:27:20,280 --> 01:27:22,240
NAVIGATE THE BIG BLACK BOX

2477
01:27:22,240 --> 01:27:25,440
THAT'S NIH, AND IT'S WHAT WE

2478
01:27:25,440 --> 01:27:27,400
ENJOY DOING AND WE LOVE TO TALK

2479
01:27:27,400 --> 01:27:28,280
SCIENCE WITH YOU.

2480
01:27:28,280 --> 01:27:29,840
WE JUST NEED YOU TO REACH OUT TO

2481
01:27:29,840 --> 01:27:30,640
US.

2482
01:27:30,640 --> 01:27:33,960
AND BE PERSISTENT, BE PATIENT.

2483
01:27:33,960 --> 01:27:36,040
YOU MAY ALSO GET FORWARDED, AS

2484
01:27:36,040 --> 01:27:37,920
JAY SAID, IF HE'S NOT THE THE

2485
01:27:37,920 --> 01:27:38,920
RIGHT TARGET, HE WILL SEND TO

2486
01:27:38,920 --> 01:27:40,000
YOU A COLLEAGUE THAT HE THINKS

2487
01:27:40,000 --> 01:27:41,720
CAN HELP YOU BE BETTER

2488
01:27:41,720 --> 01:27:42,160
POSITIONED.

2489
01:27:42,160 --> 01:27:46,120
SO THAT IS A FUNDAMENTAL LESSON

2490
01:27:46,120 --> 01:27:47,960
THAT EVERYBODY SHOULD LEARN NO

2491
01:27:47,960 --> 01:27:50,800
MATTER WHAT CAREER STAGES, TO

2492
01:27:50,800 --> 01:27:52,440
REACH OUT TO PROGRAM OFFICERS

2493
01:27:52,440 --> 01:27:55,200
ACROSS THE DIFFERENT INSTITUTES

2494
01:27:55,200 --> 01:28:01,520
AND ALLOW THEM TO ASSIST YOU.

2495
01:28:01,520 --> 01:28:02,960
HOW ARE WE DOING FOR TIME?

2496
01:28:02,960 --> 01:28:05,240
I KNOW WE'RE WRAPPING UP IN JUST

2497
01:28:05,240 --> 01:28:05,880
A LITTLE BIT.

2498
01:28:05,880 --> 01:28:07,000
THERE WERE A COUPLE MORE

2499
01:28:07,000 --> 01:28:08,400
QUESTIONS IN THE CHAT, JAY.

2500
01:28:08,400 --> 01:28:10,160
WE HAVE A 2-MINUTE WARNING.

2501
01:28:10,160 --> 01:28:11,600
IF WE CAN GET TO THOSE SO THAT

2502
01:28:11,600 --> 01:28:12,480
THOSE INDIVIDUALS GET THEIR

2503
01:28:12,480 --> 01:28:14,320
QUESTIONS ANSWERED, SO I'LL DO

2504
01:28:14,320 --> 01:28:18,120
THE FIRST ONE THAT IS TO

2505
01:28:18,120 --> 01:28:19,360
DR. PEDEGO AGAIN.

2506
01:28:19,360 --> 01:28:21,440
WHAT METHOD ARE YOU USING TO

2507
01:28:21,440 --> 01:28:24,040
FIND THE, QUOTE-UNQUOTE,

2508
01:28:24,040 --> 01:28:25,560
NETWORKS?

2509
01:28:25,560 --> 01:28:28,760
AND WHAT DATA ARE -- SORRY, AND

2510
01:28:28,760 --> 01:28:30,040
WHAT DATA PROVIDE THE STARTING

2511
01:28:30,040 --> 01:28:30,240
POINT?

2512
01:28:30,240 --> 01:28:31,640
SO IF YOU HAVE A QUICK ANSWER TO

2513
01:28:31,640 --> 01:28:32,680
THAT, THEN WE'LL GET TO THE LAST

2514
01:28:32,680 --> 01:28:33,240
QUESTION WE HAVE.

2515
01:28:33,240 --> 01:28:36,640
>> YEAH, VERY QUICKLY,
IT'S

2516
01:28:36,640 --> 01:28:37,840
ELECTRON MICROSCOPY DATA, SO

2517
01:28:37,840 --> 01:28:39,600
IT'S PURELY BASED ON THE

2518
01:28:39,600 --> 01:28:41,880
STRUCTURE AND SYNAPSES THAT

2519
01:28:41,880 --> 01:28:43,200
PEOPLE OBSERVE IN THOSE IMAGES

2520
01:28:43,200 --> 01:28:45,080
AND THEN THE RECONSTRUCTION IS

2521
01:28:45,080 --> 01:28:50,680
DONE VIA MANUAL TRACING.

2522
01:28:50,680 --> 01:28:51,840
>> GREAT, THANKS.

2523
01:28:51,840 --> 01:28:52,960
MAYBE AS A GOOD BOOK END,

2524
01:28:52,960 --> 01:28:53,920
BECAUSE I BELIEVE THE FIRST

2525
01:28:53,920 --> 01:28:56,200
QUESTION WAS FOR DESIREE, WE'RE

2526
01:28:56,200 --> 01:28:57,680
GOING TO SEND THE LAST QUESTION

2527
01:28:57,680 --> 01:28:58,200
AS WELL.

2528
01:28:58,200 --> 01:28:59,320
THERE'S A COUPLE PIECES TO THIS.

2529
01:28:59,320 --> 01:29:04,080
I'LL TUMP ON      CAN YOU COMMEF

2530
01:29:04,080 --> 01:29:06,400
INACTIVATIONS ON THE PHOTO

2531
01:29:06,400 --> 01:29:07,680
ACTIVATED OXYMORPHINE OR ANY

2532
01:29:07,680 --> 01:29:09,320
OTHER LONG-ACTING OR EXTENDED

2533
01:29:09,320 --> 01:29:10,000
RELEASE MEDICATIONS THAT YOU

2534
01:29:10,000 --> 01:29:11,000
HAVE USED?

2535
01:29:11,000 --> 01:29:14,600
>> YEAH, SO QUICK ANSWER
TO

2536
01:29:14,600 --> 01:29:17,080
THIS, CURRENTLY WITH THE IN VIVO

2537
01:29:17,080 --> 01:29:19,080
DATA THAT IS SHOWN LIKE ON MY

2538
01:29:19,080 --> 01:29:22,240
POSTER, YOU SEE THAT BOX, PHOTO

2539
01:29:22,240 --> 01:29:23,440
ACTIVATION LASTS TENS OF MINUTES

2540
01:29:23,440 --> 01:29:25,760
IN OUR IN VIVO DATA, BUT IN THE

2541
01:29:25,760 --> 01:29:28,040
FUTURE, WE'RE TRYING TO OPTIMIZE

2542
01:29:28,040 --> 01:29:30,960
OUR DOSE CONCENTRATION LIGHT

2543
01:29:30,960 --> 01:29:33,600
USAGE SO THAT WE CAN HAVE, YOU

2544
01:29:33,600 --> 01:29:36,480
KNOW, QUICKER OFFERING

2545
01:29:36,480 --> 01:29:38,320
ESSENTIALLY TO LOOK AT, JUST

2546
01:29:38,320 --> 01:29:43,440
MORE SENSITIVE BEHAVIORS AND

2547
01:29:43,440 --> 01:29:46,440
NEUROMECHANISMS.

2548
01:29:46,440 --> 01:29:47,080
>> GREAT.

2549
01:29:47,080 --> 01:29:48,840
SHALL I TAKE A STAB, JAY, REAL

2550
01:29:48,840 --> 01:29:49,040
QUICK?

2551
01:29:49,040 --> 01:29:49,280
>> PLEASE.

2552
01:29:49,280 --> 01:29:50,800
>> I WANT TO THANK
EVERYBODY FOR

2553
01:29:50,800 --> 01:29:52,000
THEIR TALKS TODAY.

2554
01:29:52,000 --> 01:29:53,080
IT WAS REALLY GREAT.

2555
01:29:53,080 --> 01:29:54,320
WE CAN'T WAIT TO SEE WHAT YOU

2556
01:29:54,320 --> 01:29:55,840
BRING TO US IN THE FUTURE AND

2557
01:29:55,840 --> 01:29:57,080
WHAT YOUR FUTURE HOLDS FOR ALL

2558
01:29:57,080 --> 01:29:57,920
OF YOU.

2559
01:29:57,920 --> 01:29:59,120
WE APPRECIATE IT, EVERYBODY GO

2560
01:29:59,120 --> 01:30:00,640
CHECK OUT THE POSTERS, AND WE

2561
01:30:00,640 --> 01:30:01,520
LOOK FORWARD TO THE REST OF THE

2562
01:30:01,520 --> 01:30:03,920
MEETING.

2563
01:30:03,920 --> 01:30:04,760
THANK YOU.

2564
01:30:04,760 --> 01:30:07,640
>>HELLO, AND WELCOME TO
THE

2565
01:30:07,640 --> 01:30:09,360
SYMPOSIUM, ADVANCING OUR

2566
01:30:09,360 --> 01:30:11,000
UNDERSTANDING OF THE BRAIN AND

2567
01:30:11,000 --> 01:30:13,760
BEHAVIOR THROUGH CONNECTOMICS.

2568
01:30:13,760 --> 01:30:17,600
TODAY WE HAVE SIX TALKS AND I'LL

2569
01:30:17,600 --> 01:30:20,440
BRIEFLY INTRODUCE THE SPEAKERS

2570
01:30:20,440 --> 01:30:21,040
TODAY.

2571
01:30:21,040 --> 01:30:25,160
BEN MULCAHY FROM THE LONDON FELD

2572
01:30:25,160 --> 01:30:27,120
RESEARCH INSTITUTED IN TORONTO,

2573
01:30:27,120 --> 01:30:29,080
SPEAKING NEXT WILL BE CLAIRE

2574
01:30:29,080 --> 01:30:34,360
MCKELLAR FROM FLY WAIR, I WILL

2575
01:30:34,360 --> 01:30:36,760
BE FOLLOWING CLAIRE, MY NAME IS

2576
01:30:36,760 --> 01:30:40,760
WEI-CHUNG LEE BOSTON CHILDREN'S

2577
01:30:40,760 --> 01:30:42,600
HOSPITAL AND HARVARD MEDICAL

2578
01:30:42,600 --> 01:30:42,840
SCHOOL.

2579
01:30:42,840 --> 01:30:44,600
FOLLOWING ME WILL BE STEPHANIE

2580
01:30:44,600 --> 01:30:45,800
HAMPEL FROM THE UNIVERSITY OF

2581
01:30:45,800 --> 01:30:47,200
PUERTO RICO AND FOLLOWING

2582
01:30:47,200 --> 01:30:49,320
STEPHANIE WILL BE MICHAEL REISER

2583
01:30:49,320 --> 01:30:51,800
FROM HOWARD HUGHES MEDICAL

2584
01:30:51,800 --> 01:30:53,480
INSTITUTE -- RESEARCH CAMPUS.

2585
01:30:53,480 --> 01:30:58,280
FINALLY, WE'LL HAVE SETH GRANT

2586
01:30:58,280 --> 01:31:02,240
FROM EDENBUROUGH UNIVERSITY AND

2587
01:31:02,240 --> 01:31:03,280
FOLLOWING SIX TALKS WE'LL HAVE

2588
01:31:03,280 --> 01:31:06,320
TEN TO FIFTEEN MINUTE

2589
01:31:06,320 --> 01:31:07,160
QUESTION-AND-ANSWER SESSION WITH

2590
01:31:07,160 --> 01:31:09,600
MOST OF THE SPEAKERS.

2591
01:31:09,600 --> 01:31:14,280
SO WE WILL START WITH BEN.

2592
01:31:14,280 --> 01:31:15,160
>> GREAT.

2593
01:31:15,160 --> 01:31:17,160
THANKS TO THE ORGANIZERS FOR

2594
01:31:17,160 --> 01:31:20,360
INVITING ME TO SPEAK TODAY.

2595
01:31:20,360 --> 01:31:23,400
I'M BASED IN TORONTO AND FOR THE

2596
01:31:23,400 --> 01:31:24,600
LAST FEW YEARS I'VE BEEN TRYING

2597
01:31:24,600 --> 01:31:27,040
TO UNDERSTAND HOW NEURO CIRCUITS

2598
01:31:27,040 --> 01:31:28,640
MODULE AFTER US, SO THESE

2599
01:31:28,640 --> 01:31:31,400
MODELING CIRCUITS ARE WIDESPREAD

2600
01:31:31,400 --> 01:31:33,040
ACROSS, THEY INCLUDE THE BIRTH

2601
01:31:33,040 --> 01:31:35,080
OF NEW NEURONS WHICH HAVE TO GO

2602
01:31:35,080 --> 01:31:36,520
THROUGH PROCESSES AND INTEGRATE

2603
01:31:36,520 --> 01:31:38,080
INTO EXISTING CIRCUITRY AND

2604
01:31:38,080 --> 01:31:39,360
JUVENILE CIRCUITS THAT HAVE TO

2605
01:31:39,360 --> 01:31:43,120
REWIRE TO ACCOMMODATE NEURONS OR

2606
01:31:43,120 --> 01:31:44,880
MODIFY THEIR PROPERTIES AND AS

2607
01:31:44,880 --> 01:31:46,400
THIS REMODELING TAKES PLACE,

2608
01:31:46,400 --> 01:31:47,400
CIRCUITS STILL HAVE TO BE ABLE

2609
01:31:47,400 --> 01:31:53,600
TO WORK WITHOUT BEING DISRUPTED.

2610
01:31:53,600 --> 01:31:55,560
C HE WILL GAFNS DOES THIS VERY

2611
01:31:55,560 --> 01:31:57,680
WELL AND REHATCHES THROUGH 220

2612
01:31:57,680 --> 01:31:59,480
NEURONS AND INCREASES THIS

2613
01:31:59,480 --> 01:32:01,000
NUMBER TO 302.

2614
01:32:01,000 --> 01:32:03,760
MOST OF THESE NEW NEURONS ARE

2615
01:32:03,760 --> 01:32:05,960
MOARTD NEURONS EXPANDING THE

2616
01:32:05,960 --> 01:32:08,720
MOLARITY NEURON POOL FROM 22 TO

2617
01:32:08,720 --> 01:32:10,320
75 METANEURONS AS WELL AS

2618
01:32:10,320 --> 01:32:11,720
INCREASING THE NUMBER OF

2619
01:32:11,720 --> 01:32:13,000
METANEURON CROSSES.

2620
01:32:13,000 --> 01:32:14,920
IN THE FIRST STAGE C. ELEGANS

2621
01:32:14,920 --> 01:32:18,720
HAS THIS ASYMMETRIC, HAS TWO

2622
01:32:18,720 --> 01:32:22,600
CLASSES OF NEURONS TO CONTRACT

2623
01:32:22,600 --> 01:32:24,320
DORSAL MUSCLES AND THIS ALSO

2624
01:32:24,320 --> 01:32:26,200
ACTIVATES THESE INHIBITOR

2625
01:32:26,200 --> 01:32:28,080
NEURONS WHICH SIGNAL ALONG THE

2626
01:32:28,080 --> 01:32:30,160
PROCESS TO REALLY SCAMPER TO

2627
01:32:30,160 --> 01:32:33,120
INHIBIT VENTRALS, SO YOU HAVE

2628
01:32:33,120 --> 01:32:35,640
THIS EXCITATION OF DORSAL

2629
01:32:35,640 --> 01:32:37,360
MUSCLE, RELAXATION OF VENTRAL SO

2630
01:32:37,360 --> 01:32:41,480
YOU GET BENDING.

2631
01:32:41,480 --> 01:32:42,840
9 SICIALGHT HAS EXPANDED WITH

2632
01:32:42,840 --> 01:32:45,280
ALL OF THESE NEW CAUSES OF

2633
01:32:45,280 --> 01:32:46,120
METANEURONS AND IT'S BECOME

2634
01:32:46,120 --> 01:32:48,120
SYMMETRIC AND THIS ISN'T JUST

2635
01:32:48,120 --> 01:32:49,440
DUE TOLT ADDITION OF

2636
01:32:49,440 --> 01:32:51,520
FUNCTIONALITY BY THE NEW NEURONS

2637
01:32:51,520 --> 01:32:53,720
BUT ALSO REMODELING OF THE

2638
01:32:53,720 --> 01:32:56,680
JUVENILE METANEURONS, SO THE

2639
01:32:56,680 --> 01:32:59,320
METANEURONS THAT INHIBITED

2640
01:32:59,320 --> 01:33:02,720
METANUFLS IN JUVENILE ANIMALS

2641
01:33:02,720 --> 01:33:04,440
SWAWL POLAR TAKE AND JUVENILE

2642
01:33:04,440 --> 01:33:07,280
ROLE IS TAKEN OVER BY THESE

2643
01:33:07,280 --> 01:33:09,840
NEWBORN INHIBITORY NEURONS WHICH

2644
01:33:09,840 --> 01:33:11,800
GROW OUT AND COPY THEIR WIRING

2645
01:33:11,800 --> 01:33:12,440
PATTERN.

2646
01:33:12,440 --> 01:33:14,280
REMARKABLY THIS HAPPENS WITHOUT

2647
01:33:14,280 --> 01:33:16,280
DISRUPTING CIRCUIT OUTPUT.

2648
01:33:16,280 --> 01:33:17,680
C. ELEGANS IS ABLE TO MOVE

2649
01:33:17,680 --> 01:33:20,000
AROUND HAPPILY BEFORE, DURING

2650
01:33:20,000 --> 01:33:21,760
AND AFTER MOTOR REMODELING.

2651
01:33:21,760 --> 01:33:23,720
SO IF WE TRACK ANIMALS MOVING

2652
01:33:23,720 --> 01:33:25,800
AROUND THE PLATE AND EXPRESS G

2653
01:33:25,800 --> 01:33:27,560
CAMP AND MUSCLE CELLS WE CAN SEE

2654
01:33:27,560 --> 01:33:29,520
THEY MOVE AROUND WELL WITH BODY

2655
01:33:29,520 --> 01:33:30,600
BENDING WAVES THAT TRAVEL FROM

2656
01:33:30,600 --> 01:33:33,240
THE HEAD TO THE TAIL, ON THE

2657
01:33:33,240 --> 01:33:35,120
BODY, AND VENTRAL AND DORSAL

2658
01:33:35,120 --> 01:33:36,120
CALCIUM WAVES OF THE MUSCLES

2659
01:33:36,120 --> 01:33:39,320
THAT CORRELATE WITH THE BENDING

2660
01:33:39,320 --> 01:33:40,960
NICELY.

2661
01:33:40,960 --> 01:33:44,120
VENTRAL AND DORSAL CALCIUM ARE

2662
01:33:44,120 --> 01:33:45,040
ANTI-CORRELATED, THIS IS THE

2663
01:33:45,040 --> 01:33:46,720
CASE AT THE BEGINNING, MIDDLE

2664
01:33:46,720 --> 01:33:48,080
AND END OF MODELING AS YOU CAN

2665
01:33:48,080 --> 01:33:50,280
SEE FROM THIS HISTOGRAM WHERE

2666
01:33:50,280 --> 01:33:52,120
VENTRAL AND DORSAL CALCIUM

2667
01:33:52,120 --> 01:33:55,320
ACTIVITY IN RED AND BLUE IS

2668
01:33:55,320 --> 01:34:01,960
180 DEGREES OU OF PHASE, BUT

2669
01:34:01,960 --> 01:34:03,800
180 DEGREES, SO TO UNDERSTAND

2670
01:34:03,800 --> 01:34:05,680
HOW THIS CIRCUIT REMODELS

2671
01:34:05,680 --> 01:34:07,000
WITHOUT DISRUPTING MOTOR ABILITY

2672
01:34:07,000 --> 01:34:10,080
WE DECIDED TO LOOK AT THE OLDER

2673
01:34:10,080 --> 01:34:12,040
STRUCTURE OF THE METACIRCUIT AS

2674
01:34:12,040 --> 01:34:13,200
IT REMODELS.

2675
01:34:13,200 --> 01:34:17,640
TO DO THIS, WE DID ZEER --

2676
01:34:17,640 --> 01:34:19,040
ELECTRON MIE CROSS SWOPE BEFORE,

2677
01:34:19,040 --> 01:34:21,680
DURING AND AFTER REMODELING AND

2678
01:34:21,680 --> 01:34:23,200
FIRST COVERED THE WHOLE BODY,

2679
01:34:23,200 --> 01:34:25,560
NOSE TO TAIL, THEN WE REALIZED

2680
01:34:25,560 --> 01:34:27,000
THIS IS ACTUAL A LOT OF WORK AND

2681
01:34:27,000 --> 01:34:28,560
EVERYTHING IS REPEATED ALONG THE

2682
01:34:28,560 --> 01:34:31,200
BODY ANALYSIS ANYWAY SO THE LAST

2683
01:34:31,200 --> 01:34:32,840
TWO RECONSTRUCTIONS FOCUS ODD

2684
01:34:32,840 --> 01:34:34,520
THEIR ANTERIOR BODY AND INCLUDED

2685
01:34:34,520 --> 01:34:38,120
THE ENTIRE BODY DD1 AND 2 AND

2686
01:34:38,120 --> 01:34:40,200
BECAUSE THE DEVELOPMENTAL

2687
01:34:40,200 --> 01:34:42,040
TIMELINE AND C. ELEGANS

2688
01:34:42,040 --> 01:34:43,600
STEREOTYPES THIS MEANS THAT BY

2689
01:34:43,600 --> 01:34:45,560
LOOKING AT DIFFERENT INDIVIDUALS

2690
01:34:45,560 --> 01:34:46,440
AT SEQUENTIAL DEVELOPMENTAL

2691
01:34:46,440 --> 01:34:48,200
STAGES WE ESSENTIALLY END UP

2692
01:34:48,200 --> 01:34:51,800
WITH A TIME MAX OF REMODELING

2693
01:34:51,800 --> 01:34:52,880
ACROSS DEVELOPMENT AND NOT ONLY

2694
01:34:52,880 --> 01:34:56,040
THAT BUT YOU MIGHT SEE FROM THIS

2695
01:34:56,040 --> 01:34:57,920
RECONSTRUCTION OF THE NEW

2696
01:34:57,920 --> 01:34:59,920
INHIBITORY THAT MIDWAY THROUGH

2697
01:34:59,920 --> 01:35:01,680
OUTGROWTH THE ANTERIOR NEURONS

2698
01:35:01,680 --> 01:35:03,720
ARE MORE ADVANCED STAGE OF OUTER

2699
01:35:03,720 --> 01:35:05,280
GROWTH THAN THE POSTERIOR ONES

2700
01:35:05,280 --> 01:35:07,360
AND THIS FOLLOWS THE BIRTH ORDER

2701
01:35:07,360 --> 01:35:08,680
OF THE NEURONS SO WE HAVE THIS

2702
01:35:08,680 --> 01:35:10,080
TIME LAPSE BETWEEN INDIVIDUALS

2703
01:35:10,080 --> 01:35:15,240
AND WITHIN INDIVIDUALS.

2704
01:35:15,240 --> 01:35:16,640
THE FIRST THING WE SAW WHEN WE

2705
01:35:16,640 --> 01:35:18,200
LOOKED AT THE DATA WAS THAT

2706
01:35:18,200 --> 01:35:20,920
PROCESS OUTGROWTH WAS VERY

2707
01:35:20,920 --> 01:35:23,040
INTERACTIVE SO AT THIS TIME

2708
01:35:23,040 --> 01:35:24,560
POINT IN THE FIRST LARVA STAGE

2709
01:35:24,560 --> 01:35:26,760
WE HAVE CAUGHT THIS NEWBORN

2710
01:35:26,760 --> 01:35:28,080
INHIBITORY MOTOR NEURON HALFWAY

2711
01:35:28,080 --> 01:35:31,680
THROUGH THE OUTGROWTH OF ITS

2712
01:35:31,680 --> 01:35:31,920
PROCESS.

2713
01:35:31,920 --> 01:35:33,760
IF YOU TAKE A CROSS-SECTION

2714
01:35:33,760 --> 01:35:34,520
THROUGH THIS COMMISSION WHAT YOU

2715
01:35:34,520 --> 01:35:36,720
SEE IS THE NEWBORN NEURONS

2716
01:35:36,720 --> 01:35:39,480
WRAPPING AROUND THIS EXISTING

2717
01:35:39,480 --> 01:35:40,320
COMMISSION BUNDLE.

2718
01:35:40,320 --> 01:35:41,760
THEN IF YOU LOOK ONE HOUR LATER

2719
01:35:41,760 --> 01:35:44,280
AFTER NEURONS REACH THE DORSAL

2720
01:35:44,280 --> 01:35:46,760
COURT, YOU SEE IT'S NOW THE

2721
01:35:46,760 --> 01:35:49,000
DORSAL PROCESS THAT IS WRAPPING

2722
01:35:49,000 --> 01:35:50,400
AROUND EXISTING NEURONS

2723
01:35:50,400 --> 01:35:52,160
ESPECIALLY JUVENILE INHIBITORY

2724
01:35:52,160 --> 01:35:56,080
MOTOR NEURONS, AND FINALLY AFTER

2725
01:35:56,080 --> 01:35:57,520
OUTGROWTH IS COMPLETE, YOU SEE

2726
01:35:57,520 --> 01:36:00,680
THE NEURO NEURONS ARE RUNNING IN

2727
01:36:00,680 --> 01:36:02,240
PARALLEL AND YOU HAVE THIS

2728
01:36:02,240 --> 01:36:03,320
MORPHOLOGY THAT ISN'T WRAPPING

2729
01:36:03,320 --> 01:36:06,840
AROUND EXISTING STRUCTURES

2730
01:36:06,840 --> 01:36:07,160
ANYMORE.

2731
01:36:07,160 --> 01:36:08,120
SO WE HAVE THIS SEQUENTIAL

2732
01:36:08,120 --> 01:36:10,440
WRAPPING AND UNWRAPPING AROUND

2733
01:36:10,440 --> 01:36:12,520
THE INHIBITORY MOTOR NEURONS

2734
01:36:12,520 --> 01:36:14,520
THAT OCCURS DURING JOAT GROWTH

2735
01:36:14,520 --> 01:36:16,400
LIKELY HELPING TO GUIDE THE

2736
01:36:16,400 --> 01:36:19,600
NEWBORN NEURONS TO PROCESS

2737
01:36:19,600 --> 01:36:22,400
PLACEMENT.

2738
01:36:22,400 --> 01:36:24,120
IF YOU LOOK AT THEIR

2739
01:36:24,120 --> 01:36:26,000
CONNECTIVITY YOU SEE THE NEWBORN

2740
01:36:26,000 --> 01:36:27,960
NEURONS START TO FIRE UP DURING

2741
01:36:27,960 --> 01:36:28,440
OUTGROWTH.

2742
01:36:28,440 --> 01:36:29,720
SO HERE WE HAVE RECONSTRUCTION

2743
01:36:29,720 --> 01:36:34,280
OF THE B -- VD3 NEURON HALFWAY

2744
01:36:34,280 --> 01:36:36,680
THROUGH THE OUTGROWTH.

2745
01:36:36,680 --> 01:36:39,080
MATURING NEURONS ON LEFT,

2746
01:36:39,080 --> 01:36:41,960
RECEIVES INPUTTED AND NEW

2747
01:36:41,960 --> 01:36:43,600
MUSCULAR JUNCTIONS BUT DOESN'T

2748
01:36:43,600 --> 01:36:45,480
HAVE ANY INPUTTED F WE TAKE A

2749
01:36:45,480 --> 01:36:46,440
CROSS-SECTION THROUGH THE

2750
01:36:46,440 --> 01:36:48,520
VENTRAL PROCESS WE SEE A SYNAPSE

2751
01:36:48,520 --> 01:36:50,040
IN THE PROCESS OF ESTABLISHING

2752
01:36:50,040 --> 01:36:52,920
ICHTS THAT HAS A PRESYNAPTIC

2753
01:36:52,920 --> 01:36:53,880
PROJECTION POINTING TOWARDS

2754
01:36:53,880 --> 01:36:56,400
MUSCLE CELL AND IT DOESN'T YET

2755
01:36:56,400 --> 01:36:58,160
HAVE AN ESTABLISHED BASE CORE

2756
01:36:58,160 --> 01:37:00,320
COWBTD AND AS TIME GOES ON,

2757
01:37:00,320 --> 01:37:02,760
RECRUITED AND SYNAPSE BECOMES

2758
01:37:02,760 --> 01:37:03,080
MATURE.

2759
01:37:03,080 --> 01:37:05,920
SO SYNAPSE GENESIS OCCURS DURING

2760
01:37:05,920 --> 01:37:07,560
OUTGROWTH OF THESE NEW NEURONS

2761
01:37:07,560 --> 01:37:10,200
AND IT'S VERY LIKELY A HARD

2762
01:37:10,200 --> 01:37:11,160
HARDWIRED PROCESS THAT BEGINS

2763
01:37:11,160 --> 01:37:13,480
WITHOUT ANY VENTRICULAR

2764
01:37:13,480 --> 01:37:13,880
COMPONENT.

2765
01:37:13,880 --> 01:37:15,560
NOW F WE LOOK AT THE CONNECTED

2766
01:37:15,560 --> 01:37:18,320
ACTIVITY OF THE JUVENILE MOTOR

2767
01:37:18,320 --> 01:37:19,840
NEURONS WE SEE THAT EARLY IN THE

2768
01:37:19,840 --> 01:37:22,240
FIRST LARVAL STAGE AS EXPECTED

2769
01:37:22,240 --> 01:37:25,200
THEY RECEIVED DORSAL INPUT AND

2770
01:37:25,200 --> 01:37:28,280
MAKE DORSAL NEW JUNCTIONS.

2771
01:37:28,280 --> 01:37:29,400
SAYS AFTER REMODELING THIS

2772
01:37:29,400 --> 01:37:30,880
PATTERN IS REVERSED, THEY

2773
01:37:30,880 --> 01:37:33,280
RECEIVE VENTRAL INPUT AND MAKE

2774
01:37:33,280 --> 01:37:35,160
NEW MUSCULAR JUNCTIONS TO DORSAL

2775
01:37:35,160 --> 01:37:36,160
MUSCLE CELLS.

2776
01:37:36,160 --> 01:37:39,000
IN THE MIDDLE OF THIS REMODELING

2777
01:37:39,000 --> 01:37:40,640
THEIR POLARITY IS MIXED, THEY

2778
01:37:40,640 --> 01:37:42,400
GET INPUT ON BOTH THE VENTRAL

2779
01:37:42,400 --> 01:37:43,920
AND DORSAL SIDES AND MAKE NEW

2780
01:37:43,920 --> 01:37:46,760
MUSCULAR JUNCTIONS TO BOTH SIDES

2781
01:37:46,760 --> 01:37:47,080
TOO.

2782
01:37:47,080 --> 01:37:50,400
ONE MIGHT EXPECT THAT THIS WOULD

2783
01:37:50,400 --> 01:37:52,720
DISRUPTED CIRCUITRY IN THE MOTOR

2784
01:37:52,720 --> 01:37:55,280
BUT DON'T SEE THIS DISRUPTION IN

2785
01:37:55,280 --> 01:37:56,080
THE BEHAVIOR.

2786
01:37:56,080 --> 01:37:58,480
WE LOOK AT CLUSTERING IN MUSCLE

2787
01:37:58,480 --> 01:37:59,360
CELLS AND EARLY IN DEVELOPMENT

2788
01:37:59,360 --> 01:38:01,120
WE SEE THEM ONLY ON THE VENTRAL

2789
01:38:01,120 --> 01:38:02,600
SIDE OF THE ANIMAL CONSISTENT

2790
01:38:02,600 --> 01:38:06,600
WITH THE CONNECTIVITY AND AFTER

2791
01:38:06,600 --> 01:38:08,240
REMODELING WE SEE THEM ON BOTH

2792
01:38:08,240 --> 01:38:12,000
VENTRAL AND DORSAL SIDES.

2793
01:38:12,000 --> 01:38:14,000
AND WHEN WE LOOK DURING MODELING

2794
01:38:14,000 --> 01:38:15,600
WE START TO SEE THE APPEARANCE

2795
01:38:15,600 --> 01:38:18,000
OF THESE FAINT CLUSTERS ABOUT

2796
01:38:18,000 --> 01:38:20,080
THE SAME KIND OF TIME AS WE

2797
01:38:20,080 --> 01:38:22,400
START TO SEE SYNAPSES APPEARING

2798
01:38:22,400 --> 01:38:24,360
IN THE ELECTROMICROSCOPY POINTS,

2799
01:38:24,360 --> 01:38:26,720
THEY'RE WEAK AND THEY APPEAR IN

2800
01:38:26,720 --> 01:38:27,960
THE ANTERIOR BODY FIRST AND THEN

2801
01:38:27,960 --> 01:38:31,560
THEY PROGRESS ALONG THE

2802
01:38:31,560 --> 01:38:32,160
POSTERIOR.

2803
01:38:32,160 --> 01:38:36,720
SO WE HAVE THIS JUVENILE MOTOR

2804
01:38:36,720 --> 01:38:38,360
CIRCUIT NEW NEURONS AND

2805
01:38:38,360 --> 01:38:39,880
REMODELING EXISTING ONES AS IT

2806
01:38:39,880 --> 01:38:42,080
SWITCHES FROM JUVENILE TO MATURE

2807
01:38:42,080 --> 01:38:42,520
CONFIGURATION.

2808
01:38:42,520 --> 01:38:44,400
DURING THE REMODELING WE SEE

2809
01:38:44,400 --> 01:38:46,440
THIS GRADUAL BUILDUP OF THE

2810
01:38:46,440 --> 01:38:48,080
MATURE CIRCUITED TRI WHILE

2811
01:38:48,080 --> 01:38:48,800
MAINTAINING THE JUVENILE

2812
01:38:48,800 --> 01:38:50,280
CONNECTIONS AND IT'S ONLY AFTER

2813
01:38:50,280 --> 01:38:52,120
EVERYTHING IS BUILT UP THAT THE

2814
01:38:52,120 --> 01:38:54,040
JUVENILE CONNECTIONS ARE

2815
01:38:54,040 --> 01:38:55,240
DISASSEMBLED AND THE CIRCUIT

2816
01:38:55,240 --> 01:38:56,960
SWICHEDZ FROM THE JUVENILE TO

2817
01:38:56,960 --> 01:39:00,280
MATURE INTEGRATION.

2818
01:39:00,280 --> 01:39:02,760
THIS IS STAGGERED ALONG THE

2819
01:39:02,760 --> 01:39:04,200
ANTERIOR POSTERIOR ACCESS

2820
01:39:04,200 --> 01:39:05,840
FOLLOWING THE BIRTH ORDER OF THE

2821
01:39:05,840 --> 01:39:06,160
NEURONS.

2822
01:39:06,160 --> 01:39:07,960
SO TOGETHER THIS GRADUAL BUILDUP

2823
01:39:07,960 --> 01:39:10,440
OF NEW CONNECTIVITY AND THE

2824
01:39:10,440 --> 01:39:12,320
SWITCH ALONG WITH STAGGERED

2825
01:39:12,320 --> 01:39:15,240
REMODELING LOONG THE BODY AXIS

2826
01:39:15,240 --> 01:39:17,240
LIKELY HELPS ONE TO REMODEL ILTS

2827
01:39:17,240 --> 01:39:20,720
MOTOR CIRCUIT WITHOUT DISRUPTING

2828
01:39:20,720 --> 01:39:23,360
MOTOR COMMISSION.

2829
01:39:23,360 --> 01:39:25,440
LASTLY THIS SYSTEM TAKES A VERY

2830
01:39:25,440 --> 01:39:27,720
DIFFERENT APPROACH TO MATURATION

2831
01:39:27,720 --> 01:39:29,480
COMPARED TO CENTRAL NERVOUS

2832
01:39:29,480 --> 01:39:29,800
SYSTEM.

2833
01:39:29,800 --> 01:39:33,200
DANIEL IN OUR LAB SHOWED THAT

2834
01:39:33,200 --> 01:39:36,040
CNS LARGELY BUILT BY BIRTH AND

2835
01:39:36,040 --> 01:39:37,240
MAINTAINED ACROSS MATURATION

2836
01:39:37,240 --> 01:39:38,680
WITH WIRING CHANGES HAPPENING

2837
01:39:38,680 --> 01:39:40,600
ALONG THIS CONSTANT SCAFFOLD.

2838
01:39:40,600 --> 01:39:43,040
THE BIRTH SYSTEM UNDERGOES THIS

2839
01:39:43,040 --> 01:39:45,760
WIDE SCALE REMODELING OF ITS

2840
01:39:45,760 --> 01:39:47,000
STRUCTURE, WIRING AND ITS

2841
01:39:47,000 --> 01:39:48,280
COMPLEMENTED NEURONS, SO

2842
01:39:48,280 --> 01:39:49,840
DIFFERENT PARTS OF THE NERVOUS

2843
01:39:49,840 --> 01:39:51,040
SAM CONTAIN VERY DIFFERENT

2844
01:39:51,040 --> 01:39:52,400
APPROACHES TO REMODELING AND IF

2845
01:39:52,400 --> 01:39:53,520
YOU WOULD LIKE TO READ MORE

2846
01:39:53,520 --> 01:39:59,240
ABOUT THIS STORY, IT'S UP ON THE

2847
01:39:59,240 --> 01:40:02,400
BIORX PAGE.

2848
01:40:02,400 --> 01:40:04,920
THANKS FOR EVERYBODY INVOLVED,

2849
01:40:04,920 --> 01:40:09,520
AND TO THE NIH AND C HFR FOR

2850
01:40:09,520 --> 01:40:09,760
FUNGSD.

2851
01:40:09,760 --> 01:40:12,000
>> I'M CLAIRE MCKELLAR
DIRECTOR

2852
01:40:12,000 --> 01:40:13,000
OF OPERATIONS AND COMMUNITY FOR

2853
01:40:13,000 --> 01:40:14,880
FLY WIRE OPEN SCIENCE PROJECT AT

2854
01:40:14,880 --> 01:40:15,160
PRINCETON.

2855
01:40:15,160 --> 01:40:16,760
FLY WIRE IS A HUMAN AI

2856
01:40:16,760 --> 01:40:19,040
COLLABORATION TO MAP THE FLY

2857
01:40:19,040 --> 01:40:22,240
CONNECT TOMORROW, PI'S ARE IS HE

2858
01:40:22,240 --> 01:40:24,880
BASS STAN AND MALLA MUR MURPHY.

2859
01:40:24,880 --> 01:40:26,400
SOME OF THE LARGER PROJECTS IN

2860
01:40:26,400 --> 01:40:28,880
THE FLY BRAIN THE LARVA WHERE IT

2861
01:40:28,880 --> 01:40:32,200
MANUALLY RECONSTRUCTED CONNECT

2862
01:40:32,200 --> 01:40:36,680
TOMORROW OF THE WHOLE --

2863
01:40:36,680 --> 01:40:38,320
CONNECTOME, HEMIBRAIN, PART OF

2864
01:40:38,320 --> 01:40:40,080
ADULT CENTRAL BRAIN, IMAGE

2865
01:40:40,080 --> 01:40:44,680
DATASET OF FULL FEMALE ADULT FLY

2866
01:40:44,680 --> 01:40:46,160
BRAIN AVAILABLE?

2867
01:40:46,160 --> 01:40:48,480
IS WALLED GARDEN ENVIRONMENT

2868
01:40:48,480 --> 01:40:50,120
WHERE MEMBERS CAN MANUALLY

2869
01:40:50,120 --> 01:40:52,360
RECONSTRUCT NEURONS AND FLY WIRE

2870
01:40:52,360 --> 01:40:56,720
USES THE SAME IMAGE FLY SET BUT

2871
01:40:56,720 --> 01:40:59,040
NEURONS RECONSTRUCTED BY OUR AI

2872
01:40:59,040 --> 01:41:00,320
AND PROOFREAD BY AN OPEN

2873
01:41:00,320 --> 01:41:02,080
COMMUNITY OF FLY BIOLOGISTS AND

2874
01:41:02,080 --> 01:41:02,440
OTHERS.

2875
01:41:02,440 --> 01:41:04,160
THE GOAL OF FLY WIRE IS TO

2876
01:41:04,160 --> 01:41:07,560
CROWDSOURCE A WHOLE BRAIN

2877
01:41:07,560 --> 01:41:10,320
CONNECTOME FOR THE ADULT.

2878
01:41:10,320 --> 01:41:12,640
USED TRANSMISSION ELECTRON

2879
01:41:12,640 --> 01:41:16,440
MICROSCOPE ON AS STACK OF 7,000

2880
01:41:16,440 --> 01:41:19,240
SECTIONS, DATA SET OF 21 MILLION

2881
01:41:19,240 --> 01:41:19,800
CAMERA IMAGES.

2882
01:41:19,800 --> 01:41:21,360
AT PRINCE DONE WE LINED NEW

2883
01:41:21,360 --> 01:41:22,800
ALIGNMENT AND SEGMENTATION

2884
01:41:22,800 --> 01:41:25,200
PIPELINE TO IMPROVE HOW NEURONS

2885
01:41:25,200 --> 01:41:26,440
COULD BE RECONSTRUCTED BY

2886
01:41:26,440 --> 01:41:27,480
ARTIFICIAL INTELLIGENCE AND RAN

2887
01:41:27,480 --> 01:41:29,240
THIS ON THE WHOLE BRAIN.

2888
01:41:29,240 --> 01:41:32,440
THE AI DETECTS SEGMENTS THAT ARE

2889
01:41:32,440 --> 01:41:35,360
OFTEN RECOGNIZABLE AS NOO

2890
01:41:35,360 --> 01:41:36,560
NEURONS, FOR EXAMPLE THESE GIANT

2891
01:41:36,560 --> 01:41:39,080
FIBER NEURONS INVOLVED IN HE

2892
01:41:39,080 --> 01:41:40,720
INVOLVED IN ESCAPE CIRCUITED

2893
01:41:40,720 --> 01:41:42,720
COMPARED TO ONES FROM PRINCETON

2894
01:41:42,720 --> 01:41:46,440
AI TO LIGHT MICROSCOPYING

2895
01:41:46,440 --> 01:41:48,080
STAINING IN THE LITERATURE AND

2896
01:41:48,080 --> 01:41:49,400
NEURON INVOLVED IN MEMORY.

2897
01:41:49,400 --> 01:41:51,760
THE AI IS VERY GOOD BUT NOT

2898
01:41:51,760 --> 01:41:53,360
PERFECT, MAKING ERRORS THAT

2899
01:41:53,360 --> 01:41:55,200
REQUIRE HUMAN PROOFREADING.

2900
01:41:55,200 --> 01:41:57,240
HERE IS A NEURON THAT GOT BROKEN

2901
01:41:57,240 --> 01:42:01,440
BECAUSE OF A MERGER WITH A --

2902
01:42:01,440 --> 01:42:01,840
CELL.

2903
01:42:01,840 --> 01:42:04,720
HERE ARE TWO NEURONS

2904
01:42:04,720 --> 01:42:09,440
ACCIDENTALLY MERGED, ONE

2905
01:42:09,440 --> 01:42:12,040
INVAGINATED INTO INTO ANOTHER.

2906
01:42:12,040 --> 01:42:14,360
HERE IS ONE THAT GOT BROKEN OFF

2907
01:42:14,360 --> 01:42:16,520
FROM WHERE IT LEFT OFF A LARGER

2908
01:42:16,520 --> 01:42:18,400
BACKBONE, HERE ARE A BUNCH OF

2909
01:42:18,400 --> 01:42:19,840
TWIGS, VERY FINE LITTLE

2910
01:42:19,840 --> 01:42:21,160
PROCESSES AT THE ENDS OF

2911
01:42:21,160 --> 01:42:23,440
DENDRITES THAT GOT ORPHANED OR

2912
01:42:23,440 --> 01:42:25,720
BROKE BROKEN OFF THE END, THAT

2913
01:42:25,720 --> 01:42:27,160
ACTUALLY HAPPENS WITH SOME

2914
01:42:27,160 --> 01:42:27,720
FREQUENCY.

2915
01:42:27,720 --> 01:42:31,640
BUT WE FIND THAT PROOFREADING

2916
01:42:31,640 --> 01:42:33,920
ORPHANED TWIGS SNTD CRITICAL --

2917
01:42:33,920 --> 01:42:37,480
IS NOT CRITICAL BECAUSE ANY TWO

2918
01:42:37,480 --> 01:42:40,840
CONNECTED NEURONS TEND TO BE

2919
01:42:40,840 --> 01:42:41,280
REDUNDANTLY CONNECTED.

2920
01:42:41,280 --> 01:42:42,200
SO EVEN IF SOME TWIGS ARE

2921
01:42:42,200 --> 01:42:43,680
MISSIONING, IT DOESN'T SEEM TO

2922
01:42:43,680 --> 01:42:47,000
AFFECT THE WIRING DIAGRAM.

2923
01:42:47,000 --> 01:42:48,360
SO WE MAINLY JUST PROOFREAD

2924
01:42:48,360 --> 01:42:51,000
BACKBONES OR THE LARGER BRANCHES

2925
01:42:51,000 --> 01:43:01,480
OF NEURONS AND NOT THE FINE

2926
01:43:05,160 --> 01:43:05,560
TWIGS.

2927
01:43:05,560 --> 01:43:06,200
BUT EVERYTHING ELSE NEEDS HUMAN

2928
01:43:06,200 --> 01:43:06,520
INTERVENTION.

2929
01:43:06,520 --> 01:43:07,080
SO WE CREATED FLY WIRE AS AN

2930
01:43:07,080 --> 01:43:07,680
ONLINE PLATFORM TO CROWDSOURCE

2931
01:43:07,680 --> 01:43:08,320
THE PROOFREADING THIS THIS WHOLE

2932
01:43:08,320 --> 01:43:08,680
BRAIN DATASET.

2933
01:43:08,680 --> 01:43:12,680
ANY SIGN SCIENTIST CAN JOIN TO

2934
01:43:12,680 --> 01:43:13,320
HELP PROOFREADS READ INTERESTS,

2935
01:43:13,320 --> 01:43:15,280
USERS NEED TO PASS A

2936
01:43:15,280 --> 01:43:17,040
PROOFREADING TEST ON ENTER THE

2937
01:43:17,040 --> 01:43:17,280
COMMUNITY.

2938
01:43:17,280 --> 01:43:20,440
FLY WIRE'S USER INTERFACE IS

2939
01:43:20,440 --> 01:43:21,080
BAIS ODD GOOGLE'S NEURO GLANCER

2940
01:43:21,080 --> 01:43:23,000
WITH OUR OWN MODIFICATIONS.

2941
01:43:23,000 --> 01:43:24,800
BEHIND UI IS OUR SPATIALLY

2942
01:43:24,800 --> 01:43:27,720
CHUNKED SUPER GRAPH THAT ALLOWS

2943
01:43:27,720 --> 01:43:30,040
SIMULTANEOUS COLLABORATIVE

2944
01:43:30,040 --> 01:43:30,840
EDITING.

2945
01:43:30,840 --> 01:43:32,480
USESSERS AGREE TO OUR PRINCIPLES

2946
01:43:32,480 --> 01:43:36,960
OF OPENNESS, FAIRNESS,

2947
01:43:36,960 --> 01:43:39,520
COMMUNICATION AND MUTUAL

2948
01:43:39,520 --> 01:43:41,040
RESPECT, WHICH ENSURE THAT

2949
01:43:41,040 --> 01:43:42,640
PEOPLE RECEIVE CREDIT FOR THEIR

2950
01:43:42,640 --> 01:43:43,040
WORK.

2951
01:43:43,040 --> 01:43:45,320
THESE PRINCIPLES WERE DESIGNED

2952
01:43:45,320 --> 01:43:47,720
WITH INPUT FROM OUR ADVISORY

2953
01:43:47,720 --> 01:43:48,320
BOARD AND IT'S BEEN GRATIFYING

2954
01:43:48,320 --> 01:43:49,520
TO SEE THAT SCIENTISTS ARE

2955
01:43:49,520 --> 01:43:51,720
SHARING THEIR DATA VERY OPENLY

2956
01:43:51,720 --> 01:43:52,360
BECAUSE OF THIS CAREFUL SYSTEM

2957
01:43:52,360 --> 01:43:53,640
OF CREDIT.

2958
01:43:53,640 --> 01:43:55,520
I HAVE NOW TALKED TO HUNDREDS OF

2959
01:43:55,520 --> 01:43:57,320
MEMBERS OF THE FLY COMMUNITY AS

2960
01:43:57,320 --> 01:43:59,120
I ONBOARD THEM AND I'M HUMBLED

2961
01:43:59,120 --> 01:44:03,360
AND APLAITZED BY -- AMAZED BY

2962
01:44:03,360 --> 01:44:05,200
HOW CAN READY PEOPLE ARE FOR

2963
01:44:05,200 --> 01:44:06,040
OPEN SCIENCE.

2964
01:44:06,040 --> 01:44:08,600
WE HAVE FLY WIRE MEMBERS FROM

2965
01:44:08,600 --> 01:44:09,320
MANY INSTITUTIONS ALL AROUND THE

2966
01:44:09,320 --> 01:44:11,400
WORLD.

2967
01:44:11,400 --> 01:44:12,040
PROOFREADING NEURONS IN FLY WIRE

2968
01:44:12,040 --> 01:44:12,960
IS REALLY FUN AND KIND OF

2969
01:44:12,960 --> 01:44:14,240
ADDICTIVE LIKE A VIDEO GAME

2970
01:44:14,240 --> 01:44:16,640
BECAUSE OF THE 3D EXPERIENCE.

2971
01:44:16,640 --> 01:44:17,560
YOU JUST DROP POINTS ON OBJECTS

2972
01:44:17,560 --> 01:44:19,480
THAT YOU WANT TO SPLIT APART,

2973
01:44:19,480 --> 01:44:22,760
FOR EXAMPLE, HERE IS A NEURON,

2974
01:44:22,760 --> 01:44:25,080
THE TUBULAR THING, THAT GOT

2975
01:44:25,080 --> 01:44:26,600
ACCIDENTALLY MERGED BY THE AI

2976
01:44:26,600 --> 01:44:29,040
WITH A BUNCH OF GLIA WHICH KIND

2977
01:44:29,040 --> 01:44:31,320
OF LOOKS LIKE SEAWEED AND JAMES

2978
01:44:31,320 --> 01:44:34,600
IS DROPPING RED POINTS ALONG THE

2979
01:44:34,600 --> 01:44:35,360
NEURON AND BLUE POINTS ALONG THE

2980
01:44:35,360 --> 01:44:37,760
GLIA TO SPLIT THEM APART.

2981
01:44:37,760 --> 01:44:39,960
AND THIS SUCCESSFULLY CUT THOSE

2982
01:44:39,960 --> 01:44:42,600
TWO THINGS, THE OUTER IS VERY

2983
01:44:42,600 --> 01:44:44,200
SMART -- THE ALGORITHM IS VERY

2984
01:44:44,200 --> 01:44:45,520
SMART SO YOU CAN BE KIND OF

2985
01:44:45,520 --> 01:44:47,640
ROUGH WITH YOUR POINT PLACEMENT.

2986
01:44:47,640 --> 01:44:49,680
THEN ONCE JAMES HIDES THE GLIA

2987
01:44:49,680 --> 01:44:52,280
CELL YOU CAN SEE THIS CLEANED UP

2988
01:44:52,280 --> 01:44:53,440
NEURON.

2989
01:44:53,440 --> 01:44:55,240
MERGING BROKEN PIECES IS EVEN

2990
01:44:55,240 --> 01:44:57,440
EASIER THAN SPLITTING, SO IF A

2991
01:44:57,440 --> 01:44:59,400
CELL WAS MISSING PART OF ITSELF

2992
01:44:59,400 --> 01:45:01,720
ONCE YOU FIND THE CONTINUATION

2993
01:45:01,720 --> 01:45:05,160
IT JUST TAKES TWO CLICKS TO ADD

2994
01:45:05,160 --> 01:45:07,560
THAT PIECE.

2995
01:45:07,560 --> 01:45:08,600
PUTTING TOGETHER CIRCUITS

2996
01:45:08,600 --> 01:45:10,240
REQUIRES KNOWING WHERE SYNAPSES

2997
01:45:10,240 --> 01:45:13,360
ONTO ONE ANOTHER, SO WE IMPORTED

2998
01:45:13,360 --> 01:45:14,600
SYNAPSES AUTOMATICALLY DEFECTED

2999
01:45:14,600 --> 01:45:16,560
BY THE LAB AND THIS CELL'S

3000
01:45:16,560 --> 01:45:17,920
INPUTS ARE SHOWN IN BLUE AND

3001
01:45:17,920 --> 01:45:20,760
OUTPUTS ARE SHOWN IN GREEN.

3002
01:45:20,760 --> 01:45:22,520
WE MADE THE SYNAPSES VARIABLE

3003
01:45:22,520 --> 01:45:24,640
THROUGH A CONNECTIVITY APP.

3004
01:45:24,640 --> 01:45:26,320
HERE IS A CELL WHERE THE APP

3005
01:45:26,320 --> 01:45:29,240
SHOWS THAT A LARGE NUMBER OF ITS

3006
01:45:29,240 --> 01:45:34,560
OUTPUTS ARE IN THIS CYAN REGION

3007
01:45:34,560 --> 01:45:36,840
ABLP AND THE APP ALSO SHOWS WHAT

3008
01:45:36,840 --> 01:45:38,760
IS THE PROBABILITY OF PARTICULAR

3009
01:45:38,760 --> 01:45:42,640
NERVE TRANSMITTER PHENOTYPES FOR

3010
01:45:42,640 --> 01:45:44,360
PARTICULAR CELL SYNAPTIC

3011
01:45:44,360 --> 01:45:44,640
CONNECTIONS.

3012
01:45:44,640 --> 01:45:47,640
YOU CAN ALSO SEE IN THE APP

3013
01:45:47,640 --> 01:45:49,600
LISTS OF THE UPSTREAM AND

3014
01:45:49,600 --> 01:45:52,200
DOWNSTREAM SYNAPTIC PARTNERS OF

3015
01:45:52,200 --> 01:45:53,840
THE CELL.

3016
01:45:53,840 --> 01:45:56,080
FOR EACH CELL WNT FLY WIRE

3017
01:45:56,080 --> 01:45:57,520
INTERFACE, A LIGHT BULB MENU

3018
01:45:57,520 --> 01:45:59,400
TAKES YOU TO ALL THE INFORMATION

3019
01:45:59,400 --> 01:46:01,120
ASSOCIATED WITH IT, SUCH AS A

3020
01:46:01,120 --> 01:46:02,640
CHANGE LOG OF WHO ARE ALL THE

3021
01:46:02,640 --> 01:46:05,040
PEOPLE WHO MADE PROOFREADING

3022
01:46:05,040 --> 01:46:06,720
EDITS, WHO MARKED THE CELL AS

3023
01:46:06,720 --> 01:46:07,480
COMPLETE, ALL THE PEOPLE THAT

3024
01:46:07,480 --> 01:46:09,000
PUT IN ANY IDENTIFYING

3025
01:46:09,000 --> 01:46:11,360
INFORMATION AND THINGS LIKE

3026
01:46:11,360 --> 01:46:12,240
THAT.

3027
01:46:12,240 --> 01:46:13,680
HERE IS ONE EXAMPLE OF HOW MUCH

3028
01:46:13,680 --> 01:46:15,840
ONE USER PROJECT CAN ACCOMPLISH

3029
01:46:15,840 --> 01:46:18,760
IN FLY WIRE.

3030
01:46:18,760 --> 01:46:20,560
IN A LAB AT CAMBRIDGE, MARKED

3031
01:46:20,560 --> 01:46:21,720
ALL THE NEURONS TRAVELING

3032
01:46:21,720 --> 01:46:22,920
THROUGH THE NECK BETWEEN THE

3033
01:46:22,920 --> 01:46:26,360
FLY'S BRAIN AND VENTRAL NERVE

3034
01:46:26,360 --> 01:46:28,960
CORD, AND TO MARK BOTH

3035
01:46:28,960 --> 01:46:30,360
DESCENDING NEURONS COMING DOWN

3036
01:46:30,360 --> 01:46:31,920
FROM THE BRAIN AND ASCENDING

3037
01:46:31,920 --> 01:46:33,680
NEURONS GOING UP TO THE BRAIN

3038
01:46:33,680 --> 01:46:36,680
AND THEN DID A DETAILED STUDY OF

3039
01:46:36,680 --> 01:46:38,080
DESCENDING NEURONS WHERE SHE

3040
01:46:38,080 --> 01:46:39,080
IDENTIFIED PRESUMABLY ALL OF

3041
01:46:39,080 --> 01:46:41,720
THEM BECAUSE OF THIS DETAILED

3042
01:46:41,720 --> 01:46:43,480
NECK TRANSECTION, MORE THAN

3043
01:46:43,480 --> 01:46:44,560
1300, WHICH WAS MORE THAN

3044
01:46:44,560 --> 01:46:46,240
PREVIOUS ESTIMATES, AND NOW WITH

3045
01:46:46,240 --> 01:46:48,880
THE CARD LAB HAS BEEN ABLE TO

3046
01:46:48,880 --> 01:46:51,400
MATCH MANY OF THEM TO GAL FORD

3047
01:46:51,400 --> 01:46:54,680
DRIVER LINES TO BE ABLE TO

3048
01:46:54,680 --> 01:46:56,320
GENETICALLY MANIPULATE NEURONAL

3049
01:46:56,320 --> 01:46:57,520
ACTIVITY IN THE CELLS TO CARRY

3050
01:46:57,520 --> 01:46:58,880
THEIR ROLE IN BAIMPLE THE YOU'LL

3051
01:46:58,880 --> 01:47:03,000
ALSO HEAR FROM ANOTHER FLY WIRE

3052
01:47:03,000 --> 01:47:04,880
POWER USER STEPHANIE HAMPEL

3053
01:47:04,880 --> 01:47:06,840
COMING UP IN TODAY'SCISM POSE

3054
01:47:06,840 --> 01:47:07,400
YUMG.

3055
01:47:07,400 --> 01:47:10,840
PROOFREAD NG FLY WIRE IS FAST,

3056
01:47:10,840 --> 01:47:12,480
ALTHOUGH SOME DENSE NEURONS TAKE

3057
01:47:12,480 --> 01:47:15,640
A LONG TIME, MEAN BACKBONE

3058
01:47:15,640 --> 01:47:17,920
PROOFREADING TIME PER NEURON IS

3059
01:47:17,920 --> 01:47:19,200
ONLY ABOUT ELEVEN MINUTES.

3060
01:47:19,200 --> 01:47:20,880
HOW WOULD THAT SCAPE UP TO

3061
01:47:20,880 --> 01:47:23,440
PRODUCING A CONCTOME OF TLT BRA?

3062
01:47:23,440 --> 01:47:24,560
IT DEPENDS ON HOW MANY CELLS

3063
01:47:24,560 --> 01:47:25,400
THERE ARE.

3064
01:47:25,400 --> 01:47:28,720
RECENTLY WE'VE RELEASED A

3065
01:47:28,720 --> 01:47:31,800
NUCLEUS DETECTOR WHICH FINDS

3066
01:47:31,800 --> 01:47:32,880
ABOUT 150,000 NEURONS IN THE

3067
01:47:32,880 --> 01:47:34,080
BRAIN, REQUIRING MORE THAN

3068
01:47:34,080 --> 01:47:35,320
20,000 PERSON HOURS TO PROOFREAD

3069
01:47:35,320 --> 01:47:39,640
BUT LUCKILY WE'VE GOT A BIG AND

3070
01:47:39,640 --> 01:47:40,640
GROWING COMMUNITY.

3071
01:47:40,640 --> 01:47:42,360
THE NUMBER OF WEEKLY USERS IS

3072
01:47:42,360 --> 01:47:44,040
ALWAYS GROWING, NOW FROM MORE

3073
01:47:44,040 --> 01:47:47,360
THAN 70 LABS, SO EDITS PER DAY

3074
01:47:47,360 --> 01:47:48,840
HAVE BEEN ACCELERATING, EVERY

3075
01:47:48,840 --> 01:47:50,360
POINT HERE SAN EDIT AND WE'VE

3076
01:47:50,360 --> 01:47:53,760
NOW PASSED 1.3 MILLION MAINLY

3077
01:47:53,760 --> 01:47:55,520
FOCUSED ON SAR IF THE CENTRAL

3078
01:47:55,520 --> 01:47:58,680
BRAIN AND HAVE PROOFREAD

3079
01:47:58,680 --> 01:48:00,000
TOGETHER 55,000 NEURONS AND WE

3080
01:48:00,000 --> 01:48:01,640
EXPECT IT TO START GOING EVEN

3081
01:48:01,640 --> 01:48:03,480
FASTER SINCE WE'VE JUST OPENED

3082
01:48:03,480 --> 01:48:06,120
UP FLY WIRE TO THE TOP PLAYERS

3083
01:48:06,120 --> 01:48:08,640
FROM I-WIRE THE SUN LABS'

3084
01:48:08,640 --> 01:48:09,960
PREVIOUS SCIENCE GAME.

3085
01:48:09,960 --> 01:48:12,240
HERE ARE RECENT BLOG POSTS FOR

3086
01:48:12,240 --> 01:48:13,560
THE PLAYERS.

3087
01:48:13,560 --> 01:48:15,440
IT'S NOT YET OPEN TO THE GENERAL

3088
01:48:15,440 --> 01:48:16,840
GAMING PUBLIC UNTIL WE ADD MORE

3089
01:48:16,840 --> 01:48:18,680
QUALITY CONTROL FEATURES, BUT

3090
01:48:18,680 --> 01:48:19,960
THE CURRENT PLIERS WHO HAVE

3091
01:48:19,960 --> 01:48:22,680
MOVED OVER FROM I-WIRE HAVE

3092
01:48:22,680 --> 01:48:24,120
YEARS OF EXPERIENCE IN EM.

3093
01:48:24,120 --> 01:48:27,040
TO HELP ENGAGE THEM WE'VE ALSO

3094
01:48:27,040 --> 01:48:29,360
ADDED FEATURES LIKE USER CHATS

3095
01:48:29,360 --> 01:48:30,960
AND PARTNERING PLAYERS WITH

3096
01:48:30,960 --> 01:48:32,080
SCIENTISTS TO UNDERSTAND

3097
01:48:32,080 --> 01:48:32,320
BIOLOGY.

3098
01:48:32,320 --> 01:48:34,280
SO FAR, EALT EXPERT PLAYERS

3099
01:48:34,280 --> 01:48:35,120
ONBOARDED WHO HAVE COMPLETED

3100
01:48:35,120 --> 01:48:37,000
MORE THAN 700 CELLS IN THEIR

3101
01:48:37,000 --> 01:48:38,080
FIRST FEW WEEKS.

3102
01:48:38,080 --> 01:48:39,600
FOR SCIENTISTS WE'RE HAPPY TO

3103
01:48:39,600 --> 01:48:41,040
ANNOUNCE TODAY THAT WE'LL ALSO

3104
01:48:41,040 --> 01:48:43,120
BE ACCEPTING APPLICATIONS FOR A

3105
01:48:43,120 --> 01:48:44,240
PROOFREADING SERVICE SUPPORTED

3106
01:48:44,240 --> 01:48:45,760
BY A NEW BRAIN INITIATIVE

3107
01:48:45,760 --> 01:48:47,440
GRANTED FOR DISSEMINATION.

3108
01:48:47,440 --> 01:48:48,840
WE PARTICULARLY ENCOURAGE FLY

3109
01:48:48,840 --> 01:48:50,600
LABS WORKING IN THE OPTIC LOBE

3110
01:48:50,600 --> 01:48:51,280
TO APPLY.

3111
01:48:51,280 --> 01:48:53,320
THE SERVICE IS CURRENTLY FREE

3112
01:48:53,320 --> 01:48:55,320
BUT WE'LL ASSESS THE COMMUNITY'S

3113
01:48:55,320 --> 01:48:58,120
INTEREST IN ADDITIONAL FEE-BASED

3114
01:48:58,120 --> 01:48:58,440
SERVICES.

3115
01:48:58,440 --> 01:49:00,160
FOR PLANNING ON TWO MILESTONES

3116
01:49:00,160 --> 01:49:02,920
FOR A WHOLE BRAIN CONNECTOME,

3117
01:49:02,920 --> 01:49:04,560
FIRST BEING CENTRAL BRAIN WHICH

3118
01:49:04,560 --> 01:49:05,960
CONTAINS ABOUT 50,000 NEURONS

3119
01:49:05,960 --> 01:49:07,880
AND IS ON TRACK TO BE ROW LEASED

3120
01:49:07,880 --> 01:49:08,960
LATER THIS YEAR AND SECOND BEING

3121
01:49:08,960 --> 01:49:11,800
TO ADD IN THE OPTIC LOBES, ABOUT

3122
01:49:11,800 --> 01:49:14,560
60,000 ADDITIONAL NEURONS.

3123
01:49:14,560 --> 01:49:16,280
TO SUM UP, FLY WIRE IS A

3124
01:49:16,280 --> 01:49:18,040
RESOURCE FOR NEURON CONNECT

3125
01:49:18,040 --> 01:49:19,040
ACTIVITY, MORPHOLOGY AND A

3126
01:49:19,040 --> 01:49:21,760
GROWING NUMBER OF CELL TYPE

3127
01:49:21,760 --> 01:49:22,360
IDENTIFICATIONS.

3128
01:49:22,360 --> 01:49:23,440
IT DISIBTS PROOFREADING OF A

3129
01:49:23,440 --> 01:49:25,040
WHOLE BRAIN TO THE COMMUNITY,

3130
01:49:25,040 --> 01:49:27,480
IT'S A LIVING DATASET VARIABLE

3131
01:49:27,480 --> 01:49:29,440
WHILE PROOFREADING DISPNS IT'S

3132
01:49:29,440 --> 01:49:30,960
APPROACHING A PROOFREAD

3133
01:49:30,960 --> 01:49:32,280
RECONSTRUCTION OF CENTRAL BRAIN

3134
01:49:32,280 --> 01:49:35,360
WITH THE WHOLE BRAIN TO FOLLOW.

3135
01:49:35,360 --> 01:49:36,200
THANKS FOR LISTENING.

3136
01:49:36,200 --> 01:49:37,880
I WOULD LIKE TO ACKNOWLEDGE OUR

3137
01:49:37,880 --> 01:49:39,080
AMAZING COMMUNITY IS ALL THE

3138
01:49:39,080 --> 01:49:40,640
PEOPLE AT PRINCETON AND AROUND

3139
01:49:40,640 --> 01:49:42,960
THE WORLD WHO CONTRIBUTE.

3140
01:49:42,960 --> 01:49:46,200
CALLING OUT SPECIAL ATTENTION TO

3141
01:49:46,200 --> 01:49:49,000
SVEN, JEFFERS LAB AND BRAIN

3142
01:49:49,000 --> 01:49:49,280
INITIATIVE.

3143
01:49:49,280 --> 01:49:53,160
THANKS, VERY MUCH.

3144
01:49:53,160 --> 01:49:56,240
>> HELLO, I'M WEI-CHUNG
LEE,

3145
01:49:56,240 --> 01:49:57,600
BOSTON CHILDREN'S HOSPITAL AND

3146
01:49:57,600 --> 01:49:58,080
HARVARD MEDICAL SCHOOL.

3147
01:49:58,080 --> 01:49:59,600
I WOULD LIKE TO QUICKLY THANK

3148
01:49:59,600 --> 01:50:00,720
THE ORGANIZERS FOR THE

3149
01:50:00,720 --> 01:50:01,760
OPPORTUNITY TO SHARE SOME OF THE

3150
01:50:01,760 --> 01:50:03,920
RECENT WORK IN MY LAB, IN THIS

3151
01:50:03,920 --> 01:50:07,400
CASE SPEARHEADED BY A VERY

3152
01:50:07,400 --> 01:50:12,760
TALENTED POST-DOC, AARON KUAN.

3153
01:50:12,760 --> 01:50:14,520
SO FIRST I WOULD LIKE YOU TO

3154
01:50:14,520 --> 01:50:16,200
CONSIDER, SAY, A BIKE RIDE FROM

3155
01:50:16,200 --> 01:50:19,120
MY LAB AT HARVARD MEDICAL SCHOOL

3156
01:50:19,120 --> 01:50:21,560
TO MIT AND I KNOW THAT AS I'M

3157
01:50:21,560 --> 01:50:22,840
TRAVELING DOWN HUNGTD TON AVENUE

3158
01:50:22,840 --> 01:50:25,120
AFTER I PASS BY THE MUSEUM OF

3159
01:50:25,120 --> 01:50:27,320
FINE ARTS AT NORTHEASTERN

3160
01:50:27,320 --> 01:50:29,200
UNIVERSITY AND QDOBA I KNOW THAT

3161
01:50:29,200 --> 01:50:32,880
I NEED TO TAKE A LEFT TURN ONTO

3162
01:50:32,880 --> 01:50:35,440
MASS CHUS ET CETERA AVENUE, WHAT

3163
01:50:35,440 --> 01:50:36,400
WE'RE UNDERSTANDING --

3164
01:50:36,400 --> 01:50:38,280
MASSACHUSETTS AVENUE AND WHAT

3165
01:50:38,280 --> 01:50:39,920
WE'RE INTERESTING IN SNGD HOW

3166
01:50:39,920 --> 01:50:41,880
DOES THE BRAIN TRANSFORM SENSORY

3167
01:50:41,880 --> 01:50:43,080
INFORMATION INTO SERIES OF

3168
01:50:43,080 --> 01:50:44,560
BEHAVIORAL CHOICES SUCH AS

3169
01:50:44,560 --> 01:50:45,520
TURNING OR NAVIGATING.

3170
01:50:45,520 --> 01:50:49,680
WE TEAMED UP TOES CONSTITUTED

3171
01:50:49,680 --> 01:50:52,120
CAN I DECISION-MAKING PATHS,

3172
01:50:52,120 --> 01:50:52,440
NAVIGATIONAL.

3173
01:50:52,440 --> 01:50:54,640
IN THIS CASE WHAT YOU SEE IS A

3174
01:50:54,640 --> 01:50:55,600
MOUSE THAT'S BEEN TRAINED TO

3175
01:50:55,600 --> 01:50:58,880
NAVIGATE THROUGH A TEAM MAZE AND

3176
01:50:58,880 --> 01:51:02,280
VIRTUAL REALITY SO AT THE

3177
01:51:02,280 --> 01:51:05,200
BEGINNING OF THE -- ARE -- THE

3178
01:51:05,200 --> 01:51:07,040
TEAM MAZE, THERE IS A VISUAL CUE

3179
01:51:07,040 --> 01:51:13,200
THAT TELLS THE ANIMAL

3180
01:51:13,200 --> 01:51:18,720
SO IN THIS CASE, THIS IS

3181
01:51:18,720 --> 01:51:21,600
ELECTRON MIGHT BE SCOPE PI

3182
01:51:21,600 --> 01:51:23,720
DATASET, SPANS SIX CORTICAL

3183
01:51:23,720 --> 01:51:25,280
LAYERS FROM PA TO WHITE MATTER,

3184
01:51:25,280 --> 01:51:28,560
WE'VE DONE THIS USING A TAPE

3185
01:51:28,560 --> 01:51:33,200
BASED USING THREK TRANSITION

3186
01:51:33,200 --> 01:51:35,000
MICROSCOPY DEVELOPED, SO WE

3187
01:51:35,000 --> 01:51:37,840
FOCUS ON TRANSMISSION ELECTRON

3188
01:51:37,840 --> 01:51:43,880
MICROSCOPY BECAUSE # IT GIVES US

3189
01:51:43,880 --> 01:51:48,160
HIGHER SPATIAL WITH -- SIGNAL TO

3190
01:51:48,160 --> 01:51:48,520
NOISE.

3191
01:51:48,520 --> 01:51:51,320
WIDE FIELD IMAGING IS MODALITY

3192
01:51:51,320 --> 01:51:53,320
AND ULTIMATELY LESS EXPENSIVE IN

3193
01:51:53,320 --> 01:51:55,520
TERMS OF INSTRUMENTATION COSTS

3194
01:51:55,520 --> 01:51:58,920
COMPARED TO COMPETING SEM

3195
01:51:58,920 --> 01:52:04,560
METHODS CURRENTLY.

3196
01:52:04,560 --> 01:52:09,440
WHAT THE LAB THEN DID WAS TO

3197
01:52:09,440 --> 01:52:11,480
CORRESPOND THESE WITH THE

3198
01:52:11,480 --> 01:52:13,560
CALCIUM IMAGING WITH THOSE IN

3199
01:52:13,560 --> 01:52:16,080
YEN, SO THE WAY WE DO THIS IS TO

3200
01:52:16,080 --> 01:52:17,480
ESSENTIALLY USE THE VASCULATURE

3201
01:52:17,480 --> 01:52:19,800
AS A ROAD MAP USING THE SURFACE

3202
01:52:19,800 --> 01:52:20,880
BLOOD VESSELS ON THE SURFACE OF

3203
01:52:20,880 --> 01:52:22,320
THE BRAIN AND ULTIMATELY GOING

3204
01:52:22,320 --> 01:52:25,200
TO FINER AND FINER BLOOD VESSELS

3205
01:52:25,200 --> 01:52:26,920
UNTIL WE HAVE MATCHING ONE FOR

3206
01:52:26,920 --> 01:52:29,760
ONE CELLS AND SUB BODIES BETWEEN

3207
01:52:29,760 --> 01:52:34,360
THE IN VIVO IMAGING AND

3208
01:52:34,360 --> 01:52:36,640
MICROSCOPESCOPY -- OR IN VIVO

3209
01:52:36,640 --> 01:52:39,840
IMAGING ELECTRON MIEPSCOPY

3210
01:52:39,840 --> 01:52:41,400
DATASET.

3211
01:52:41,400 --> 01:52:43,040
AND THEN SUBSEQUENTLY WHAT WE

3212
01:52:43,040 --> 01:52:44,640
CAN DO IS RECONSTRUCT THESE

3213
01:52:44,640 --> 01:52:48,680
CELLS IN THE EM AND ASK WHO

3214
01:52:48,680 --> 01:52:51,640
THEIR PRE AND POST SYNAPTIC

3215
01:52:51,640 --> 01:52:55,600
PARTNERS ARE.

3216
01:52:55,600 --> 01:52:57,600
SO WHAT I'M SHOWING YOU HERE,

3217
01:52:57,600 --> 01:52:58,960
HOPEFULLY YOU CAN SEE IT EVEN

3218
01:52:58,960 --> 01:53:02,240
DESPITE THE BGHTD BACKGROUND --

3219
01:53:02,240 --> 01:53:04,360
DESPITE THE BACKGROUND S A MOVIE

3220
01:53:04,360 --> 01:53:05,560
OF SOME OF THE CELL WE

3221
01:53:05,560 --> 01:53:07,960
RECONSTRUCTED IN EM, FOR CLARITY

3222
01:53:07,960 --> 01:53:09,600
I'VE OMITTED SOME OF THE

3223
01:53:09,600 --> 01:53:11,800
COLLATERAL AXONS IN THIS CASE,

3224
01:53:11,800 --> 01:53:15,400
THEY'RE RANDOMLY COLORED BUT

3225
01:53:15,400 --> 01:53:16,760
THEIR LUMINESCENCE IS BASED ON

3226
01:53:16,760 --> 01:53:19,080
THE ACTIVITY OF THOSE CELLS

3227
01:53:19,080 --> 01:53:19,920
MEASURED IN VIVO.

3228
01:53:19,920 --> 01:53:21,200
WHAT YOU SEE ON THE BOTTOM

3229
01:53:21,200 --> 01:53:22,400
LEFT-HAND CORNER IS WHAT THE

3230
01:53:22,400 --> 01:53:24,040
MOUSE IS ACTUALLY SEEING IN

3231
01:53:24,040 --> 01:53:26,000
VIRTUAL REALITY AS IT WAS

3232
01:53:26,000 --> 01:53:26,960
NAVIGATING THROUGH THIS TEAM

3233
01:53:26,960 --> 01:53:27,280
MAZE.

3234
01:53:27,280 --> 01:53:29,080
SO WHAT WE HAVE HERE IS THAT

3235
01:53:29,080 --> 01:53:32,680
WE'RE BRINGING TOGETHER

3236
01:53:32,680 --> 01:53:34,080
BASICALLY BEHAVIOR FUNCTIONAL

3237
01:53:34,080 --> 01:53:36,920
IMAGING AND ULTIMATELY SYNAPTIC

3238
01:53:36,920 --> 01:53:38,040
CONNECTIVITY BRIDGING THESE

3239
01:53:38,040 --> 01:53:40,120
THREE LEVELS TO TRY TO

3240
01:53:40,120 --> 01:53:42,400
UNDERSTAND HOW NEURAL CIRCUITS

3241
01:53:42,400 --> 01:53:50,480
UNDERLIE FUNCTION AND BEHAVIOR.

3242
01:53:50,480 --> 01:53:52,120
SO WHAT DID WE FIND?

3243
01:53:52,120 --> 01:53:53,920
FIRST THING WE DID WAS TO LOOK

3244
01:53:53,920 --> 01:53:59,240
AT INHIBITORY ASSOCIATION AREA

3245
01:53:59,240 --> 01:54:01,440
AND FOUND ESSENTIALLY AS CHOICE

3246
01:54:01,440 --> 01:54:02,600
SELECTIVE AS EXCITATORY ONES AND

3247
01:54:02,600 --> 01:54:05,160
THIS IS IN CONTRAST TO SOME

3248
01:54:05,160 --> 01:54:07,800
PRIMARY SENSORY AREAS WHERE

3249
01:54:07,800 --> 01:54:09,200
INTERNEURONS APPEAR TO BE MORE

3250
01:54:09,200 --> 01:54:10,120
BROADLY.

3251
01:54:10,120 --> 01:54:11,960
NOW, THIS CHOICE SELECTIVITY

3252
01:54:11,960 --> 01:54:14,560
SUGGESTS THEY MAY BE SOMEHOW

3253
01:54:14,560 --> 01:54:16,080
IMPORTANT IN COMPUTATIONS THAT

3254
01:54:16,080 --> 01:54:22,920
THIS CIRCUIT IS PERFORMING.

3255
01:54:22,920 --> 01:54:25,720
THIS IS ALSO CONSISTENT WITH

3256
01:54:25,720 --> 01:54:28,920
RECENT DATA FROM ANN CHURCHLIN'S

3257
01:54:28,920 --> 01:54:31,680
LAB WHERE THEY ALSO FIND

3258
01:54:31,680 --> 01:54:33,720
INHIBITORY NEURONS THAT APPEAR

3259
01:54:33,720 --> 01:54:36,040
TO BE CHOICE SELECTIVE.

3260
01:54:36,040 --> 01:54:37,440
THIS IS HOWEVER IN CONTRAST TO

3261
01:54:37,440 --> 01:54:39,720
KIND OF MOST NETWORK MODELS THAT

3262
01:54:39,720 --> 01:54:42,240
IF I DRAW YOUR ATTENTION ON THE

3263
01:54:42,240 --> 01:54:45,000
LEFT DIAGRAM SUGGEST THAT MOST

3264
01:54:45,000 --> 01:54:48,320
INHIBITION IS KIND OF THIS BROAD

3265
01:54:48,320 --> 01:54:49,200
NONSELECTIVE INHIBITION.

3266
01:54:49,200 --> 01:54:50,360
SO THEN THE QUESTION BECOMES

3267
01:54:50,360 --> 01:54:53,120
LIKE HOW IS THIS INHIBITION THE

3268
01:54:53,120 --> 01:54:54,400
SELECTIVE INHIBITION, HOW IS

3269
01:54:54,400 --> 01:54:56,440
THAT WIRED INTO THE CIRCUIT AND

3270
01:54:56,440 --> 01:54:58,600
WHAT KIND OF COMPUTATIONS COULD

3271
01:54:58,600 --> 01:54:59,480
IT UNDERLIE?

3272
01:54:59,480 --> 01:55:01,320
FOR EXAMPLE, IN THE MIDDLE

3273
01:55:01,320 --> 01:55:03,400
DIAGRAM YOU HAVE KIND OF

3274
01:55:03,400 --> 01:55:04,800
INHIBITORY SELECTIVE CELLS THAT

3275
01:55:04,800 --> 01:55:06,880
MAY BE INHIBITING TOES

3276
01:55:06,880 --> 01:55:08,000
EXCITATORY CELLS FROM WHICH

3277
01:55:08,000 --> 01:55:09,840
THEY'RE GETTING THEIR

3278
01:55:09,840 --> 01:55:10,760
EXCITATION, WHEREAS THE

3279
01:55:10,760 --> 01:55:11,920
RIGHT-HAND SIDE, YOU SAY ANOTHER

3280
01:55:11,920 --> 01:55:13,920
EXAMPLE OF CONNECTIVITY WHERE

3281
01:55:13,920 --> 01:55:17,080
INHIBITION IS ESSENTIAL

3282
01:55:17,080 --> 01:55:18,280
CROSS-INHIBITION WHERE

3283
01:55:18,280 --> 01:55:21,440
EXCITATORY CELLS ARE INHIBITED

3284
01:55:21,440 --> 01:55:23,080
BY INHIBITORY CELLS THAT ARE

3285
01:55:23,080 --> 01:55:25,280
SELECTED FOR THE OPPOSING

3286
01:55:25,280 --> 01:55:25,760
CHOICE.

3287
01:55:25,760 --> 01:55:26,640
ULTIMATELY THIS IS WHAT I'M

3288
01:55:26,640 --> 01:55:32,760
GOING TO SHOW YOU WE FIND IN OUR

3289
01:55:32,760 --> 01:55:33,040
DATA.

3290
01:55:33,040 --> 01:55:36,120
SO FIRST LET'S LOOK AT THE

3291
01:55:36,120 --> 01:55:37,240
FUNCTIONALLY SELECTIVE

3292
01:55:37,240 --> 01:55:38,880
CONNECTIVITY BETWEEN EXCITATORY

3293
01:55:38,880 --> 01:55:40,200
TO INHIBITORY CELLS.

3294
01:55:40,200 --> 01:55:41,480
SO IF YOU HAVE EXCITATORY CELLS

3295
01:55:41,480 --> 01:55:43,920
THE TOP, ONE POSSIBILITY IS THAT

3296
01:55:43,920 --> 01:55:45,760
EXCITATORY CELLS MAKE MORE

3297
01:55:45,760 --> 01:55:48,080
CONNECTIONS THAN INHIBITORY

3298
01:55:48,080 --> 01:55:53,200
CELLS OF SIMILAR ARE SELECTIVITY

3299
01:55:53,200 --> 01:55:54,120
WHEREAS YOU COULD HAVE

3300
01:55:54,120 --> 01:55:55,280
EXCITATORY CELLS MAKING MORE

3301
01:55:55,280 --> 01:55:57,280
CONNECTIONS ONTO INHIBITORY

3302
01:55:57,280 --> 01:55:58,360
CELLS OF THE OPPOSITE

3303
01:55:58,360 --> 01:55:58,800
SELECTIVITY.

3304
01:55:58,800 --> 01:56:03,440
SO WHAT WE FIND IS THAT IF WE

3305
01:56:03,440 --> 01:56:08,000
LOOK AT ANTI-SELECTIVE VERSUS

3306
01:56:08,000 --> 01:56:10,080
CO-SIMILAR, EXCITATORY TO

3307
01:56:10,080 --> 01:56:11,200
INHIBITORY CONNECTIONS, THE

3308
01:56:11,200 --> 01:56:13,080
EXCITATORY TO INHIBITORY

3309
01:56:13,080 --> 01:56:15,360
CONNECTIVITY IS SUCH THAT IT'S

3310
01:56:15,360 --> 01:56:16,880
BIASED TOWARDS CONNECTIONS FROM

3311
01:56:16,880 --> 01:56:19,400
EXCITATORY CELLS ONTO CO-TUNED

3312
01:56:19,400 --> 01:56:21,560
OR SIMILARLY SELECTED INHIBITORY

3313
01:56:21,560 --> 01:56:24,880
CELLS AND WE CAN PLOT THIS IN A

3314
01:56:24,880 --> 01:56:26,600
CONTINUOUS MANNER AND WHAT WE

3315
01:56:26,600 --> 01:56:28,160
SEE IS THIS POSITIVE CORRELATION

3316
01:56:28,160 --> 01:56:30,440
BETWEEN THE PROCEED AND POST

3317
01:56:30,440 --> 01:56:33,400
CELL SIMILARITY AND THE NUMBER

3318
01:56:33,400 --> 01:56:36,240
OF DENSITY OF CONNECTIONS THAT

3319
01:56:36,240 --> 01:56:43,400
THEY RECEIVE.

3320
01:56:43,400 --> 01:56:46,520
SO WILL ULTIMATELY WE SEE THAT E

3321
01:56:46,520 --> 01:56:48,840
TO I CONNECTIVITY IS

3322
01:56:48,840 --> 01:56:50,360
CO-SELECTIVE F WE LOOK AT THE

3323
01:56:50,360 --> 01:56:52,120
INHIBITORY TO EXCITATORY

3324
01:56:52,120 --> 01:56:53,440
CONNECTIONS, WE ACTUALLY SEE THE

3325
01:56:53,440 --> 01:56:53,720
OPPOSITE.

3326
01:56:53,720 --> 01:56:56,360
P SO WHAT WE SEE IS THAT

3327
01:56:56,360 --> 01:56:58,720
INHIBITORY CELLS ACTUALLY

3328
01:56:58,720 --> 01:57:01,120
PROVIDE MORE SYNAPSIS ONTO

3329
01:57:01,120 --> 01:57:03,480
EXCITATORY CELLS OF THE OPPOSING

3330
01:57:03,480 --> 01:57:03,920
SELECTIVITY.

3331
01:57:03,920 --> 01:57:05,360
AND THEREFORE WE SEE THIS KIND

3332
01:57:05,360 --> 01:57:09,400
OF NEGATIVE CORRELATION WHEN YOU

3333
01:57:09,400 --> 01:57:13,120
LOOK AT THE RELATIONSHIP BETWEEN

3334
01:57:13,120 --> 01:57:16,640
SYNAPSE NUMBER OR SYNAPSE

3335
01:57:16,640 --> 01:57:20,280
DENSITY TO SIMILARITY OF

3336
01:57:20,280 --> 01:57:23,240
SELECTIVITY.

3337
01:57:23,240 --> 01:57:26,320
SO WHAT WE SEE IS THAT

3338
01:57:26,320 --> 01:57:28,800
INHIBITORY TO EXCITATORY

3339
01:57:28,800 --> 01:57:29,160
ANTI-SELECTIVE.

3340
01:57:29,160 --> 01:57:31,760
SO WHAT WE FIND IS THIS

3341
01:57:31,760 --> 01:57:34,280
INHIBITORY, THIS OPPONENT

3342
01:57:34,280 --> 01:57:38,320
INHIBITORY ACTIVITY MOTIF WHERE

3343
01:57:38,320 --> 01:57:41,040
TO THE FIRST ORDER INHIBITOR

3344
01:57:41,040 --> 01:57:43,600
INHIBITION IS SUPPRESSING THE

3345
01:57:43,600 --> 01:57:46,520
OPPOSING CHOICE IN TERMS OF

3346
01:57:46,520 --> 01:57:47,640
EXPRESSING EXCITATORY CELLS WITH

3347
01:57:47,640 --> 01:57:49,280
THE OPPOSING CHOICE BUT YOU HAVE

3348
01:57:49,280 --> 01:57:50,600
THIS HIGHER ORDER OF ACTION

3349
01:57:50,600 --> 01:57:52,440
WHERE IF YOU FOR EXAMPLE HAVE A

3350
01:57:52,440 --> 01:57:55,080
LEFT SELECTIVE TURN SIGNAL,

3351
01:57:55,080 --> 01:57:57,920
BECAUSE THERE IS INCREASED

3352
01:57:57,920 --> 01:58:00,200
INHIBITION ONTO THE LEFT

3353
01:58:00,200 --> 01:58:01,640
SELECTIVE INHIBITORY CELLS THAT

3354
01:58:01,640 --> 01:58:03,720
ARE SUPPRESSING THE RIGHT

3355
01:58:03,720 --> 01:58:05,160
SELECTIVE INHIBITORY CELLS OR

3356
01:58:05,160 --> 01:58:06,560
EXCITATORY CELLS, THAT CAUSES

3357
01:58:06,560 --> 01:58:09,200
LESS INHIBITION BACK ONTO THE

3358
01:58:09,200 --> 01:58:11,480
LEFT SELECTED EXCITATORY CELLS.

3359
01:58:11,480 --> 01:58:14,000
SO WE BELIEVE THAT THIS HELPS TO

3360
01:58:14,000 --> 01:58:15,960
SEPARATE KIND OF THE POPULATION

3361
01:58:15,960 --> 01:58:17,920
DYNAMICS IN THE CIRCUIT AND BIAS

3362
01:58:17,920 --> 01:58:19,880
THE CHOICE OF THE ANIMAL TOWARDS

3363
01:58:19,880 --> 01:58:22,200
ONE SIDE OR THE OTHER AS THEY

3364
01:58:22,200 --> 01:58:26,360
KIND OF NAVIGATE THROUGH THIS.

3365
01:58:26,360 --> 01:58:27,680
SO IN THE INTEREST OF TIME, I'M

3366
01:58:27,680 --> 01:58:29,840
GOING TO JUST QUICKLY TALK ABOUT

3367
01:58:29,840 --> 01:58:35,200
CIRCUIT MODELING, TOGETHER WITH

3368
01:58:35,200 --> 01:58:38,360
STEFANO AND J CU LIO WHAT THEY

3369
01:58:38,360 --> 01:58:39,920
DID WAS DEVELOP AND TRAIN AN

3370
01:58:39,920 --> 01:58:41,360
ARTIFICIAL RECURRENT NEURAL

3371
01:58:41,360 --> 01:58:42,200
NETWORK WITH THE SAME NUMBER OF

3372
01:58:42,200 --> 01:58:45,280
CELLS THAT WE RECORDED IN VIVO

3373
01:58:45,280 --> 01:58:47,800
BUT THEY WERE KIND OF THEIR

3374
01:58:47,800 --> 01:58:49,240
CONNECTIVITY RATES WERE

3375
01:58:49,240 --> 01:58:50,640
INITIALLY RANDOMIZED BUT THEN

3376
01:58:50,640 --> 01:58:52,840
TRAINED THE WHOLE ENTIRE

3377
01:58:52,840 --> 01:58:53,640
ARTIFICIAL NEURAL NETWORK WAS

3378
01:58:53,640 --> 01:58:56,480
TRAIBLED ON RECA PILT LATE --

3379
01:58:56,480 --> 01:58:59,280
TRAINED TO RECAPITULATE THE

3380
01:58:59,280 --> 01:59:02,880
ACTIVITY RATE IN VIVO AND WE SEE

3381
01:59:02,880 --> 01:59:05,440
WE RECAPITULATE THIS COMPONENT

3382
01:59:05,440 --> 01:59:06,840
INHIBITORY MOW MOTIF WHERE YOU

3383
01:59:06,840 --> 01:59:09,040
HAVE EXCITATORY TO INHIBITORY

3384
01:59:09,040 --> 01:59:10,160
CONNECTIVITY THAT IS

3385
01:59:10,160 --> 01:59:12,120
CO-SELECTIVE AND INHIBITORY TO

3386
01:59:12,120 --> 01:59:13,680
EXCITATORY CONNECTIVITY THAT IS

3387
01:59:13,680 --> 01:59:14,760
ANTI-SELECTIVE SO WE THINK THAT

3388
01:59:14,760 --> 01:59:16,800
THIS IS KIND OF A GENERAL

3389
01:59:16,800 --> 01:59:19,280
PRINCIPLE OF NEURAL NETWORKS

3390
01:59:19,280 --> 01:59:21,600
THAT ARE INVOLVED IN THINGS LIKE

3391
01:59:21,600 --> 01:59:25,000
OR TASKS LIKE DECISION-MAKING.

3392
01:59:25,000 --> 01:59:26,720
SO IN THE INTEREST OF TIME, I'M

3393
01:59:26,720 --> 01:59:29,880
GOING TO END HERE BUT BASICALLY

3394
01:59:29,880 --> 01:59:31,800
THIS IS TELLING US THAT OR IT

3395
01:59:31,800 --> 01:59:34,480
SUGGESTS THAT DIFFERENT CORTICAL

3396
01:59:34,480 --> 01:59:36,920
AREAS ARE ESSENTIALLY MAY HAVE

3397
01:59:36,920 --> 01:59:38,600
DIFFERENT CONNECTIVITY ROLES

3398
01:59:38,600 --> 01:59:40,440
THAT IT COULD PERFORM AND

3399
01:59:40,440 --> 01:59:41,320
UNDERLIE DIFFERENT FUNCTIONS

3400
01:59:41,320 --> 01:59:42,960
WHERE YOU HAVE SELECTIVE

3401
01:59:42,960 --> 01:59:45,560
CONNECTIVITY OF INHIBITORY CELLS

3402
01:59:45,560 --> 01:59:47,320
IN THE PARIETAL CORTEX COMPARED

3403
01:59:47,320 --> 01:59:49,960
TO BROADLY ATTUNED MORE RANDOM

3404
01:59:49,960 --> 01:59:51,600
CONNECTIVITY IN PRIMARY SENSORY

3405
01:59:51,600 --> 01:59:57,200
AREAS WHICH MAY BE BETTER SUITED

3406
01:59:57,200 --> 01:59:58,280
FOR GAME CONTROL AND FINALLY I

3407
01:59:58,280 --> 01:59:59,600
WOULD LIKE TO THANK THE PEOPLE

3408
01:59:59,600 --> 02:00:00,880
IN MY LAB THAT PERFORMED AND

3409
02:00:00,880 --> 02:00:02,440
HELPED WITH THIS STUDY AS WELL

3410
02:00:02,440 --> 02:00:03,840
AS THE FUNDING AND SUPPORT THAT

3411
02:00:03,840 --> 02:00:04,680
WE'VE RECEIVED.

3412
02:00:04,680 --> 02:00:08,520
SO THANK YOU.

3413
02:00:08,520 --> 02:00:10,320
>> THE ABILITY TO PRODUCE

3414
02:00:10,320 --> 02:00:12,480
COMPLEX BEHAVIORS BY ASSEMBLING

3415
02:00:12,480 --> 02:00:14,240
SEQUENCES OF DIFFERENT MOVEMENTS

3416
02:00:14,240 --> 02:00:16,960
IS ESSENTIAL FOR PURPOSEFUL

3417
02:00:16,960 --> 02:00:17,960
BEHAVIOR AND SURVIVAL.

3418
02:00:17,960 --> 02:00:20,360
OUR LAB IS INTERESTED IN HOW

3419
02:00:20,360 --> 02:00:21,680
MOVEMENT SEQUENCES ARE GENERATED

3420
02:00:21,680 --> 02:00:26,720
BY THE NERVOUS SYSTEM.

3421
02:00:26,720 --> 02:00:28,800
WE STUDIED GROWING BEHAVIOR IN

3422
02:00:28,800 --> 02:00:30,440
FRUIT FLIES AS MODEL TO

3423
02:00:30,440 --> 02:00:32,040
UNDERSTAND HOW SUCH SEQUENCES

3424
02:00:32,040 --> 02:00:36,000
ARE PRODUCED, AND YOU MIGHT

3425
02:00:36,000 --> 02:00:38,000
WONDER WHY GROWING BEHAVIOR,

3426
02:00:38,000 --> 02:00:39,720
BECAUSE THE CONSIST OF THE

3427
02:00:39,720 --> 02:00:40,720
STEREOTYPE SEQUENCE OF MOVE

3428
02:00:40,720 --> 02:00:42,360
MGHTS THAT RULE THE DIFFERENT

3429
02:00:42,360 --> 02:00:43,040
BODY TYPES.

3430
02:00:43,040 --> 02:00:46,320
SO WE USED GROOMING AND FRUIT

3431
02:00:46,320 --> 02:00:48,520
FLIES OR FRUIT FLIES

3432
02:00:48,520 --> 02:00:49,160
SPECIFICALLY BECAUSE OF THE

3433
02:00:49,160 --> 02:00:50,920
TOOLS THAT ENABLE US TO IDENTIFY

3434
02:00:50,920 --> 02:00:53,800
AND MAP NEURAL CIRCUITS RS AND

3435
02:00:53,800 --> 02:00:55,480
THE SYNAPTIC RESOLUTION.

3436
02:00:55,480 --> 02:00:57,600
ONE WAY WE CAN EASILY ELICIT

3437
02:00:57,600 --> 02:00:58,800
GROWING BEHAVIOR IN THE LAB IS

3438
02:00:58,800 --> 02:01:02,640
BY CODING FLIES AND WHAT THIS

3439
02:01:02,640 --> 02:01:05,400
DOES IS CAUSES THE FLY TO MOVE

3440
02:01:05,400 --> 02:01:08,440
TO CLEAN ITS WHOLE BODY USING

3441
02:01:08,440 --> 02:01:09,760
DISTINCT GROOMING MOVEMENTS.

3442
02:01:09,760 --> 02:01:11,680
LET ME SHOW YOU WHAT I MEAN BY

3443
02:01:11,680 --> 02:01:12,120
THIS.

3444
02:01:12,120 --> 02:01:13,960
P IN THE VIDEO ON THE LEFT, YOU

3445
02:01:13,960 --> 02:01:16,880
CAN SEE A FLY A DIRTY FLY USES

3446
02:01:16,880 --> 02:01:18,800
FRONT LEGS TO GROOM ITS HEAD.

3447
02:01:18,800 --> 02:01:20,920
BUT WE FOUND THAT THE FLY CAN

3448
02:01:20,920 --> 02:01:22,560
ACTUALLY GROOM SPECIFIC PARTS OF

3449
02:01:22,560 --> 02:01:25,960
THE HEAD SUCH AS ONLY ITS EYES

3450
02:01:25,960 --> 02:01:27,720
OR ANTENNA OR MOUTHPARTS.

3451
02:01:27,720 --> 02:01:29,440
AND ON THE RIGHT YOU CAN SEE A

3452
02:01:29,440 --> 02:01:32,520
DIRTY FLY USING ITS HIND LEGS

3453
02:01:32,520 --> 02:01:34,600
USING ITS POSTERIOR BODY AND AT

3454
02:01:34,600 --> 02:01:36,160
THE MOMENT IT'S GROOMING ITS

3455
02:01:36,160 --> 02:01:37,440
ABDOMEN AND IT'S SWITCHING RIGHT

3456
02:01:37,440 --> 02:01:39,560
NOW TO ITS SWINGS.

3457
02:01:39,560 --> 02:01:41,720
SO IN OUR PREVIOUS WORK, WE

3458
02:01:41,720 --> 02:01:44,520
FOUND THAT FLIES GROOM IN AN

3459
02:01:44,520 --> 02:01:46,680
ANTERIOR TO POSTERIOR GROOMING

3460
02:01:46,680 --> 02:01:49,840
SEQUENCE THAT STARTS WITH THE

3461
02:01:49,840 --> 02:01:52,880
EYES, PROCEEDS TO THEIR ANTENNA,

3462
02:01:52,880 --> 02:01:59,120
MOUTHPARTS, ABDOMEN, WINGS, AND

3463
02:01:59,120 --> 02:02:00,120
WE ALSO PREVIOUSLY DISCOVERED

3464
02:02:00,120 --> 02:02:01,520
THAT THE GROOMING SEQUENCE IS

3465
02:02:01,520 --> 02:02:04,800
PRODUCE BID A PARALLEL MODEL OF

3466
02:02:04,800 --> 02:02:05,520
HIERARCHICAL SUPPRESSION WHICH

3467
02:02:05,520 --> 02:02:07,000
YOU CAN SEE HERE.

3468
02:02:07,000 --> 02:02:08,600
I'M NOT GOING TO GO INTO MUCH

3469
02:02:08,600 --> 02:02:10,400
DETAIL OF THIS MODEL BUT I

3470
02:02:10,400 --> 02:02:13,120
DOMENT TO POINT OUT A COUPLE OF

3471
02:02:13,120 --> 02:02:14,240
FEATURE -- BUT I DO WANT TO

3472
02:02:14,240 --> 02:02:16,680
POINT OUT A COUPLE OF FEATURES

3473
02:02:16,680 --> 02:02:17,760
THAT ARE IMPORTANT TO UNDERSTAND

3474
02:02:17,760 --> 02:02:19,200
FOR TODAY'S PART.

3475
02:02:19,200 --> 02:02:20,840
WHEN WE DUST THE PARTICULAR BODY

3476
02:02:20,840 --> 02:02:23,480
PART SUCH AS THE 5BD, ONLY THAT

3477
02:02:23,480 --> 02:02:24,880
MOVEMENT GETS ACTIVATED.

3478
02:02:24,880 --> 02:02:28,720
HOWEVER, WHEN FLIES ARE --

3479
02:02:28,720 --> 02:02:31,600
DIFFERENT MUTE OOL DIFFERENT

3480
02:02:31,600 --> 02:02:32,360
MUTUALLY EXCLUSIVE BODY

3481
02:02:32,360 --> 02:02:33,240
MOVEMENTS THAT CLEAN DIFFERENT

3482
02:02:33,240 --> 02:02:35,320
PARTS OF THE HEAD OR BODY

3483
02:02:35,320 --> 02:02:37,480
ACTIVATED IN PARALLEL BY

3484
02:02:37,480 --> 02:02:39,040
MECHANIC AN NOTICE SENSORY

3485
02:02:39,040 --> 02:02:40,800
NEURONS THAT DETECT DUST ON THAT

3486
02:02:40,800 --> 02:02:41,320
BODY PART.

3487
02:02:41,320 --> 02:02:43,200
SO THE NEED TO PERFORM ALL OF

3488
02:02:43,200 --> 02:02:45,400
THESE DIFFERENT MOVEMENTS MEANS

3489
02:02:45,400 --> 02:02:47,440
THAT THEY ARE ALL COMPETING FOR

3490
02:02:47,440 --> 02:02:49,120
OUTPUT, BUT ONLY ONE MOVEMENT

3491
02:02:49,120 --> 02:02:50,960
CAN BE PERFORMED AT A TIME.

3492
02:02:50,960 --> 02:02:54,120
SO THIS GETS RESULTS THROUGH

3493
02:02:54,120 --> 02:02:56,800
HIERARCHICAL SUPPRESSION WHEREBY

3494
02:02:56,800 --> 02:02:59,920
EARLIER MOVEMENTS SUPPRESSION

3495
02:02:59,920 --> 02:03:03,080
LATER ONES.

3496
02:03:03,080 --> 02:03:04,600
THIS SO-CALLED PARALLEL SMODLE

3497
02:03:04,600 --> 02:03:08,640
OF GENERAL INTEREST ACTUALLY

3498
02:03:08,640 --> 02:03:10,920
BECAUSE SIMILAR MODELINGS HAVE

3499
02:03:10,920 --> 02:03:12,600
BEEN USED TO DESCRIBE HOW

3500
02:03:12,600 --> 02:03:13,760
DIFFERENT BEHAVIOR SEQUENCE RS

3501
02:03:13,760 --> 02:03:15,600
PRODUCE AND HAD THIS MODEL

3502
02:03:15,600 --> 02:03:17,680
PROVIDES A GREAT CONCEPTUAL

3503
02:03:17,680 --> 02:03:19,040
FRAMEWORK FOR US FOR MAPPING THE

3504
02:03:19,040 --> 02:03:23,200
NEURAL CIRCUITS THAT PRODUCE THE

3505
02:03:23,200 --> 02:03:24,400
GROOMING SEQUENCE, WHICH IS THE

3506
02:03:24,400 --> 02:03:25,680
CURRENT FOCUS OF OUR LAB.

3507
02:03:25,680 --> 02:03:31,960
IN THE WORK I'M PRESENTING TODAY

3508
02:03:31,960 --> 02:03:34,240
I WILL ONLY FOLK TUS ON THE

3509
02:03:34,240 --> 02:03:36,680
INPUT LAYER, BASICALLY THE

3510
02:03:36,680 --> 02:03:38,200
MECHANO-SENSORY NEURONS THOUGHT

3511
02:03:38,200 --> 02:03:39,840
TO DETECT THE DUST THAT

3512
02:03:39,840 --> 02:03:42,800
ACTIVATES EACH MOVEMENT IN

3513
02:03:42,800 --> 02:03:43,040
PARALLEL.

3514
02:03:43,040 --> 02:03:46,080
I WILL JUST FOCUS ON THE FLY

3515
02:03:46,080 --> 02:03:51,440
HEAD AND SHOW YOU HOW WE MAP

3516
02:03:51,440 --> 02:03:52,560
MECHANO SENSORY LOCATIONS FROM

3517
02:03:52,560 --> 02:03:54,720
DIFFERENT LOCATIONS ON THE HEAD

3518
02:03:54,720 --> 02:03:55,880
THROUGH DIFFERENT NEURONS INTO

3519
02:03:55,880 --> 02:03:56,480
THE BRAIN.

3520
02:03:56,480 --> 02:03:59,000
IN OUR PREVIOUSLY PUBLISHED AND

3521
02:03:59,000 --> 02:04:00,000
UNPUBLISHED LISHED WORK, WE HAVE

3522
02:04:00,000 --> 02:04:02,280
SHOWN THAT THE RELATION --

3523
02:04:02,280 --> 02:04:04,280
PUBLISHED AND UNPUBLISHED WORK

3524
02:04:04,280 --> 02:04:08,520
WE HAVE SHOWN THAT THE RELATION

3525
02:04:08,520 --> 02:04:11,920
OF CYTOMEGALY RESPONSES PROVIDE

3526
02:04:11,920 --> 02:04:13,440
THE GROOMING.

3527
02:04:13,440 --> 02:04:14,880
INROAD INTO THE GROOMING

3528
02:04:14,880 --> 02:04:15,120
NETWORK.

3529
02:04:15,120 --> 02:04:17,720
WHAT WE HAVE DONE IS TO

3530
02:04:17,720 --> 02:04:21,200
IDENTIFY, CLASSIFY AND QUANTIFY

3531
02:04:21,200 --> 02:04:24,080
ALL MECHANO SENSORY ON THE FLY

3532
02:04:24,080 --> 02:04:24,480
HEAD.

3533
02:04:24,480 --> 02:04:27,440
HERE WE USED A DRIVER LINE THAT

3534
02:04:27,440 --> 02:04:31,520
LABELS ALMOST ALL MECHANO

3535
02:04:31,520 --> 02:04:32,840
SENSORY NORMS, WHICH I WILL

3536
02:04:32,840 --> 02:04:35,880
REFER TO FOR THE REST OF THE

3537
02:04:35,880 --> 02:04:36,520
TALK.

3538
02:04:36,520 --> 02:04:39,920
WE IMAGED HEADS USING MICROSCOPE

3539
02:04:39,920 --> 02:04:43,360
AND WHAT WE OBSERVED WAS THAT

3540
02:04:43,360 --> 02:04:46,320
EACH BRISTLE IS IN-- IS

3541
02:04:46,320 --> 02:04:48,400
INNERVATED BY A SINGLE NEURON.

3542
02:04:48,400 --> 02:04:50,680
WE THEN RECONSTRUCTED THOSE ENDS

3543
02:04:50,680 --> 02:04:56,400
AND THEIR PROJECTIONS FROM THEIR

3544
02:04:56,400 --> 02:04:59,760
HEAD LOCATIONS IT THE BRAIN --

3545
02:04:59,760 --> 02:05:01,440
THEIR HEAD THROAKSZ THE BRAIN.

3546
02:05:01,440 --> 02:05:03,440
THIS REVEALED DIFFERENT PARTS OF

3547
02:05:03,440 --> 02:05:05,560
THE HEAD PROJECT TO THE BRAIN

3548
02:05:05,560 --> 02:05:10,160
THROUGH FOUR DIFFERENT NERVES.

3549
02:05:10,160 --> 02:05:12,040
HERE YOU CAN SEE THE

3550
02:05:12,040 --> 02:05:13,120
RECONSTRUCTED NERVES, NEURONS

3551
02:05:13,120 --> 02:05:16,840
AND THEIR NERVES IN DIFFERENT

3552
02:05:16,840 --> 02:05:19,240
COLORS, THE ANTENNA, ANTERIOR

3553
02:05:19,240 --> 02:05:21,120
HEAD, IN GREEN THE OCCIPITAL

3554
02:05:21,120 --> 02:05:23,840
NERVE, IN RED THE EYE NERVE,

3555
02:05:23,840 --> 02:05:27,000
BOTH ON THE POSTERIOR PART OF

3556
02:05:27,000 --> 02:05:35,000
THE HEAD AND PROJECT FROM

3557
02:05:35,000 --> 02:05:37,280
PROBOSCUS AND ALL THESE GO INTO

3558
02:05:37,280 --> 02:05:39,560
A REGION OF THE BRAIN SAZ.

3559
02:05:39,560 --> 02:05:41,560
IF YOU LOOK AT THE PROJECTIONS

3560
02:05:41,560 --> 02:05:45,600
TO GET THERE IN THIS DRIVER LINE

3561
02:05:45,600 --> 02:05:47,720
THAT TARGETS ALMOST ALL BNM'S,

3562
02:05:47,720 --> 02:05:50,280
IT IS IMPOSSIBLE TO DISTINGUISH

3563
02:05:50,280 --> 02:05:51,920
MOTOR NEURONS OR EVEN THE

3564
02:05:51,920 --> 02:05:52,760
DIFFERENT NERVES.

3565
02:05:52,760 --> 02:05:56,040
SO TO BE ABLE TO INDEPENDENTLY

3566
02:05:56,040 --> 02:05:57,800
LABEL AND VISUALIZE THE

3567
02:05:57,800 --> 02:05:59,360
DIFFERENT NERVES WE BUILD

3568
02:05:59,360 --> 02:06:00,640
DIFFERENT TRANSGENIC DRIVER LINE

3569
02:06:00,640 --> 02:06:05,880
AND HERE YOU CAN SEE THESE FOUR

3570
02:06:05,880 --> 02:06:07,640
LINES THAT LABEL NEURONS FROM

3571
02:06:07,640 --> 02:06:09,960
EITHER ONE NERVE IN THESE TWO

3572
02:06:09,960 --> 02:06:12,320
LINES INDEPENDENTLY OR TWO

3573
02:06:12,320 --> 02:06:15,080
NERVES IN THESE TWO LINES

3574
02:06:15,080 --> 02:06:16,080
INDEPENDENTLY, WHICH MAKES IT

3575
02:06:16,080 --> 02:06:18,560
MUCH EASIER TO VISUALIZE THE

3576
02:06:18,560 --> 02:06:21,640
NERVE PROJECTIONS INTO THE

3577
02:06:21,640 --> 02:06:22,160
BRAIN.

3578
02:06:22,160 --> 02:06:23,640
HOWEVER, WE NEXT WANTED TO

3579
02:06:23,640 --> 02:06:27,120
DETERMINE THE MORPHOLOGY OF

3580
02:06:27,120 --> 02:06:29,320
INDIVIDUAL BEINGS THAT INNERVATE

3581
02:06:29,320 --> 02:06:30,280
DISTINCT BRISTLES.

3582
02:06:30,280 --> 02:06:33,800
FOR THIS WE PERFORMED DYE FIELDS

3583
02:06:33,800 --> 02:06:35,560
THAT INNERVATE THE LARGEST

3584
02:06:35,560 --> 02:06:37,640
BRISTLES THE ON HEAD.

3585
02:06:37,640 --> 02:06:40,920
SO WHAT WE DID IS WE PLUCKED THE

3586
02:06:40,920 --> 02:06:42,080
POLICE HE WILL AND ADDED DYE

3587
02:06:42,080 --> 02:06:43,880
INTO THE EXPOSED SOCKET THAT

3588
02:06:43,880 --> 02:06:48,080
CONTAINS THE DENDRITE OF THE

3589
02:06:48,080 --> 02:06:49,320
ASSOCIATED BNM.

3590
02:06:49,320 --> 02:06:53,040
THE DYE THEN DIFFUSED INTO THE

3591
02:06:53,040 --> 02:06:55,000
NEURONS AND THE RESULTED YOU CAN

3592
02:06:55,000 --> 02:06:59,720
APPRECIATE HERE ON THE RIGHT

3593
02:06:59,720 --> 02:07:01,920
LABELED BNM'S.

3594
02:07:01,920 --> 02:07:05,080
FOR BRISTLES WE COULDN'T DYE, WE

3595
02:07:05,080 --> 02:07:07,240
USED VERY SMALL BRISTLES ON THE

3596
02:07:07,240 --> 02:07:08,320
BACK.

3597
02:07:08,320 --> 02:07:17,680
HEAD, WE USED STOIK --

3598
02:07:17,680 --> 02:07:18,640
STOICHIOASTICALLY GUIDELINES IN

3599
02:07:18,640 --> 02:07:21,280
THE DRIVER LINES.

3600
02:07:21,280 --> 02:07:23,440
SAME POPULATIONS HAVE VERY

3601
02:07:23,440 --> 02:07:25,400
SIMILAR MORPHOLOGY AS WE CAN SEE

3602
02:07:25,400 --> 02:07:30,560
HERE IN THESE ANTENNAE ENDS THAT

3603
02:07:30,560 --> 02:07:32,640
INNERVATE FOUR DISTINCT

3604
02:07:32,640 --> 02:07:34,720
BRISTLELESS ON THE ANTENNAE.

3605
02:07:34,720 --> 02:07:37,600
INTERESTINGLY, WHEN WE COMPARED

3606
02:07:37,600 --> 02:07:42,920
PROJECTIONS OF BNM ENDS THAT

3607
02:07:42,920 --> 02:07:47,440
INNERVATE NEIGHBORING

3608
02:07:47,440 --> 02:07:49,040
POPULATIONS, WE FOUND THEY ALSO

3609
02:07:49,040 --> 02:07:51,600
HAVE SIMILAR MORPHOLOGY.

3610
02:07:51,600 --> 02:07:53,800
SO NOW WE KNOW A LOT ABOUT THE

3611
02:07:53,800 --> 02:07:56,520
MORPHOLOGY OF INDIVIDUAL NEURONS

3612
02:07:56,520 --> 02:07:59,120
MPLETS HOWEVER, TO DEFINE THEIR

3613
02:07:59,120 --> 02:08:00,320
ORGANIZATION IN THE BRAIN, WE

3614
02:08:00,320 --> 02:08:03,280
NEEDED TO BE ABLE TO LOOK AT ALL

3615
02:08:03,280 --> 02:08:05,040
BNM'S TOGETHER WHILE KNOWING THE

3616
02:08:05,040 --> 02:08:08,880
IDENTITY OF THE BRISTLE THEY

3617
02:08:08,880 --> 02:08:09,160
INNERVATE.

3618
02:08:09,160 --> 02:08:12,920
SO FOR THIS, WE LOOKED IN A

3619
02:08:12,920 --> 02:08:14,120
SECTION ELECTRON MICROSCOPE

3620
02:08:14,120 --> 02:08:16,760
VOLUME OF AN ENTIRE FRUIT FLY

3621
02:08:16,760 --> 02:08:19,280
BRAIN FOR EACH OF THE NERVES TO

3622
02:08:19,280 --> 02:08:22,240
RECONSTRUCT ALL MECHANO SENSORY

3623
02:08:22,240 --> 02:08:23,320
NEURONS OF THE HEAD.

3624
02:08:23,320 --> 02:08:27,080
FOR THIS WE USED THE FLY WIRE AI

3625
02:08:27,080 --> 02:08:28,600
PLATFORM TO SEE EACH ENTIRE

3626
02:08:28,600 --> 02:08:30,360
NERVE AND RECONSTRUCT ALL

3627
02:08:30,360 --> 02:08:32,800
NEURONS, AND I'M SHOWING YOU ONE

3628
02:08:32,800 --> 02:08:37,120
EXAMPLE HERE, WHICH IS THE EYE

3629
02:08:37,120 --> 02:08:39,360
AND THE CAN -- NERVES MERGED

3630
02:08:39,360 --> 02:08:41,320
TOGETHER WEVMENT SEE THE ENTIRE

3631
02:08:41,320 --> 02:08:42,400
DISMERVES CONSTRUCTED ALL

3632
02:08:42,400 --> 02:08:45,000
NEURONS AND FROM THIS WE

3633
02:08:45,000 --> 02:08:50,400
IDENTIFIED 701 BNM'S OF THE

3634
02:08:50,400 --> 02:08:51,240
RECONSTRUCTED NEURONS.

3635
02:08:51,240 --> 02:08:54,760
SO WHAT WE FOUND IS THAT THE

3636
02:08:54,760 --> 02:08:57,840
BNM'S ARE SEW MATT TOPICALLY

3637
02:08:57,840 --> 02:08:59,480
ORGANIZED AS THEY'RE DISTINCT

3638
02:08:59,480 --> 02:09:01,080
PROJECTIONS FROM DIFFERENT

3639
02:09:01,080 --> 02:09:02,640
NERVES CORRESPOND TO DIFFERENT

3640
02:09:02,640 --> 02:09:05,120
BRISTLE LOCATIONS ON THE HEAD.

3641
02:09:05,120 --> 02:09:08,440
HERE YOU CAN SEE A FLY BRAIN AND

3642
02:09:08,440 --> 02:09:10,960
DIFFERENT ORIENTATIONS, THE

3643
02:09:10,960 --> 02:09:12,960
LATERAL, DORSAL AND ANTERIOR

3644
02:09:12,960 --> 02:09:16,800
VIEW, AND THE NERVE PROJECTIONS

3645
02:09:16,800 --> 02:09:19,200
MAGNIFIED AT THE BOTTOM HERE.

3646
02:09:19,200 --> 02:09:21,800
SO FOR EXAMPLE, BNM'S THAT

3647
02:09:21,800 --> 02:09:23,560
INNERVATE BRISTLES ON THE

3648
02:09:23,560 --> 02:09:25,080
PROBOSCIS PROJECT TO A DIFFERENT

3649
02:09:25,080 --> 02:09:29,240
AREA IN THE SEC THAN BNM'S THAT

3650
02:09:29,240 --> 02:09:30,640
INNERVAT THE EYES HERE.

3651
02:09:30,640 --> 02:09:32,840
I DON'T HAVE MUCH TIME TO SHOW

3652
02:09:32,840 --> 02:09:35,800
YOU THIS TODAY, BUT WE INCREASED

3653
02:09:35,800 --> 02:09:38,440
THE RESOLUTION OF THE SEW MATT

3654
02:09:38,440 --> 02:09:43,920
OH TOPIC MAP -- SOMATOTOPIC MAP

3655
02:09:43,920 --> 02:09:45,760
A LOT, ALMOST ALL THE BRISTLES

3656
02:09:45,760 --> 02:09:48,840
ON THE HEAD TO RECONSTRUCTED

3657
02:09:48,840 --> 02:09:49,320
NEURONS.

3658
02:09:49,320 --> 02:09:52,040
LET ME SUMMARIZE WHAT I JUSTBOU.

3659
02:09:52,040 --> 02:09:55,080
WE IDENTIFIED NEARLY ALL BNM'S

3660
02:09:55,080 --> 02:09:57,640
ON THE DROSOPHILA HEAD THAT

3661
02:09:57,640 --> 02:09:58,640
ELICITED GROOMING OF SPECIFIC

3662
02:09:58,640 --> 02:10:01,440
HEAD PARTS, WE RECONSTRUCTED BNM

3663
02:10:01,440 --> 02:10:02,440
PROJECTIONS FROM DIFFERENT

3664
02:10:02,440 --> 02:10:05,840
LOCATIONS ON THE HEAD TO THEIR

3665
02:10:05,840 --> 02:10:06,840
DISTINCT AREAS IN THE BRAIN

3666
02:10:06,840 --> 02:10:09,080
WHICH PROVIDES THE FIRST

3667
02:10:09,080 --> 02:10:14,920
SYNAPTIC RESOLUTION'S METATOPIC

3668
02:10:14,920 --> 02:10:18,640
MAP OF THE HEAD AND NEUROSENSORY

3669
02:10:18,640 --> 02:10:20,400
PATHWAYS WHICH IS HEAD FORMING,

3670
02:10:20,400 --> 02:10:22,760
GROUNDWORK TO ELUCIDATE PARALLEL

3671
02:10:22,760 --> 02:10:24,000
ARCHITECTURE THAT UNDERLIES EACH

3672
02:10:24,000 --> 02:10:26,280
OF THE HEAD GROOMING MOVEMENTS.

3673
02:10:26,280 --> 02:10:28,600
THIS IS ALL A MAJOR CONTRIBUTION

3674
02:10:28,600 --> 02:10:31,440
TO FLY WIRE TO INCORPORATE INTO

3675
02:10:31,440 --> 02:10:34,400
THEIR FLYI  BRAINULD LIKE TO THL

3676
02:10:34,400 --> 02:10:36,680
THE PEOPLE THAT HAVE BEEN

3677
02:10:36,680 --> 02:10:39,520
INVOLVED IN THE PROJECT,

3678
02:10:39,520 --> 02:10:43,360
ESPECIALLY ANDY, CATARINA AND

3679
02:10:43,360 --> 02:10:45,520
ANDIVA WHO WERE THE MAIN

3680
02:10:45,520 --> 02:10:47,080
CONTRIBUTORS TORS, NIH BRAIN

3681
02:10:47,080 --> 02:10:49,040
INITIATIVE AND NIH CORPORATE WHO

3682
02:10:49,040 --> 02:10:50,800
ARE FUNDING THIS PROJECT, AND I

3683
02:10:50,800 --> 02:10:53,200
WOULD LIKE TO THANK YOU FOR

3684
02:10:53,200 --> 02:10:54,760
INVITING ME TO PRESENTED TODAY

3685
02:10:54,760 --> 02:10:56,800
AND FOR YOUR ATTENTION.

3686
02:10:56,800 --> 02:10:59,400
THANK YOU.

3687
02:10:59,400 --> 02:11:02,480
>> GOOD OOIVE, EVERYONE --
GOOD

3688
02:11:02,480 --> 02:11:04,040
AFTERNOON, EVERYONE, MY NAME IS

3689
02:11:04,040 --> 02:11:06,560
MICHAEL REISER, GROUP LEADER, MY

3690
02:11:06,560 --> 02:11:08,640
WORK IS ON -- FLIES.

3691
02:11:08,640 --> 02:11:10,160
TODAY I'LL TELL YOU ABOUT MY

3692
02:11:10,160 --> 02:11:11,440
LAB'S EXPLORATION FOLLOWING

3693
02:11:11,440 --> 02:11:12,960
VISUAL PATHWAYS OUTSIDE OF THE

3694
02:11:12,960 --> 02:11:14,280
VISUAL SYSTEM WHICH IS A

3695
02:11:14,280 --> 02:11:15,320
SLIGHTLY UNUSUAL THING TO DO AND

3696
02:11:15,320 --> 02:11:17,080
I'LL TELL YOU ABOUT IT AS WE

3697
02:11:17,080 --> 02:11:18,640
MOVE ON AND THE WAY WE'VE

3698
02:11:18,640 --> 02:11:20,400
APPROACHED THIS PROBLEM IS BY

3699
02:11:20,400 --> 02:11:21,360
COMBINING FUNCTIONAL

3700
02:11:21,360 --> 02:11:24,000
MEASUREMENTS WITH CONNECTOMIC

3701
02:11:24,000 --> 02:11:24,600
ANALYSIS.

3702
02:11:24,600 --> 02:11:26,840
AND SO AS YOU MAY KNOW, VISION

3703
02:11:26,840 --> 02:11:29,920
IS VERY PROMINENT IN THE BRAIN

3704
02:11:29,920 --> 02:11:32,000
OF SIGHTED ANIMALS AND WHEN WE

3705
02:11:32,000 --> 02:11:33,720
SEE THAT BY LOOKING FOR EXAMPLE

3706
02:11:33,720 --> 02:11:35,520
AT THE AMOUNT OF CORTICAL REAL

3707
02:11:35,520 --> 02:11:39,680
ESTATE DEDICATED TO VISION IN MY

3708
02:11:39,680 --> 02:11:42,080
FAVORITE ORGANISM IT THE FLY,

3709
02:11:42,080 --> 02:11:42,960
CROSS-SECTION OF THE FLY BRAIN

3710
02:11:42,960 --> 02:11:44,400
AND LOOK AT AGAIN REAL ESTATE,

3711
02:11:44,400 --> 02:11:46,120
WE FIND THAT HALF THE BRAIN IS

3712
02:11:46,120 --> 02:11:47,240
DEDICATED TO VISION AND THAT'S

3713
02:11:47,240 --> 02:11:48,240
WHETHER YOU THINK ABOUT VOLUME

3714
02:11:48,240 --> 02:11:50,400
OR THE NUMBER OF NEURONS.

3715
02:11:50,400 --> 02:11:52,080
THINKING ABOUT THIS, ONE OF THE

3716
02:11:52,080 --> 02:11:53,600
REASONS WHY VISION TAKES UP SO

3717
02:11:53,600 --> 02:11:57,200
MUCH SPACE IS BECAUSE OF RETINA,

3718
02:11:57,200 --> 02:11:58,600
HERE IN THE FLY BRAIN WE CAN SEE

3719
02:11:58,600 --> 02:12:00,160
THAT IF WE FOLLOW THE VISUAL

3720
02:12:00,160 --> 02:12:01,240
INFORMATION FROM A PARTICULAR

3721
02:12:01,240 --> 02:12:03,360
POINT IN SPACE AND WE FOLLOW IT

3722
02:12:03,360 --> 02:12:05,200
THROUGH COLUMNAR NEURONS THROUGH

3723
02:12:05,200 --> 02:12:06,200
DIFFERENT NEURAL FIELDS IN THE

3724
02:12:06,200 --> 02:12:07,640
VISUAL SYSTEM WHAT WE HAVE IS WE

3725
02:12:07,640 --> 02:12:10,120
HAVE SETS OF NEURONS WHICH ARE

3726
02:12:10,120 --> 02:12:11,760
DEDICATED TO IMAGING INFORMATION

3727
02:12:11,760 --> 02:12:13,960
FROM A PARTICULAR REGION AND

3728
02:12:13,960 --> 02:12:15,600
SPACE AND THEY MAINTAIN THE

3729
02:12:15,600 --> 02:12:17,240
SPATIAL RELATIONSHIP BETWEEN

3730
02:12:17,240 --> 02:12:19,080
DIFFERENT PARTS OF THE VISUAL

3731
02:12:19,080 --> 02:12:21,160
FIELD WHILE FEATURES ARE BEING

3732
02:12:21,160 --> 02:12:21,480
EXTRACTED.

3733
02:12:21,480 --> 02:12:23,480
SO THIS ORGANIZATION HAS BEEN

3734
02:12:23,480 --> 02:12:24,920
INCREDIBLY USEFUL, FOR EXAMPLE,

3735
02:12:24,920 --> 02:12:26,760
IN STUDYING THE ORIGIN OF

3736
02:12:26,760 --> 02:12:28,320
DIRECTIONAL SELECTIVITY AND THE

3737
02:12:28,320 --> 02:12:30,240
ORGANIZATION OF MOTION VISION.

3738
02:12:30,240 --> 02:12:32,120
SO WHAT WE'VE BEEN WONDERING IS

3739
02:12:32,120 --> 02:12:33,400
WHAT HAPPENS WHEN YOU LEAVE THE

3740
02:12:33,400 --> 02:12:34,600
VISUAL SYSTEM?

3741
02:12:34,600 --> 02:12:39,640
SO THAT ORGANIZATION OF VISUAL

3742
02:12:39,640 --> 02:12:40,880
RETINA -- HAS BEEN VERY HELPFUL

3743
02:12:40,880 --> 02:12:43,160
IN THINKING ABOUT FEATURE

3744
02:12:43,160 --> 02:12:44,240
DETECTION, BUT WHAT HAPPENS WHEN

3745
02:12:44,240 --> 02:12:46,240
YOU NO LONGER HAVE THIS WELL

3746
02:12:46,240 --> 02:12:47,120
ORGANIZED STRUCTURE.

3747
02:12:47,120 --> 02:12:47,960
THAT'S WHAT WE'VE BEEN LOOKING

3748
02:12:47,960 --> 02:12:50,160
AT ASK DOING THIS RECENT BILL

3749
02:12:50,160 --> 02:12:52,880
FOCUSING A SET OF NEURONS CALLED

3750
02:12:52,880 --> 02:12:54,680
LC NEURONS, NEURONS WHICH

3751
02:12:54,680 --> 02:12:57,360
RECEIVE THEIR INPUTS HERE IN THE

3752
02:12:57,360 --> 02:12:59,040
LOBULA WHERE THEY HAVE DENDRITES

3753
02:12:59,040 --> 02:13:02,000
IN THIS CELL TYPE LC6 CASE WHICH

3754
02:13:02,000 --> 02:13:03,560
CORE TO UNDERSTAND TO 4 PERCENT

3755
02:13:03,560 --> 02:13:06,600
OF THE FIELD OF THE FLY AND

3756
02:13:06,600 --> 02:13:08,160
DENDRITES ARE ORGANIZED AND

3757
02:13:08,160 --> 02:13:12,440
RECEIVE INPUTS FROM RETINA

3758
02:13:12,440 --> 02:13:13,960
TOPIC, CONNECT TO GLOMERULUS

3759
02:13:13,960 --> 02:13:16,360
WHERE A LOT OF THAT ORGANIZATION

3760
02:13:16,360 --> 02:13:17,440
IS NO LONGER EVIDENT AS YOU CAN

3761
02:13:17,440 --> 02:13:18,200
SEE HERE.

3762
02:13:18,200 --> 02:13:19,840
THERE'S BEEN THE PROPOSAL THIS

3763
02:13:19,840 --> 02:13:21,040
REPRESENTS SOME ABSTRACTION OF

3764
02:13:21,040 --> 02:13:22,160
VISUAL INFORMATION BUT THAT'S

3765
02:13:22,160 --> 02:13:22,920
THE OPEN QUESTION.

3766
02:13:22,920 --> 02:13:23,960
THAT'S WHAT WE'VE BEEN THINKING

3767
02:13:23,960 --> 02:13:25,200
ABOUT IS HOW DOES VISION GET

3768
02:13:25,200 --> 02:13:27,960
SORT OF REFORMATTED AS YOU CROSS

3769
02:13:27,960 --> 02:13:29,280
THIS LAYER OF THE BRAIN WHERE

3770
02:13:29,280 --> 02:13:31,840
YOU GO FROM VERY WELL ORGANIZED

3771
02:13:31,840 --> 02:13:33,600
VISUAL STRUCTURES TO NONVISUAL

3772
02:13:33,600 --> 02:13:35,320
OR NOT OBVIOUSLY VISUAL

3773
02:13:35,320 --> 02:13:35,800
ORGANIZATION.

3774
02:13:35,800 --> 02:13:37,000
SO WE'VE APPROACHED THIS PROBLEM

3775
02:13:37,000 --> 02:13:39,280
IN THE WAY ME AND A LOT OF MY

3776
02:13:39,280 --> 02:13:41,560
COG LEAGUES HAVE A-- COLLEAGUES

3777
02:13:41,560 --> 02:13:42,480
HAVE APPROACHED MANY PROBLEMS IN

3778
02:13:42,480 --> 02:13:43,640
THE FLY WHICH IS FIRST BY

3779
02:13:43,640 --> 02:13:46,080
STARTING WITH A SYSTEMATIC SET

3780
02:13:46,080 --> 02:13:47,160
OF GENETIC DRIVER LINES WHICH

3781
02:13:47,160 --> 02:13:49,000
ALLOW US TO TARG THE NEURONS ONE

3782
02:13:49,000 --> 02:13:50,440
CELL TYPE AT A TIEMENT WHICH

3783
02:13:50,440 --> 02:13:52,840
ALLOWS US TO DO THESE SORT OF

3784
02:13:52,840 --> 02:13:54,040
HIGH-QUALITY ANATOMIC

3785
02:13:54,040 --> 02:13:55,400
DESCRIPTIVE STUDIES AND THEN WE

3786
02:13:55,400 --> 02:13:57,800
ALSO HAVE TOOLS WE CAN USE FOR

3787
02:13:57,800 --> 02:13:58,440
FUNCTIONAL STUDIES.

3788
02:13:58,440 --> 02:14:01,440
SO WE FOCUS QUITE A BIT ON LC6

3789
02:14:01,440 --> 02:14:02,600
WHICH WAS THE FIRST NEURON I

3790
02:14:02,600 --> 02:14:03,720
JUST SHOWED AND THE ONE WE USE

3791
02:14:03,720 --> 02:14:05,240
TO THINK ABOUT THE ORGANIZATION

3792
02:14:05,240 --> 02:14:07,400
WITHIN A GLOMERULUS, LC6 IS THE

3793
02:14:07,400 --> 02:14:08,520
ONE HERE IN BLUE.

3794
02:14:08,520 --> 02:14:10,360
AS YOU CAN SEE THERE ARE MANY

3795
02:14:10,360 --> 02:14:12,240
GLOMER LIE AND THEY PROJECT

3796
02:14:12,240 --> 02:14:16,280
IN -- GLOMERULI AND THEY PROJECT

3797
02:14:16,280 --> 02:14:18,480
IN PARALLEL INTO THE BRAIN.

3798
02:14:18,480 --> 02:14:18,640
FLY.

3799
02:14:18,640 --> 02:14:19,920
I WANT TO MENTION THAT PUBLISHED

3800
02:14:19,920 --> 02:14:21,760
A FEW YEARS AGO WE HAD A STUDY

3801
02:14:21,760 --> 02:14:22,760
WHERE WE LOOKED AT THE

3802
02:14:22,760 --> 02:14:24,040
ORGANIZATION WITHIN A

3803
02:14:24,040 --> 02:14:25,040
GLOMERULUS, FOLLOWED NEURONS

3804
02:14:25,040 --> 02:14:26,800
INTO THE GLOMERULUS, FOUND THEIR

3805
02:14:26,800 --> 02:14:28,080
TARGETS AND THOUGHT ABOUT HOW

3806
02:14:28,080 --> 02:14:30,840
WITHIN THE GLOMERULUS THE

3807
02:14:30,840 --> 02:14:31,680
READOUT, WHAT KIND OF

3808
02:14:31,680 --> 02:14:33,120
INFORMATION IS IN THAT READOUT

3809
02:14:33,120 --> 02:14:35,280
FROM A GLOMERULUS AND THEN THE

3810
02:14:35,280 --> 02:14:36,680
STUDY I'LL TELL YOU ABOUT TODAY

3811
02:14:36,680 --> 02:14:38,120
IS ONE THAT WAS JUST PUBLISHED A

3812
02:14:38,120 --> 02:14:39,720
MONTH AGO WHERE THIS WAS A STUDY

3813
02:14:39,720 --> 02:14:44,040
LED BY NATHAN WHO IS A JOINT

3814
02:14:44,040 --> 02:14:45,360
POST-DOC AND WE WERE LOOKING AT

3815
02:14:45,360 --> 02:14:50,880
THE READOUT ACROSS GLOMERULI AND

3816
02:14:50,880 --> 02:14:52,120
MIGHT 2E8 YOU HOW THEY ARE ORG

3817
02:14:52,120 --> 02:14:53,560
NIERLTZED AND WHY THEY ARE WHERE

3818
02:14:53,560 --> 02:14:53,880
THEY ARE.

3819
02:14:53,880 --> 02:14:55,600
IN BOTH STARTED WITH FUNCTIONAL

3820
02:14:55,600 --> 02:14:57,640
IN THE LAB AND VERY QUICKLY

3821
02:14:57,640 --> 02:14:58,840
REALIZED THAT THESE STUDIES

3822
02:14:58,840 --> 02:15:02,040
WOULD BE POWERFULLY INFORMED BY

3823
02:15:02,040 --> 02:15:02,840
CONNECTOMIC DATASET.

3824
02:15:02,840 --> 02:15:04,240
IN THE FIRST INDICATE WE

3825
02:15:04,240 --> 02:15:05,880
MANUALLY RECONSTRUCTED LC

3826
02:15:05,880 --> 02:15:07,280
'6NEURONS AND THEIR TARGETS INTO

3827
02:15:07,280 --> 02:15:08,680
THE GLOMERULUS AND CENTRAL BRAIN

3828
02:15:08,680 --> 02:15:10,480
AND SECOND STUDY WE WERE ABLE TO

3829
02:15:10,480 --> 02:15:13,160
TAKE ADVANTAGE OF THE NOW VERY

3830
02:15:13,160 --> 02:15:15,360
FAMOUS HEMIBRAIN CONNECTOME TO

3831
02:15:15,360 --> 02:15:18,120
LOOK AT THE CONNECTIVITY OUT OF

3832
02:15:18,120 --> 02:15:20,840
THESE GLOMER DAIRN GLOMERULI

3833
02:15:20,840 --> 02:15:22,920
WITHIN THE CENTRAL BRAIN.

3834
02:15:22,920 --> 02:15:24,920
S EVEN THOUGH QUITE A FEW THINGS

3835
02:15:24,920 --> 02:15:26,240
HAVE BEEN SAID ABOUT THESE SINCE

3836
02:15:26,240 --> 02:15:27,880
WE PUBLISHED THAT PAPER SIX

3837
02:15:27,880 --> 02:15:29,120
MONTHS AGO THERE'S A LOT WE

3838
02:15:29,120 --> 02:15:30,280
DON'T KNOW ABOUT THEIR EN

3839
02:15:30,280 --> 02:15:32,240
CAIDING SO NATHAN TOOK ON THIS

3840
02:15:32,240 --> 02:15:34,320
FLOB A SOPHISTICATED WAY BY

3841
02:15:34,320 --> 02:15:36,640
DOING VOLUME MELT TRICK IMAGING,

3842
02:15:36,640 --> 02:15:38,840
TWO PHOTON VOLUMETRIC IMAGING,

3843
02:15:38,840 --> 02:15:40,360
NOT IN GLOMERULUS OR VISUAL

3844
02:15:40,360 --> 02:15:41,600
SYSTEM BUT IN THE REGION BETWEEN

3845
02:15:41,600 --> 02:15:44,160
THEM WHERE THE NEURONS CAN BE

3846
02:15:44,160 --> 02:15:45,200
INDIVIDUALLY SEGMENTED ALLOWING

3847
02:15:45,200 --> 02:15:46,320
YOU TO DO A POWERFUL

3848
02:15:46,320 --> 02:15:47,480
EXPERIMENTAL APPROACH WHERE YOU

3849
02:15:47,480 --> 02:15:49,040
CAN MAP RECEPTIVE FIELDS OF

3850
02:15:49,040 --> 02:15:50,360
INDIVIDUAL NEURONS, DISTINGUISH

3851
02:15:50,360 --> 02:15:52,640
THEM BASED ON THE

3852
02:15:52,640 --> 02:15:54,400
THREE-DIMENSIONAL ROI'S FOR THE

3853
02:15:54,400 --> 02:15:56,560
NEURONS AND THEN YOU CAN DELIVER

3854
02:15:56,560 --> 02:15:59,200
VISUAL STIMULI CENTERED ON THE

3855
02:15:59,200 --> 02:16:00,400
RECEPTIVE FIELD CENTER WHICH HAD

3856
02:16:00,400 --> 02:16:02,080
BEEN MAPPED OUT FOR EACH NEURON

3857
02:16:02,080 --> 02:16:03,960
AND THAT GIVES YOU ACCESS TO A

3858
02:16:03,960 --> 02:16:06,040
LEVEL OF DESCRIPTION OF THE

3859
02:16:06,040 --> 02:16:07,600
FUNCTIONAL CELL ACTIVITY OF

3860
02:16:07,600 --> 02:16:09,560
KNEES NEURONS WHICH HAD NOT BEEN

3861
02:16:09,560 --> 02:16:10,200
PREVIOUSLY POSSIBLE.

3862
02:16:10,200 --> 02:16:11,320
SO A SIMPLE THING YOU WOULD

3863
02:16:11,320 --> 02:16:12,920
MEASURE DOING THIS IS JUST ASK

3864
02:16:12,920 --> 02:16:14,880
HOW LARGE ARE THE RECEPTORS OF

3865
02:16:14,880 --> 02:16:16,000
THESE NEURONS AND YOU CAN DO

3866
02:16:16,000 --> 02:16:17,520
THAT HERE AND SEE THAT WHEN WE

3867
02:16:17,520 --> 02:16:18,640
COMPARE THIS FUNCTIONAL

3868
02:16:18,640 --> 02:16:20,560
MEASUREMENT TO THE ANATOMICAL

3869
02:16:20,560 --> 02:16:22,240
MEASUREMENT, WE FIND EXCELLENT

3870
02:16:22,240 --> 02:16:23,120
CONCORD ANSWER.

3871
02:16:23,120 --> 02:16:25,160
SNRIET IN GENERAL, NEURONS WITH

3872
02:16:25,160 --> 02:16:27,160
LARGER DENDRITES HAVE LARGER

3873
02:16:27,160 --> 02:16:29,000
RECEPTIVE FIELDS, BUT THAT'S THE

3874
02:16:29,000 --> 02:16:31,400
KIND OF -- THAT'S NOT REALLY THE

3875
02:16:31,400 --> 02:16:32,600
OPTIMIZED THING FOR THESE

3876
02:16:32,600 --> 02:16:33,480
NEURONS, THIS IS JUST THE

3877
02:16:33,480 --> 02:16:35,240
MAPPING STIMULUS BUT WHAT NATHAN

3878
02:16:35,240 --> 02:16:37,400
DID IS A SYSTEMATIC WAY DELIVER

3879
02:16:37,400 --> 02:16:39,840
A WHOLE PANEL OF STIMULI TO

3880
02:16:39,840 --> 02:16:41,520
THESE NEURONS WHICH ALLOWED HIM

3881
02:16:41,520 --> 02:16:44,240
TO DESCRIBE THE RESPONSE THROUGH

3882
02:16:44,240 --> 02:16:45,760
A WHOLE RANGE OF STIMULI, HERE

3883
02:16:45,760 --> 02:16:47,640
IS AN EXAMPLE FOR ONE CELL TYPE

3884
02:16:47,640 --> 02:16:49,080
BUT THEN HERE IS THE SET OF THE

3885
02:16:49,080 --> 02:16:51,320
TEN LC'S THAT NATHAN LOOKED AT

3886
02:16:51,320 --> 02:16:53,120
CAREFULLY AND WHAT WE FIND AGAIN

3887
02:16:53,120 --> 02:16:54,960
THESE ARE STIMULI DELIVERED TO A

3888
02:16:54,960 --> 02:16:56,840
CENTER OF THE RECEPTOR FIELD

3889
02:16:56,840 --> 02:16:58,160
MAPPED FOR EACH INDIVIDUAL

3890
02:16:58,160 --> 02:16:59,600
NEURON WHAT WE FIND IS THAT AT

3891
02:16:59,600 --> 02:17:01,440
THE HIGH LEVEL YOU CAN CUT THESE

3892
02:17:01,440 --> 02:17:04,000
NEURONS INTO TWO GROUPS, A GROUP

3893
02:17:04,000 --> 02:17:05,960
THAT PRIMARILY RESPONDS TO SMALL

3894
02:17:05,960 --> 02:17:07,600
OBJECT MOTION AND A GROUP THAT

3895
02:17:07,600 --> 02:17:09,400
PRIMARILY RESPONDS TO VISUAL

3896
02:17:09,400 --> 02:17:11,200
LUMEN SO EXPANDING THIS STIMULI

3897
02:17:11,200 --> 02:17:12,280
AND THEN WITHIN THE GROUPS

3898
02:17:12,280 --> 02:17:13,680
THERE'S A LOT OF DETAILS WHICH

3899
02:17:13,680 --> 02:17:15,120
I'LL POINTED YOU TO THE PAPER TO

3900
02:17:15,120 --> 02:17:16,560
LOOK INTO FURTHER.

3901
02:17:16,560 --> 02:17:18,080
BUT THAT IS JUST KEEP THAT IN

3902
02:17:18,080 --> 02:17:20,800
MIND AT THE FIRST LEVEL OF THIS

3903
02:17:20,800 --> 02:17:22,000
SMALL OBJECT.

3904
02:17:22,000 --> 02:17:23,880
SO THEN WE THEN GO BACK TO THIS

3905
02:17:23,880 --> 02:17:27,720
QUESTION OF ASKING HOW ARE THE

3906
02:17:27,720 --> 02:17:28,920
GLOMERULI ORG NIEDZED AND IT'S

3907
02:17:28,920 --> 02:17:30,880
IMPORTANT TO POINT OUT THEY DO

3908
02:17:30,880 --> 02:17:32,640
FORM THIS VISUALLY CONFIGUREOUS

3909
02:17:32,640 --> 02:17:35,520
GROUP OF GLOMERULI IN THE BRAIN

3910
02:17:35,520 --> 02:17:37,560
AND WE CAN START TO IMPOSE THE

3911
02:17:37,560 --> 02:17:38,760
LAINLZ, THESE FUNCTIONAL LABELS

3912
02:17:38,760 --> 02:17:41,600
BACK ONTO THE NEURONS AND INDEED

3913
02:17:41,600 --> 02:17:43,600
SO THE LABELS OF THE LUMEN GROUP

3914
02:17:43,600 --> 02:17:45,240
AND OBJECT GROUP AND WE FIND WE

3915
02:17:45,240 --> 02:17:48,040
ALREADY HAVE A PRETTY GOOD CLUE

3916
02:17:48,040 --> 02:17:50,480
THAT LOOMING NEURONS ARE NEXT TO

3917
02:17:50,480 --> 02:17:54,000
LOOMING NEURONS AND ANOTHER WAY

3918
02:17:54,000 --> 02:17:58,200
TO SEE THAT IS BY LOOKING AT

3919
02:17:58,200 --> 02:17:59,160
PRINCIPAL COMPONENT ANALYSIS OF

3920
02:17:59,160 --> 02:18:00,720
ALL THE RESPONSES ACROSS ALL THE

3921
02:18:00,720 --> 02:18:02,600
MEASUREMENTS IN THAT DATASET AND

3922
02:18:02,600 --> 02:18:05,920
HERE EACH DOT REPRESENTS THE

3923
02:18:05,920 --> 02:18:07,360
RESPONSES OF A SINGLE NEURON AND

3924
02:18:07,360 --> 02:18:11,720
YOU CAN SEE THAT ALL THE NEURONS

3925
02:18:11,720 --> 02:18:12,480
CO-CLUSTER, SO ALL OF THE

3926
02:18:12,480 --> 02:18:13,600
INDIVIDUALS OF ONE CELL TYPE

3927
02:18:13,600 --> 02:18:14,880
HAVE RESPONSES THAT ARE MORE

3928
02:18:14,880 --> 02:18:16,280
SIMILAR TO THE OTHER NEURONS OF

3929
02:18:16,280 --> 02:18:24,080
THE CELL TYPE, AND WE ALSO FIND

3930
02:18:24,080 --> 02:18:25,960
THAT THE SPATIAL POSITION OF THE

3931
02:18:25,960 --> 02:18:27,120
NEURONS IN THE BRAIN LOOKS QUITE

3932
02:18:27,120 --> 02:18:28,560
A BIT LIKE HOW THEY'RE POSITION

3933
02:18:28,560 --> 02:18:31,240
IN THIS PCA SPACE SO FOR EXAMPLE

3934
02:18:31,240 --> 02:18:34,360
IF YOU'RE LC15 AND LC25 ARE

3935
02:18:34,360 --> 02:18:37,640
CLOSE AND AGAIN LPLC2 AND 4 ARE

3936
02:18:37,640 --> 02:18:42,240
ALSO CLOSE NOW AND RARELY ARE IN

3937
02:18:42,240 --> 02:18:45,840
MY HANDS ARE A PCA ANALYSIS,

3938
02:18:45,840 --> 02:18:47,640
PRINCIPAL EXEENLT CIS, HERE

3939
02:18:47,640 --> 02:18:49,120
INDEED IT REALLY LOOK AS IF

3940
02:18:49,120 --> 02:18:50,240
PRINCIPAL COMPONENT ONE IS

3941
02:18:50,240 --> 02:18:51,880
DESCRIBING THE NEURON'S RESPONSE

3942
02:18:51,880 --> 02:18:55,400
SIFT TO LUMEN WHEREAS THE SKD

3943
02:18:55,400 --> 02:18:57,360
PRINCIPAL COMPONENT IS LARNLLY

3944
02:18:57,360 --> 02:18:59,080
DESCRIBING THE NEURON'S RESPONSE

3945
02:18:59,080 --> 02:19:02,680
TO SIZE, WHAT ELSE THE OPTIMAL

3946
02:19:02,680 --> 02:19:04,800
BEST SIZE STIMULUS WHICH DRIVES

3947
02:19:04,800 --> 02:19:05,760
THE NEURON.

3948
02:19:05,760 --> 02:19:07,720
IT I HOPE I'VE CONVINCED YOU

3949
02:19:07,720 --> 02:19:11,160
THAT NEARBY BINEURONS HAVE MORE

3950
02:19:11,160 --> 02:19:15,320
SIMILAR RESPONSES, THESE

3951
02:19:15,320 --> 02:19:17,040
GLOMERULI ARE ORGANIZED INTO A

3952
02:19:17,040 --> 02:19:18,040
FEATURE MAP AND WE WANT TOP

3953
02:19:18,040 --> 02:19:20,400
WHETHER THE BRAIN CAN USE THAT

3954
02:19:20,400 --> 02:19:21,840
FEATURE MAP AND LOOK AT

3955
02:19:21,840 --> 02:19:22,960
DOWNSTREAM NEURON AND ASK

3956
02:19:22,960 --> 02:19:24,240
WHETHER THEIR READOUT SUGGESTS

3957
02:19:24,240 --> 02:19:26,120
THAT THEY'RE READING FROM

3958
02:19:26,120 --> 02:19:27,880
SPECIFICALLY NEARBY GLOMER LIE

3959
02:19:27,880 --> 02:19:31,480
AND WE DO THAT WITH CONNECTOME,

3960
02:19:31,480 --> 02:19:36,280
USING HEMIBRAIN TO DO THIS AND I

3961
02:19:36,280 --> 02:19:38,160
CAN'T SHOW YOU HOW REMARKABLY

3962
02:19:38,160 --> 02:19:39,360
STEREOTYPED THESE BRAINS ARE.

3963
02:19:39,360 --> 02:19:41,680
TOP IMAGES FROM LIGHT MICROSCOPY

3964
02:19:41,680 --> 02:19:45,080
BASED ON LABELING P BARS,

3965
02:19:45,080 --> 02:19:46,800
PRESYNAPTIC ACTIVE ZONES OF

3966
02:19:46,800 --> 02:19:48,440
NEURONS, A COMPOSITE OF TEN

3967
02:19:48,440 --> 02:19:49,440
DIFFERENT BRAINS, WE HAVE

3968
02:19:49,440 --> 02:19:50,680
ANOTHER BRAIN, ELEVENTH BRAIN

3969
02:19:50,680 --> 02:19:52,200
WHICH IS THE ONE THAT THE

3970
02:19:52,200 --> 02:19:53,400
CONNECT TOMORROW EXISTS FOR AND

3971
02:19:53,400 --> 02:19:54,800
WE JUST COLOR CODE IT IN THE

3972
02:19:54,800 --> 02:19:55,800
SAME WAY AND I THINK IF YOU

3973
02:19:55,800 --> 02:19:58,200
STARE AT THIS FOR A WHILE YOU'LL

3974
02:19:58,200 --> 02:19:59,720
SEE EVEN AT THE FINE DEGREE

3975
02:19:59,720 --> 02:20:01,480
THERE'S A HUGE CONCORDANCE

3976
02:20:01,480 --> 02:20:04,520
BETWEEN THESE TWO DATASETS, IT

3977
02:20:04,520 --> 02:20:06,480
ALLOWS US TO MAKE THESE LEAPS

3978
02:20:06,480 --> 02:20:08,480
CROSS DIFFERENT ANIMALS AND

3979
02:20:08,480 --> 02:20:11,120
USING THIS CELL TYPE AS THE

3980
02:20:11,120 --> 02:20:12,200
CURRENCY FOR THE COMPARISON THAT

3981
02:20:12,200 --> 02:20:13,520
WE CARRY ACROSS.

3982
02:20:13,520 --> 02:20:14,640
SO NOW FOR THIS QUESTION.

3983
02:20:14,640 --> 02:20:18,360
ARE THE NEIGHBORING GLO ME RULI

3984
02:20:18,360 --> 02:20:22,160
IN A VISUAL MAP USED IN SHARED

3985
02:20:22,160 --> 02:20:22,560
COMPUTATION?

3986
02:20:22,560 --> 02:20:24,040
WE USE THIS, WE CAN JUST ASK

3987
02:20:24,040 --> 02:20:25,400
WHETHER NEURONS THAT READ OUT

3988
02:20:25,400 --> 02:20:29,120
FROM PAIRS OF COLUMNAR CELLS ARE

3989
02:20:29,120 --> 02:20:31,280
THEY MORE LIKELY TO READ OUT

3990
02:20:31,280 --> 02:20:34,880
FROM GLOMERULI THAT ARE CLOSE

3991
02:20:34,880 --> 02:20:35,040
BY?

3992
02:20:35,040 --> 02:20:35,840
INDEED THEY ARE.

3993
02:20:35,840 --> 02:20:37,000
PAIRINGS ARE SIGNIFICANTLY

3994
02:20:37,000 --> 02:20:40,360
SKEWED TOWARDS NEARBY GLOMERULI

3995
02:20:40,360 --> 02:20:43,000
AS OPPOSED TO JUST RANDOMLY

3996
02:20:43,000 --> 02:20:44,240
SHUFFLE AND POST CONNECTIONS.

3997
02:20:44,240 --> 02:20:46,400
APPEARS I MIGHT SUSPECT, THE

3998
02:20:46,400 --> 02:20:47,800
PROXIMITY AND FUNCTIONAL

3999
02:20:47,800 --> 02:20:49,480
SIMILARITY, INDEED WE FIND

4000
02:20:49,480 --> 02:20:50,640
SLAIRL THESE PAIRINGS ARE SKEWED

4001
02:20:50,640 --> 02:20:52,560
TOWARDS INPUTS THAT ENCODE

4002
02:20:52,560 --> 02:20:54,160
SIMILAR VISUAL FEATURES.  SO WE

4003
02:20:54,160 --> 02:20:56,120
FIND THAT ON AVERAGE, THE

4004
02:20:56,120 --> 02:20:57,680
TARGETS IN THE CENTRAL BRAIN ARE

4005
02:20:57,680 --> 02:21:02,400
REEKED OUT FROM NEARBY GLOMERULI

4006
02:21:02,400 --> 02:21:04,040
WITH SIMILAR FEATURES, THIS IS A

4007
02:21:04,040 --> 02:21:05,080
HIGH LEVEL RESULT AND WHAT'S

4008
02:21:05,080 --> 02:21:07,200
BEAUTIFUL IS THAT THEN YOU HAVE

4009
02:21:07,200 --> 02:21:08,400
ACCESS TO ALL THE DETAILS.

4010
02:21:08,400 --> 02:21:10,040
SO INDEED WE CAN LOOK AT ALL THE

4011
02:21:10,040 --> 02:21:11,480
PAIRS THAT EXIST IN THE BRAIN,

4012
02:21:11,480 --> 02:21:12,760
THERE'S A SUMMARY HERE WHICH

4013
02:21:12,760 --> 02:21:13,960
I'LL POINTED YOU TO THE PAPER

4014
02:21:13,960 --> 02:21:15,800
FOR MORE DETAILS, BUT THEN WE

4015
02:21:15,800 --> 02:21:17,680
CAN USE THIS TO PROPOSE NEW

4016
02:21:17,680 --> 02:21:18,160
EXPERIMENTS.

4017
02:21:18,160 --> 02:21:20,360
SO HERE ARE SPECIFIC NEURONS IN

4018
02:21:20,360 --> 02:21:22,360
THIS CASE A NEURON WHICH OUGHT

4019
02:21:22,360 --> 02:21:27,040
TO BE QUITE SENSITIVE TO VISUAL

4020
02:21:27,040 --> 02:21:28,160
LOOMING, SHOULD BE QUITE SENSE

4021
02:21:28,160 --> 02:21:29,600
TOIF TO OBJECT MOTION BY

4022
02:21:29,600 --> 02:21:31,400
PROPERTIES OF ITS INPUT AND HERE

4023
02:21:31,400 --> 02:21:33,800
IS A NEURON THAT INTEGRATES A

4024
02:21:33,800 --> 02:21:35,240
LOOMING SENSITIVE PATHWAY AND

4025
02:21:35,240 --> 02:21:37,120
ONE FROM A SMALL OBJECT PATHWAY,

4026
02:21:37,120 --> 02:21:39,080
HOWEVER IT INTEGRATES FROM THE

4027
02:21:39,080 --> 02:21:41,080
FASTER NEURONS FROM EACH

4028
02:21:41,080 --> 02:21:42,400
PATHWAY, INTERESTING HYPOTHESIS

4029
02:21:42,400 --> 02:21:42,600
THERE.

4030
02:21:42,600 --> 02:21:44,800
WE CAN SEE THIS CONNECTOME

4031
02:21:44,800 --> 02:21:46,080
ANALYSIS QUICKLY FEEDS BACK TO

4032
02:21:46,080 --> 02:21:47,480
THE NEXT ROUND OF EXPERIMENTS WE

4033
02:21:47,480 --> 02:21:48,160
WOULD WANTED TO DO.

4034
02:21:48,160 --> 02:21:50,480
TO QUICKLY SUMMARIZE AS I'M

4035
02:21:50,480 --> 02:21:51,760
RUNNING OUT OF TIME, WE'VE BEEN

4036
02:21:51,760 --> 02:21:52,880
LOOKING ALTHOUGH VISUAL

4037
02:21:52,880 --> 02:21:54,200
PROJECTIONS IN THE FLY BRAIRNGS

4038
02:21:54,200 --> 02:21:56,080
DOZENS OF PARALLEL PATHWAYS THAT

4039
02:21:56,080 --> 02:22:01,000
GO INTO THE CENTRAL BRAIN, BEING

4040
02:22:01,000 --> 02:22:03,080
ENCODES DISTINCT VISUAL

4041
02:22:03,080 --> 02:22:03,360
FEATURES.

4042
02:22:03,360 --> 02:22:04,840
WE WERE ABLE TO READ OUT SOME

4043
02:22:04,840 --> 02:22:06,160
SPATIAL INFORMATION EVEN THOUGH

4044
02:22:06,160 --> 02:22:08,120
IT'S COARSER THAN WHAT YOU FIND

4045
02:22:08,120 --> 02:22:10,760
IN THE RETINOTOPIC FIELDS AND

4046
02:22:10,760 --> 02:22:15,360
ACROSS GLOMERULI WE FIND THAT

4047
02:22:15,360 --> 02:22:17,120
MORE SIMILAR ENCODING NEURONS

4048
02:22:17,120 --> 02:22:20,280
HAVE GLOMERULI THAT ARE CLOWER

4049
02:22:20,280 --> 02:22:21,920
TO EACH OTHER AND WE REALLY FIND

4050
02:22:21,920 --> 02:22:23,040
THERE'S ORGANIZATION EVERYWHERE,

4051
02:22:23,040 --> 02:22:24,560
NOTHING IS RANDOM OF THE LAST

4052
02:22:24,560 --> 02:22:25,960
POINT I LIKE TO LEAVE PEOPLE

4053
02:22:25,960 --> 02:22:27,840
WITH IS WHAT THIS HAS TAUGHT US

4054
02:22:27,840 --> 02:22:30,040
IS THESE PATHWAYS FOR VISUALLY

4055
02:22:30,040 --> 02:22:33,400
GUIDED BEHAVIORS ARE DEEPER THAN

4056
02:22:33,400 --> 02:22:37,120
PEOPLE EXPECTED, EVEN IN SIMPLE

4057
02:22:37,120 --> 02:22:38,640
FLY BRAIN, BUT WE HAVE ALL THE

4058
02:22:38,640 --> 02:22:41,960
TOOLS AND MORE CONNECTOMES

4059
02:22:41,960 --> 02:22:44,920
ONLINE TOMG CONGRESS UP TO HELP

4060
02:22:44,920 --> 02:22:47,320
US MAP THESE PATHWAYS WHICH IS

4061
02:22:47,320 --> 02:22:49,480
CONVERTED INTO BEHAVIOR WHICH IS

4062
02:22:49,480 --> 02:22:51,080
A TOPIC I'M EXCITED TO TALK

4063
02:22:51,080 --> 02:22:53,320
ABOUT AND WHAT I DO WITH THIS

4064
02:22:53,320 --> 02:22:54,360
AMAZING GROUP OF PEOPLE.

4065
02:22:54,360 --> 02:22:55,320
THANK YOU VERY MUCH FOR YOUR

4066
02:22:55,320 --> 02:22:56,760
TIEMENT, I LOOK FORWARD TO

4067
02:22:56,760 --> 02:22:58,160
THE -- FOR YOUR TIME, I LOOK

4068
02:22:58,160 --> 02:22:59,520
FORWARD TO THE DISCUSSION.

4069
02:22:59,520 --> 02:23:01,120
>> GOOD AFTERNOON.

4070
02:23:01,120 --> 02:23:03,760
SYNAPSES ARE THE HALLMARK OF THE

4071
02:23:03,760 --> 02:23:07,960
BRAIN AND 95 PERCENT OF

4072
02:23:07,960 --> 02:23:09,440
MAMMALIAN BRAIN SYNAPSES ARE

4073
02:23:09,440 --> 02:23:11,000
EXCITATORY AND IT'S RECENTLY

4074
02:23:11,000 --> 02:23:12,760
BECOME APPARENT THAT THERE'S A

4075
02:23:12,760 --> 02:23:14,720
VAST DIVERSITY OF EXCITATORY

4076
02:23:14,720 --> 02:23:16,600
SYNAPSE TYPE THAT DIFFER IN

4077
02:23:16,600 --> 02:23:17,680
THEIR MOLECULAR COMPOSITION.

4078
02:23:17,680 --> 02:23:19,080
THIS SYNAPSE DIVERSITY IS

4079
02:23:19,080 --> 02:23:22,240
DESCRIBED BY THE WORD SYNAPTOME

4080
02:23:22,240 --> 02:23:24,240
AND IMPORTANTLY THERE'S A

4081
02:23:24,240 --> 02:23:25,760
MOLECULAR LOGIC OF THE SYNAPSE

4082
02:23:25,760 --> 02:23:27,880
DIVERSITY AS SHOWN HERE WHERE

4083
02:23:27,880 --> 02:23:30,040
GENES ENCODE OBVIOUSLY RNA AND

4084
02:23:30,040 --> 02:23:31,480
PROTEINS, WHICH IN TURN ARE

4085
02:23:31,480 --> 02:23:34,400
BUILDING BLOCKS FOR BLOCKS FOR

4086
02:23:34,400 --> 02:23:36,040
COMPLEXES AND THOSE ARE BUILDING

4087
02:23:36,040 --> 02:23:37,560
BLOCKS FOR SUPER-COMPLEXES AND

4088
02:23:37,560 --> 02:23:39,560
IT IS THE COMPLEX AND IS SUPER

4089
02:23:39,560 --> 02:23:41,560
COMPLEXES THAT ARE DISTRIBUTED

4090
02:23:41,560 --> 02:23:42,840
INTO SYNAPSE TO SAY GIVE THEM

4091
02:23:42,840 --> 02:23:44,720
THEIR DIFFERENT MOLECULAR

4092
02:23:44,720 --> 02:23:45,600
COMPOSITIONS, THESE ARE REALLY

4093
02:23:45,600 --> 02:23:51,720
THE BUILDING BLOCKS FOR THE SNAP

4094
02:23:51,720 --> 02:23:53,440
SYNAPTOME.

4095
02:23:53,440 --> 02:23:56,120
THEN SPATIAL AT THE CELLULAR

4096
02:23:56,120 --> 02:23:57,480
LEVEL, DIFFERENT TYPES OF

4097
02:23:57,480 --> 02:23:58,560
SYNAPSES ARE DISTRIBUTED AND

4098
02:23:58,560 --> 02:24:00,760
THOSE DIFFERENT CELL TYPES THEN

4099
02:24:00,760 --> 02:24:01,920
POPULATE DAIFNT PARTS OF THE

4100
02:24:01,920 --> 02:24:06,000
BRAIN TO GIVE AN OVERALL

4101
02:24:06,000 --> 02:24:09,160
BRAIN-WIDE SYN APPEAR TOME BRAIN

4102
02:24:09,160 --> 02:24:09,720
ARCHITECTURE.

4103
02:24:09,720 --> 02:24:12,760
METHODS FOR EXAMINE INDIVIDUAL

4104
02:24:12,760 --> 02:24:14,400
SYNAPSES IN MAMMALIAN BRAIN ON

4105
02:24:14,400 --> 02:24:16,400
BRAIN WIDE SCALE AS SHOWN IN THE

4106
02:24:16,400 --> 02:24:19,800
TOP HERE INVOLVE, INVOLVE

4107
02:24:19,800 --> 02:24:21,320
TARGETING FLUORESCENT PROTEINS

4108
02:24:21,320 --> 02:24:25,040
TO ENDOGENOUS MOLECULES,

4109
02:24:25,040 --> 02:24:26,600
DIFFERENT TYPES OF COME PLEKS,

4110
02:24:26,600 --> 02:24:28,320
BY EXAM ANYONING THEIR

4111
02:24:28,320 --> 02:24:32,480
DISTRIBUTION SYNAPSES USING

4112
02:24:32,480 --> 02:24:33,600
MICROSCOPY, FOR EVERY INDIVIDUAL

4113
02:24:33,600 --> 02:24:35,680
WE CAN QUANTIFY A VARIETY OF

4114
02:24:35,680 --> 02:24:36,320
PARAMETERS EXPRESSION OF THE

4115
02:24:36,320 --> 02:24:38,080
PROTEIN AND SIZE AND SHAPE

4116
02:24:38,080 --> 02:24:39,280
PARAMETERS USING MACHINE

4117
02:24:39,280 --> 02:24:41,360
LEARNING DATA FROM BILLIONS OF

4118
02:24:41,360 --> 02:24:43,680
SYNAPSES AND THEN GENERATE DATA

4119
02:24:43,680 --> 02:24:45,880
DRIVEN CATALOGS OF SYNAPSE TYPES

4120
02:24:45,880 --> 02:24:47,520
FROM TWO PROTEINS YOU CAN DEFINE

4121
02:24:47,520 --> 02:24:50,000
THREE SYNAPSE TYPES AND 37

4122
02:24:50,000 --> 02:24:52,200
SUBTYPES AND THEN MAP THEM

4123
02:24:52,200 --> 02:24:53,400
ACROSS THE BRAIN.

4124
02:24:53,400 --> 02:24:56,280
NOW, THESE SUBTYPES ARE

4125
02:24:56,280 --> 02:24:57,920
CLASSIFIED AS I'VE MENTIONED BY

4126
02:24:57,920 --> 02:24:58,920
THE MOLECULAR COMPOSITION AS

4127
02:24:58,920 --> 02:25:00,560
WELL AS THEIR SIZE AND SHAPE

4128
02:25:00,560 --> 02:25:01,240
PARAMETERS ON THE BOTTOM.

4129
02:25:01,240 --> 02:25:02,640
BUT WHEN YOU DO THAT USING A

4130
02:25:02,640 --> 02:25:03,840
DATA DRIVEN APPROACH, YOU HAVE

4131
02:25:03,840 --> 02:25:04,960
TO ASK YOURSELF THE QUESTION,

4132
02:25:04,960 --> 02:25:06,680
DOES IT ACTUALLY TELL YOU

4133
02:25:06,680 --> 02:25:07,600
ANYTHING INFORMATIVE WHEN YOU

4134
02:25:07,600 --> 02:25:10,080
HAVE SO MANY SUBTYPES BEING

4135
02:25:10,080 --> 02:25:10,440
GENERATED?

4136
02:25:10,440 --> 02:25:13,000
AS SHOWN HERE IN THE MOUSE

4137
02:25:13,000 --> 02:25:14,400
HIPPOCAMPUS, THOSE PANELS THAT

4138
02:25:14,400 --> 02:25:15,840
YOU SEE ARE FOR INDIVIDUAL

4139
02:25:15,840 --> 02:25:17,040
SUBTYPES AND IT'S QUITE CLEAR

4140
02:25:17,040 --> 02:25:20,120
THAT SOME SUBTYPES ARE ENRICHED

4141
02:25:20,120 --> 02:25:23,080
IN PRINCIPAL AREAS OF THE

4142
02:25:23,080 --> 02:25:24,200
HIPPOCAMPUS, SOME ENRICHED

4143
02:25:24,200 --> 02:25:27,800
PARTICULARLY IN CA1, 2, CA3, AND

4144
02:25:27,800 --> 02:25:29,640
IN THE BOTTOM TWO PANELS YOU CAN

4145
02:25:29,640 --> 02:25:32,280
SEE THERE'S EVEN ARCHITECTURE

4146
02:25:32,280 --> 02:25:34,680
WITHIN SUB REGIONS OF THE BRAIN,

4147
02:25:34,680 --> 02:25:36,560
SUBTYPE 13 ON THE BOTTOM LEFT

4148
02:25:36,560 --> 02:25:39,480
GOES FROM STRONG WEAK ACROSS THE

4149
02:25:39,480 --> 02:25:42,720
CA1 STRATUM RA DIOTOM AND 24

4150
02:25:42,720 --> 02:25:45,640
DOES THE OPPOSITE OF THAT.

4151
02:25:45,640 --> 02:25:47,160
NOW, THESE MAPS THAT YOU SEE

4152
02:25:47,160 --> 02:25:50,320
ACROSS THE TOP SHOW YOU IN EACH

4153
02:25:50,320 --> 02:25:53,080
ONE OF THE PIXELS HERE THAT

4154
02:25:53,080 --> 02:25:55,280
THERE ARE THE COLOR CODE FOR 37

4155
02:25:55,280 --> 02:25:56,360
DIFFERENT SUBTYPES AND YOU'RE

4156
02:25:56,360 --> 02:25:58,240
SEEING THE MAIN ONE OR THE

4157
02:25:58,240 --> 02:25:59,760
DOMINANT SUBTYPE AND IT'S CLEAR

4158
02:25:59,760 --> 02:26:06,440
THERE IS THIS EXQUISITE RSZ SYN

4159
02:26:06,440 --> 02:26:08,560
APPEARTOME ARCHITECTURE.

4160
02:26:08,560 --> 02:26:09,640
LOWER, THERE'S AN INTERESTING

4161
02:26:09,640 --> 02:26:10,240
MAP.

4162
02:26:10,240 --> 02:26:12,480
WHAT WE'RE QUANTIFYING HERE IS

4163
02:26:12,480 --> 02:26:13,480
SYNAPSE TYPE DIVERSITY.

4164
02:26:13,480 --> 02:26:16,080
WE FIND 9 HIGHEST SYNAPSE TYPE

4165
02:26:16,080 --> 02:26:17,200
DIVERSITY IS WITHIN THOSE AREAS

4166
02:26:17,200 --> 02:26:18,920
OF HIGHER COGNITIVE FUNCTIONS,

4167
02:26:18,920 --> 02:26:21,480
CORTEX AND HIPPOCAMPUS AND MORE

4168
02:26:21,480 --> 02:26:22,320
BASAL STRUCTURES OF THE BRAIN

4169
02:26:22,320 --> 02:26:24,200
HAVE A MUCH LOWER SYNAPSE

4170
02:26:24,200 --> 02:26:26,360
DIVERSITY AND IF YOU LOOK INTO

4171
02:26:26,360 --> 02:26:29,240
THE DIFFERENT SUB REGIONS OF THE

4172
02:26:29,240 --> 02:26:30,560
NEOCORTEX FOR EXAMPLE AS SHOWN

4173
02:26:30,560 --> 02:26:32,560
HERE, THERE ARE THREE PAIRS OF

4174
02:26:32,560 --> 02:26:36,360
BOXES FOR SOMATOSENSORY,

4175
02:26:36,360 --> 02:26:37,240
VISUALIZATION AREAS AND EACH

4176
02:26:37,240 --> 02:26:39,840
AREA OF THE CORTEX HAS A VERY

4177
02:26:39,840 --> 02:26:41,160
DISTINCT LAYERING PAFT OF

4178
02:26:41,160 --> 02:26:46,640
DIFFERENT TYPES OF SYNAPSES,

4179
02:26:46,640 --> 02:26:47,520
TECTONIC MAP.

4180
02:26:47,520 --> 02:26:49,280
I'M NOT GOING TO SHOW YOU IN

4181
02:26:49,280 --> 02:26:51,000
THIS PLENGS HOW THESE

4182
02:26:51,000 --> 02:26:52,520
DIFFERENTIAL DISTRIBUTIONS

4183
02:26:52,520 --> 02:26:54,400
CORRELATE WITH PHYSIOLOGICAL

4184
02:26:54,400 --> 02:26:58,240
FUNCTIONS AND STRUCTURAL

4185
02:26:58,240 --> 02:26:59,120
CONNECTOMES, YOU CAN READ ON

4186
02:26:59,120 --> 02:27:01,520
THAT SUBJECT.

4187
02:27:01,520 --> 02:27:03,800
BUT SOME OF THE SURPRISE HAS

4188
02:27:03,800 --> 02:27:09,720
COME FROM SYAPTOME -- SYNAPTOME

4189
02:27:09,720 --> 02:27:11,920
MAPPING, HIGHLY DIVERSE, TWO

4190
02:27:11,920 --> 02:27:13,760
PROTEINS CAN GIVE 37 SUBTYPES,

4191
02:27:13,760 --> 02:27:15,200
TEN PROTEINS COULD GIVE YOU TONE

4192
02:27:15,200 --> 02:27:16,400
THE ELEVEN SUBTYPES WHICH IS

4193
02:27:16,400 --> 02:27:17,480
ACTUALLY ABOUT THE NUMBER OF

4194
02:27:17,480 --> 02:27:18,600
SYNAPSE PS IN THE MOUSE BRAIN

4195
02:27:18,600 --> 02:27:20,440
BUT IN FACT THERE'S MORE THAN

4196
02:27:20,440 --> 02:27:22,280
1,000 POSTSYNAPTIC PROTEINS AND

4197
02:27:22,280 --> 02:27:23,920
POTENTIALLY INFINITE NUMBER OF

4198
02:27:23,920 --> 02:27:25,480
SYNAPSE TYPES AND SUBTYPES,

4199
02:27:25,480 --> 02:27:26,560
CLEARLY THERE'S A LOT OF

4200
02:27:26,560 --> 02:27:27,880
CONSTRAINT FOR ALL SORTS OF

4201
02:27:27,880 --> 02:27:29,400
REASONS WHICH I WON'T DID INTO

4202
02:27:29,400 --> 02:27:29,720
HERE.

4203
02:27:29,720 --> 02:27:32,160
THE SECOND SURPRISE IS THAT THE

4204
02:27:32,160 --> 02:27:33,680
SYNAPTOME IS ORGANIZED DUE TO

4205
02:27:33,680 --> 02:27:35,960
SPATIAL OR SYNAPTOME

4206
02:27:35,960 --> 02:27:37,080
ARCHITECTURE AND INDIVIDUAL

4207
02:27:37,080 --> 02:27:38,200
DENDRITES YOU CAN SEE DIFFERENT

4208
02:27:38,200 --> 02:27:40,600
TYPES OF SYNAPSES ADJACENT TO

4209
02:27:40,600 --> 02:27:41,800
ONE ANOTHER AND DISTRIBUTED

4210
02:27:41,800 --> 02:27:43,320
ALONG THE LENGTH FLT DENDRITES

4211
02:27:43,320 --> 02:27:45,640
WITHIN THE NEURONAL DENDRITE

4212
02:27:45,640 --> 02:27:47,640
TREE, CELL TYPE DIFFERENCES

4213
02:27:47,640 --> 02:27:48,920
REGION IN THE WHOLE BRAIN

4214
02:27:48,920 --> 02:27:50,040
DIFFERENCES AS WELL.

4215
02:27:50,040 --> 02:27:51,440
BUT THEN WE WANTED TO TAKE THIS

4216
02:27:51,440 --> 02:27:53,160
TECHNOLOGY ONWARDS AND MAP

4217
02:27:53,160 --> 02:27:54,480
ACROSS THE WHOLE BRAIN OF THE

4218
02:27:54,480 --> 02:27:56,360
MOUSE FROM BIRTH UNTIL 18 MONTHS

4219
02:27:56,360 --> 02:27:57,880
TO GENERAL RAIPT THE FIRST BRAIN

4220
02:27:57,880 --> 02:27:59,680
WIDE QUANTIFICATION OF SYNAPSE

4221
02:27:59,680 --> 02:28:01,440
AND SYNAPSE TYPES ACROSS THE

4222
02:28:01,440 --> 02:28:03,720
LIFE SPAN OF ANY SPECIES.

4223
02:28:03,720 --> 02:28:05,760
AND IN EVERY BRAIN REGION AND

4224
02:28:05,760 --> 02:28:08,120
SUB REGION, THERE IS A

4225
02:28:08,120 --> 02:28:11,480
TRAJECTORY WITH AGE AND SYNAPSE

4226
02:28:11,480 --> 02:28:12,360
NUMBER, SYNAPSE PROTEIN

4227
02:28:12,360 --> 02:28:13,880
COMPOSITION, SIZE AND SHAPE AND

4228
02:28:13,880 --> 02:28:15,520
SYNAPSE DIVERSITY ARE

4229
02:28:15,520 --> 02:28:16,640
CONTINUOUSLY CHANGING.

4230
02:28:16,640 --> 02:28:18,480
BRAIN SYNAPTOME AND SNAP TONE

4231
02:28:18,480 --> 02:28:20,040
ARCHITECTURE IS CONTINUOUSLY

4232
02:28:20,040 --> 02:28:21,760
CHANGING ACROSS THE LIFE SPAN

4233
02:28:21,760 --> 02:28:23,400
BUT AT DIFFERENT RATES.

4234
02:28:23,400 --> 02:28:25,040
I'LL SHOW YOU A COUPLE FEATURES

4235
02:28:25,040 --> 02:28:25,800
OF THIS.

4236
02:28:25,800 --> 02:28:28,800
THESE ARE MAPS OF MOUSE BRAIN.

4237
02:28:28,800 --> 02:28:28,960
THE.

4238
02:28:28,960 --> 02:28:31,120
AT THE TOP PANEL HERE THEY'RE AT

4239
02:28:31,120 --> 02:28:32,640
ONE WEEK INTERVALS UP THROUGH

4240
02:28:32,640 --> 02:28:34,160
THREE WEEKS ACROSS TO THE FAR

4241
02:28:34,160 --> 02:28:35,480
RIGHT THERE AND THE BOTTOM SET

4242
02:28:35,480 --> 02:28:37,200
OF PANELS THEN BECOME ONE, TWO

4243
02:28:37,200 --> 02:28:38,840
AND THREE MONTHS OF AGE BHAVMENT

4244
02:28:38,840 --> 02:28:40,960
WE'RE LOOKING AT.

4245
02:28:40,960 --> 02:28:42,360
WHAT WE'RE LOOKING AT HERE IS

4246
02:28:42,360 --> 02:28:43,920
THE DIVERSITY, BLUE BEING LOW,

4247
02:28:43,920 --> 02:28:45,120
RED BEING HIGH.

4248
02:28:45,120 --> 02:28:46,760
QUITE OBVIOUSLY IN THE FIRST

4249
02:28:46,760 --> 02:28:48,200
COUPLE WEEKS SYNAPSE DIVERSITY

4250
02:28:48,200 --> 02:28:49,640
IS REALLY VERY LOW BUT AS YOU

4251
02:28:49,640 --> 02:28:52,320
CAN SEE IT BEGINS TO INCREASE

4252
02:28:52,320 --> 02:28:53,440
QUITE DRAMATICALLY AND THE

4253
02:28:53,440 --> 02:28:55,520
IMPORTANT THING HERE IS NOT ONLY

4254
02:28:55,520 --> 02:28:57,160
THAT IT IS INCREASING SYNAPSE

4255
02:28:57,160 --> 02:28:59,120
DIVERSITY AS THESE NEW TYPES OF

4256
02:28:59,120 --> 02:29:00,240
SYNAPSES POPULATE IN THE BRAIN

4257
02:29:00,240 --> 02:29:02,080
BUT IT IS THAT THEY GIVE EACH

4258
02:29:02,080 --> 02:29:05,720
AREA OF THE BRAIN ITS DISTINCT

4259
02:29:05,720 --> 02:29:07,000
SYNAPTOME COMPOSITION AND

4260
02:29:07,000 --> 02:29:09,520
SYNAPTOME ARCHITECTURE.

4261
02:29:09,520 --> 02:29:10,960
AND JUST ON THE OTHER END OF THE

4262
02:29:10,960 --> 02:29:12,480
LIFE SPAN, WE'LL HAVE A LOOK AT

4263
02:29:12,480 --> 02:29:15,120
AGING HERE, I'LL JUST SHOW YOU A

4264
02:29:15,120 --> 02:29:15,880
COUPLE THINGS.

4265
02:29:15,880 --> 02:29:17,960
IT'S WELL-KNOWN FROM STUDIES

4266
02:29:17,960 --> 02:29:19,200
FOIBLTION ODD PARTICULAR KEY

4267
02:29:19,200 --> 02:29:20,800
AREAS OF THE MAMMALIAN BRAIN

4268
02:29:20,800 --> 02:29:22,560
THAT THERE'S SYNAPSE LOSS BUT

4269
02:29:22,560 --> 02:29:24,760
THIS SHOWS YOU FOR THESE TWO

4270
02:29:24,760 --> 02:29:27,160
MARKERS HERE, THE REDUCTION IN

4271
02:29:27,160 --> 02:29:29,240
SYNAPSE NUMBER THAT OCCURS FOR

4272
02:29:29,240 --> 02:29:30,680
THOSE IN THESE DIFFERENT BRAIN

4273
02:29:30,680 --> 02:29:33,480
AREAS THAT WE'VE EXAMINED.

4274
02:29:33,480 --> 02:29:34,840
OVERALL THERE'S A GENERAL LOSS.

4275
02:29:34,840 --> 02:29:37,120
BUT WHEN YOU NOW LOOK AT THE

4276
02:29:37,120 --> 02:29:38,960
SYNAPSE SUBTYPES AND I'M JUST

4277
02:29:38,960 --> 02:29:40,960
SHOWING YOU TWO HEAT MAPS HERE

4278
02:29:40,960 --> 02:29:43,280
FOR FOUR SUBTYPES, LET ME ORIENT

4279
02:29:43,280 --> 02:29:45,360
YOU ON THESE HEAT MAPS.

4280
02:29:45,360 --> 02:29:48,240
THE VERTICAL AXIS IS ABOUT 100

4281
02:29:48,240 --> 02:29:50,360
OR SO DIFFERENT BRAIN REGIONS

4282
02:29:50,360 --> 02:29:51,800
AND HORIZONTALLY WE'RE LOOKING

4283
02:29:51,800 --> 02:29:54,200
AT THEIR LIFE SPAN TRAJECTORY

4284
02:29:54,200 --> 02:29:58,480
FROM THE FIRST DEAF LIFE ON THE

4285
02:29:58,480 --> 02:30:01,040
LEFT DISPOF 08 MONTHS ON THE

4286
02:30:01,040 --> 02:30:01,320
RIGHT.

4287
02:30:01,320 --> 02:30:03,000
TWO HEAT MAPS ON THE LEFT IN

4288
02:30:03,000 --> 02:30:04,520
GENERAL THE YELLOW WHICH IS THE

4289
02:30:04,520 --> 02:30:06,120
HIGHEST DENSITY FOR THESE

4290
02:30:06,120 --> 02:30:07,880
PARTICULAR SUBTYPES IS GENERALLY

4291
02:30:07,880 --> 02:30:09,320
PRETTY HIGH IN ABOUT THE SECOND

4292
02:30:09,320 --> 02:30:10,880
AND THIRD COLUMNS FROM THAT AND

4293
02:30:10,880 --> 02:30:12,720
THEN THEY'RE GENERALLY BECOME

4294
02:30:12,720 --> 02:30:14,120
REDUCED AS YOU GET OLDER.

4295
02:30:14,120 --> 02:30:16,000
THESE ARE EAJ SENSITIVE, THESE

4296
02:30:16,000 --> 02:30:17,440
ARE SUBTYPES THAT PEAK EARLY IN

4297
02:30:17,440 --> 02:30:19,080
LIFE AND GENERALLY BECOME LOST

4298
02:30:19,080 --> 02:30:21,040
A'S THE ANIMAL GETS OLDER.

4299
02:30:21,040 --> 02:30:21,840
BUT ON THE OTHER HAND THESE

4300
02:30:21,840 --> 02:30:23,920
SECOND THE LAST TWO THIRD AND

4301
02:30:23,920 --> 02:30:25,200
FOURTH HEAT MAPS YOU CAN SEE ARE

4302
02:30:25,200 --> 02:30:26,200
THE OPPOSITE OF THAT.

4303
02:30:26,200 --> 02:30:28,400
THESE ARE EAJ RESILIENT

4304
02:30:28,400 --> 02:30:30,840
SYNAPSES, THESE ARE SUBTYPES OF

4305
02:30:30,840 --> 02:30:32,800
SYNAPSES THAT DEFY THE AGING

4306
02:30:32,800 --> 02:30:34,720
PROCESS AND REMAIN ROBUSTING AND

4307
02:30:34,720 --> 02:30:37,840
ARE NOT LOST AS YOU GET OLDER.

4308
02:30:37,840 --> 02:30:39,040
SO CLEARLY A VERY INTERESTING

4309
02:30:39,040 --> 02:30:40,440
QUESTION IS TO ASK WHAT'S

4310
02:30:40,440 --> 02:30:42,080
DIFFERENT ABOUT THOSE SYNAPSES?

4311
02:30:42,080 --> 02:30:43,640
I'LL COME BACK TO THAT LATER ON

4312
02:30:43,640 --> 02:30:45,120
AND SHOW YOU SOMETHING QUITE

4313
02:30:45,120 --> 02:30:46,320
INTERESTING ON THAT SUBJECT.

4314
02:30:46,320 --> 02:30:47,960
BUT I WOULD JUST LIKE TO

4315
02:30:47,960 --> 02:30:49,600
SPECULATE FOR A MOMENT, FROM

4316
02:30:49,600 --> 02:30:51,680
HUMAN STUDIES IN PARTICULAR,

4317
02:30:51,680 --> 02:30:53,440
THERE'S BEEN A VERY CLEAR

4318
02:30:53,440 --> 02:30:54,880
DICHOTOMY AND COGNITIVE FUNCTION

4319
02:30:54,880 --> 02:30:56,960
WITH AGING WHERE THERE IS A

4320
02:30:56,960 --> 02:30:58,840
REDUCTION AS SHOWN IN THESE

4321
02:30:58,840 --> 02:30:59,800
LEFT-HAND GRAPHS WITH AGING

4322
02:30:59,800 --> 02:31:01,680
HUMANS OF WHAT'S KNOWN AS FLUID

4323
02:31:01,680 --> 02:31:03,400
COGNITION WHICH ESSENTIALLY IS

4324
02:31:03,400 --> 02:31:05,400
PROCESSING SPEED, WORKING MEARM,

4325
02:31:05,400 --> 02:31:06,480
ATTENTION, EXECUTIVE FUNCTION,

4326
02:31:06,480 --> 02:31:08,440
AND LEARNING EFFICIENCY.

4327
02:31:08,440 --> 02:31:09,640
BUT THAT IS IN CONTRAST TO

4328
02:31:09,640 --> 02:31:11,920
ANOTHER TYPE OF COGNITION KNOWN

4329
02:31:11,920 --> 02:31:13,560
AS CRYSTALLIZED COGNITION WHICH

4330
02:31:13,560 --> 02:31:15,560
IS STABLE WITH AGING, THAT'S

4331
02:31:15,560 --> 02:31:17,520
ACQUIRED KNOWLEDGE AND REALLY

4332
02:31:17,520 --> 02:31:20,320
CORE CAPACITIES SUCH AS LANGUAGE

4333
02:31:20,320 --> 02:31:22,120
AND IT'S AN INTERESTING THING TO

4334
02:31:22,120 --> 02:31:23,680
SPECULATE AND PERHAPS SOMETHING

4335
02:31:23,680 --> 02:31:25,200
WE COULD ULTIMATELY TEST OF

4336
02:31:25,200 --> 02:31:26,360
THESE DIFFERENT SYNAPSES MIGHT

4337
02:31:26,360 --> 02:31:27,920
BE ASSIGNED TO THESE DIFFERENT

4338
02:31:27,920 --> 02:31:28,920
TYPES OF FUNCTIONS.

4339
02:31:28,920 --> 02:31:29,960
I'M GOING TO CHANGE SUBJECTS

4340
02:31:29,960 --> 02:31:31,200
HERE BECAUSE WHAT I'VE SHOWN YOU

4341
02:31:31,200 --> 02:31:33,720
IS THE MOLECULAR COMPOSITION,

4342
02:31:33,720 --> 02:31:35,360
STALT I CAN COMPOSITION, BUT

4343
02:31:35,360 --> 02:31:37,080
PROTEINS HAVE A LIFETIME.

4344
02:31:37,080 --> 02:31:38,520
THEY TURN OVER.

4345
02:31:38,520 --> 02:31:40,680
SO PROTEINS WITH LONG LIFETIMES

4346
02:31:40,680 --> 02:31:45,080
HAVE A VERY RAPID TURNOVER RATE.

4347
02:31:45,080 --> 02:31:47,680
SORRY, JUST BENEATH THAT, LONG

4348
02:31:47,680 --> 02:31:49,120
LIFETIME, SO SLOW PROTEIN

4349
02:31:49,120 --> 02:31:50,080
TURNOVER RATE AND THAT'S AN

4350
02:31:50,080 --> 02:31:51,320
IMPORTANT THING BECAUSE THAT

4351
02:31:51,320 --> 02:31:53,400
MEANS THERE'S A SLOW REMOVAL OF

4352
02:31:53,400 --> 02:31:55,920
MODIFIED OR DAMAGED PROTEINS AND

4353
02:31:55,920 --> 02:31:58,680
SLOW PROTEOSTASIS MEANS SLOW

4354
02:31:58,680 --> 02:32:00,400
HOMOEOSTASIS AND SLOW

4355
02:32:00,400 --> 02:32:00,720
ADAPTATION.

4356
02:32:00,720 --> 02:32:02,600
SO THE QUESTION IS, DO SYNAPSES

4357
02:32:02,600 --> 02:32:04,360
HAVE DIFFERENT PROTEIN

4358
02:32:04,360 --> 02:32:05,520
LIFETIMES?

4359
02:32:05,520 --> 02:32:08,320
NOW, THE LIFETIME OF ENDOGENOUS

4360
02:32:08,320 --> 02:32:09,720
SYNAPTIC PROTEINS HAS NOT BEEN

4361
02:32:09,720 --> 02:32:11,440
STUDIED AT SINGLE SYNAPSE

4362
02:32:11,440 --> 02:32:12,760
RESOLUTION AND CERTAINLY NOT AT

4363
02:32:12,760 --> 02:32:15,520
A BRAIN WIDE SCIEL WE DEVELOPED

4364
02:32:15,520 --> 02:32:17,440
A METHAMPHETAMINE ODD TO DO THAT

4365
02:32:17,440 --> 02:32:19,560
WHICH IS REPORTED IN THIS PAPER

4366
02:32:19,560 --> 02:32:22,200
ON NILE ARC IEFDZ LED BY Ph.D.

4367
02:32:22,200 --> 02:32:23,720
STUDENT AND WHAT WE'VE USED HERE

4368
02:32:23,720 --> 02:32:27,760
IS THE PALO TAG ATTACHED TO THE

4369
02:32:27,760 --> 02:32:29,080
PSD95 PROTEIN AND ON THE LEFT

4370
02:32:29,080 --> 02:32:31,400
YOU CAN SEE A SCHEMATIC

4371
02:32:31,400 --> 02:32:32,640
THREE-DIMENSIONAL STRUCTURE OF

4372
02:32:32,640 --> 02:32:34,240
THE HALO PHAGO WHICH IS

4373
02:32:34,240 --> 02:32:36,200
ESSENTIALLY CONTAINS -- HALO TAG

4374
02:32:36,200 --> 02:32:37,400
WHICH ESSENTIALLY CONTAINS A

4375
02:32:37,400 --> 02:32:38,920
BINDING POCKET INTO CL A SMALL

4376
02:32:38,920 --> 02:32:40,600
MOLECULE FORMS A COVALENT BOND

4377
02:32:40,600 --> 02:32:42,640
AND THUS PERMANENTLY BINDING TO

4378
02:32:42,640 --> 02:32:45,280
THE HALO TAG PROTEIN DOMAIN.

4379
02:32:45,280 --> 02:32:46,600
THE BEAUTY OF THIS IS THAT YOU

4380
02:32:46,600 --> 02:32:51,280
CAN COUPLE TO THAT HALO TAG

4381
02:32:51,280 --> 02:32:53,600
LIGAND ANYTHING YOU LIKE SUCH

4382
02:32:53,600 --> 02:32:55,760
THAT IF YOU WERE TO INJECT THIS

4383
02:32:55,760 --> 02:32:59,720
INTO THE MOUSE AND LABEL PS95

4384
02:32:59,720 --> 02:33:02,560
WITH HALO TAG ON IT, YOU'LL GET

4385
02:33:02,560 --> 02:33:04,080
IRREVERSIBLE LAG EXPLENGT SEE

4386
02:33:04,080 --> 02:33:06,080
THE DYNAMICS AS IT'S LOST

4387
02:33:06,080 --> 02:33:07,040
THROUGHOUT TIME.

4388
02:33:07,040 --> 02:33:09,000
HERE IS A SCREMATIC PRESENTATION

4389
02:33:09,000 --> 02:33:10,360
WHAT YOU MIGHT LOOK FOR.

4390
02:33:10,360 --> 02:33:10,600
TWO ROSE.

4391
02:33:10,600 --> 02:33:13,040
TOP ONE, TYPE OF SYNAPSE WHERE

4392
02:33:13,040 --> 02:33:15,000
PROTEINS HAVE BEEN A SHORT

4393
02:33:15,000 --> 02:33:16,320
LIFETIME AND ONE AT THE BOTTOM

4394
02:33:16,320 --> 02:33:18,520
IS A LONG PROTEIN LIFETIME

4395
02:33:18,520 --> 02:33:18,760
SYNAPSE.

4396
02:33:18,760 --> 02:33:22,040
THEY CONTAIN PSD95 IN THE

4397
02:33:22,040 --> 02:33:24,960
POSTSYNAPTIC REGION OF THE

4398
02:33:24,960 --> 02:33:25,280
SYNAPSE.

4399
02:33:25,280 --> 02:33:29,480
WHERE THE RED BAR SAYS HALO

4400
02:33:29,480 --> 02:33:32,200
INJECTION, ATTACHED TO HALO, WE

4401
02:33:32,200 --> 02:33:33,520
INJECT THE MICE AND CAN LABEL

4402
02:33:33,520 --> 02:33:34,520
ALL THE PROTEIN.

4403
02:33:34,520 --> 02:33:36,160
THE TOP SYNAPSE TURNS OVER THE

4404
02:33:36,160 --> 02:33:37,680
PROTEIN VERY QUICKLY, SYNAPSE

4405
02:33:37,680 --> 02:33:39,320
PROTEIN HAS A SHORT LIFETIME SO

4406
02:33:39,320 --> 02:33:41,280
IT DISAPPEARS RAPIDLY UNLIKE

4407
02:33:41,280 --> 02:33:42,600
THAT AT THE BOTTOM WHERE IT HAS

4408
02:33:42,600 --> 02:33:44,360
A SLOW PROTEIN TURNOVER AND A

4409
02:33:44,360 --> 02:33:45,600
LONG PROTEIN LIFETIME WHERE IT

4410
02:33:45,600 --> 02:33:47,400
IS RETAINED SO THEREFORE SIMPLY

4411
02:33:47,400 --> 02:33:50,160
BY INJECTING THE MICE WITH THIS

4412
02:33:50,160 --> 02:33:54,520
LIE LIGAND AND USUALLY -- AND

4413
02:33:54,520 --> 02:33:55,920
USING PIPELINE MAPPING, WE CAN

4414
02:33:55,920 --> 02:33:58,120
DO SANG HE WILL RESOURCE MAP OF

4415
02:33:58,120 --> 02:33:59,440
PROTEIN TURNOVER IN THE MOUSE

4416
02:33:59,440 --> 02:33:59,960
BRAIN.

4417
02:33:59,960 --> 02:34:01,640
I'LL SHOW YOU A COUPLE CLOSEUPS

4418
02:34:01,640 --> 02:34:02,960
THAT ILLUSTRATE FOR YOU THAT THE

4419
02:34:02,960 --> 02:34:05,000
REASONS ARE TURNING OVER IN

4420
02:34:05,000 --> 02:34:05,280
SYNAPSES.

4421
02:34:05,280 --> 02:34:07,320
ON THE TOP LEFT IF YOU NEED A

4422
02:34:07,320 --> 02:34:09,160
CLOSE-UP OF THE MOTOR CORTEX FOR

4423
02:34:09,160 --> 02:34:10,720
ANIMALS THAT HAVE BEEN INJECTED

4424
02:34:10,720 --> 02:34:12,560
WITH ONE DYE ON DAY ZERO AND

4425
02:34:12,560 --> 02:34:14,760
THREE DAYS LATER WITH ANOTHER

4426
02:34:14,760 --> 02:34:16,480
DYE AND ONE BEING RED AND THE

4427
02:34:16,480 --> 02:34:18,000
OTHER GREEN AND HENCE YOU CAN

4428
02:34:18,000 --> 02:34:19,880
SEE THE MERGED SIGNAL AND THAT

4429
02:34:19,880 --> 02:34:21,400
MERGED SIGNAL TELLS YOU THAT THE

4430
02:34:21,400 --> 02:34:22,960
PROTEINS ARE TURNING OVER IN

4431
02:34:22,960 --> 02:34:24,840
THOSE SYNAPSES.

4432
02:34:24,840 --> 02:34:29,840
IN COLLABORATION WITH ANTHONY

4433
02:34:29,840 --> 02:34:32,360
HOLTMART'S GROUP IN GENEVA HE

4434
02:34:32,360 --> 02:34:35,080
IMAGED WITH LIVE MICE IN LAYER

4435
02:34:35,080 --> 02:34:36,840
TWO OF THE CORTEX THE TURNOVER

4436
02:34:36,840 --> 02:34:39,120
THE SYNAPTIC PROTEINS USING THE

4437
02:34:39,120 --> 02:34:41,320
HALO TAG OVER A PERIOD OF A

4438
02:34:41,320 --> 02:34:43,840
MONTH OR MORE AND HE COULD

4439
02:34:43,840 --> 02:34:45,600
INDIVIDUALLY SEE THE DENDRITIC

4440
02:34:45,600 --> 02:34:48,640
SPINES THERE AS SHOWN IN THE TOP

4441
02:34:48,640 --> 02:34:50,320
AND THE ILLUSTRATED AT THE

4442
02:34:50,320 --> 02:34:52,600
BOTTOM SET OF THREE PANELS

4443
02:34:52,600 --> 02:34:57,120
LABELED WITH HALO TAG AND THE

4444
02:34:57,120 --> 02:34:59,200
INDIVIDUAL SYNAPSES ON THESE

4445
02:34:59,200 --> 02:35:00,400
DENDRITES HAVE DIFFERENT

4446
02:35:00,400 --> 02:35:01,600
LIFETIME AS SHOWN ON THAT GRAPH

4447
02:35:01,600 --> 02:35:04,040
ON THE RIGHT, SOME SYNAPSES LOSE

4448
02:35:04,040 --> 02:35:05,920
THE PROTEIN OR HAVE A VERY SHORT

4449
02:35:05,920 --> 02:35:09,640
LIFETIME AND OTHERS HAVE A LONG

4450
02:35:09,640 --> 02:35:10,040
LIFETIME.

4451
02:35:10,040 --> 02:35:11,520
SO HERE ARE SOME EXAMPLES OF I

4452
02:35:11,520 --> 02:35:13,600
AM NOODGES THE BRAIN, EACH

4453
02:35:13,600 --> 02:35:15,680
COLUMN IS A PARTICULAR DAY AFTER

4454
02:35:15,680 --> 02:35:17,080
INJECTION, IF YOU LOOK AT THE

4455
02:35:17,080 --> 02:35:18,600
TOP AT THE WHOLE BRAIN YOU'LL

4456
02:35:18,600 --> 02:35:21,680
SEE VERY CHARACTERISTIC LABELING

4457
02:35:21,680 --> 02:35:23,200
OF 95 AT DAY ZERO.

4458
02:35:23,200 --> 02:35:24,600
BY DAY 14 YOU CAN SEE THAT

4459
02:35:24,600 --> 02:35:27,240
ESSENTIAL ALMOST ALL ALL THE --

4460
02:35:27,240 --> 02:35:28,680
IS GONE AND I MUST STOP AND

4461
02:35:28,680 --> 02:35:29,800
PAUSE FOR A SECOND BECAUSE I

4462
02:35:29,800 --> 02:35:31,760
THINK ITS TRULY ASTONISHING WHEN

4463
02:35:31,760 --> 02:35:33,280
YOU HAVE THIS AMAZE BEING SYN

4464
02:35:33,280 --> 02:35:36,160
APPEAR TOMORROW ARCHITECTURE.

4465
02:35:36,160 --> 02:35:37,600
BRAIN -- SYNAPTOME ARCHITECTURE

4466
02:35:37,600 --> 02:35:39,520
OF THE BRAIN, THAT IT'S BEING

4467
02:35:39,520 --> 02:35:40,960
REBUILT EVERY COUPLE WEEKS AND

4468
02:35:40,960 --> 02:35:43,000
THE BRAIN HAS THIS REMARKABLE

4469
02:35:43,000 --> 02:35:46,680
ABILITY TO DO THAT.

4470
02:35:46,680 --> 02:35:48,120
SOME OF THE SIGNAL REMAINS IT

4471
02:35:48,120 --> 02:35:49,600
SOME OF THESE AREAS AND SOME OF

4472
02:35:49,600 --> 02:35:52,440
THESE SYNAPSES HAVE A VERY LONG

4473
02:35:52,440 --> 02:35:53,040
LIFETIME.

4474
02:35:53,040 --> 02:35:54,520
HERE WE'VE MAPPED THE AVERAGE

4475
02:35:54,520 --> 02:35:55,640
HALF-LIFE SYNAPTIC PROTEINS IN

4476
02:35:55,640 --> 02:35:56,800
THESE DIFFERENT AREAS OF THE

4477
02:35:56,800 --> 02:35:59,000
BRAIN AND THEY DIFFER BY TENFOLD

4478
02:35:59,000 --> 02:36:00,560
IN THESE DIFFERENT REEXPWRONS

4479
02:36:00,560 --> 02:36:02,280
QUITE NOTICEABLY YOU'LL --

4480
02:36:02,280 --> 02:36:03,160
REEXPWRONS QUITE NOTICEABLY

4481
02:36:03,160 --> 02:36:04,920
YOU'LL SEE THE SUPER SUPERFICIAL

4482
02:36:04,920 --> 02:36:06,800
LAYERS OF THE CORTEX HAVE A VERY

4483
02:36:06,800 --> 02:36:08,200
SLOW TURNOVER OF PROTEIN AND

4484
02:36:08,200 --> 02:36:10,840
VERY LONG PROTEIN LIFETIME.

4485
02:36:10,840 --> 02:36:15,640
IF YOU LOOK WITHINS NEURONONTZ

4486
02:36:15,640 --> 02:36:19,240
CA LEE REGION YOU CAN SEE ON

4487
02:36:19,240 --> 02:36:21,760
THIS GRAPH ON THE Y AXIS LOOKING

4488
02:36:21,760 --> 02:36:23,080
AT THE ESSENTIAL PROTEIN

4489
02:36:23,080 --> 02:36:24,760
LIFETIME TO DISTAL DENDRITES TO

4490
02:36:24,760 --> 02:36:26,760
THE RIGHT YOU CAN SEE THERE'S AN

4491
02:36:26,760 --> 02:36:28,440
OVERALL GRADIENT THERE SUCH AS

4492
02:36:28,440 --> 02:36:30,040
MORE DISTAL SYNAPSES HAVE A

4493
02:36:30,040 --> 02:36:31,520
LONGER PROTEIN LIFETIME THAN

4494
02:36:31,520 --> 02:36:34,360
THOSE THAT ARE MORE PROXIMAL.

4495
02:36:34,360 --> 02:36:35,760
AND ONE OF THE QUESTIONS WE WANT

4496
02:36:35,760 --> 02:36:38,280
TO ASK IS WHETHER OR NOT THESE

4497
02:36:38,280 --> 02:36:39,920
COMPOSITIONAL SUBTYPES AND

4498
02:36:39,920 --> 02:36:42,360
THIEPS WE DEFINED USING THESE

4499
02:36:42,360 --> 02:36:44,520
GFP AND ORANGE LABELS ARE IN ANY

4500
02:36:44,520 --> 02:36:46,160
WAY RELATED TO THE PROTEIN

4501
02:36:46,160 --> 02:36:46,440
LIFETIMES.

4502
02:36:46,440 --> 02:36:48,800
COULD IT BE THAT SOME OF THESE

4503
02:36:48,800 --> 02:36:50,440
SUBTYPES HAVE PARTICULAR

4504
02:36:50,440 --> 02:36:51,960
COMPOSITIONS THAT HAVE DIFFERENT

4505
02:36:51,960 --> 02:36:52,440
LIFETIMES?

4506
02:36:52,440 --> 02:36:55,240
WE DID THIS BY CROSSING TO MAKE

4507
02:36:55,240 --> 02:36:58,160
A TRIPLE LABELED MOUSE WITH 95

4508
02:36:58,160 --> 02:37:00,400
SPAITION GFP AND ORANGE WHICH

4509
02:37:00,400 --> 02:37:01,800
GAVE UPS THE SUBTYPE

4510
02:37:01,800 --> 02:37:04,240
CLASSIFICATION AND ALSO HAD THE

4511
02:37:04,240 --> 02:37:06,200
PSA95 HALO TAG SHES PROTEIN

4512
02:37:06,200 --> 02:37:06,480
LIFETIME.

4513
02:37:06,480 --> 02:37:08,600
AS SHOWN IN THESE GRAPHS BELOW

4514
02:37:08,600 --> 02:37:10,880
HERE, THE GRAPH BELOW, WE'VE

4515
02:37:10,880 --> 02:37:12,640
RANKED THE SUBTYPES ACHORD TO GO

4516
02:37:12,640 --> 02:37:14,280
THEIR PROTEIN LIFETIME --

4517
02:37:14,280 --> 02:37:15,640
ACCORDING TO THEIR PROTEIN

4518
02:37:15,640 --> 02:37:16,200
LIFETIME.

4519
02:37:16,200 --> 02:37:18,120
IT'S CLEAR THERE ARE SOME

4520
02:37:18,120 --> 02:37:19,120
SUBTYPES THOSE SHOWN ON THE

4521
02:37:19,120 --> 02:37:20,880
LEFT-HAND SIDE WHICH ARE LONG

4522
02:37:20,880 --> 02:37:22,920
PROTEIN SYNAPSE SUBTYPES AND FAR

4523
02:37:22,920 --> 02:37:24,600
RIGHT THERE ARE THOSE WITH SHORT

4524
02:37:24,600 --> 02:37:26,440
PROTEIN LIFETIMES.

4525
02:37:26,440 --> 02:37:28,200
SO IN OTHER WORDS, THESE

4526
02:37:28,200 --> 02:37:29,840
SUBTYPES OF SYNAPSES WITH

4527
02:37:29,840 --> 02:37:31,560
DIFFERENT LIFETIMES ARE REALLY

4528
02:37:31,560 --> 02:37:33,080
FUNDAMENTAL BUILDING BLOCKS OF

4529
02:37:33,080 --> 02:37:34,880
THE SYNAPTOME AND THEY'RE

4530
02:37:34,880 --> 02:37:35,560
POPULATING DIFFERENT AREAS OF

4531
02:37:35,560 --> 02:37:36,280
THE BRAIN.

4532
02:37:36,280 --> 02:37:37,520
LET'S GET BACK TO THIS PICTURE

4533
02:37:37,520 --> 02:37:39,440
THAT I SHOWED YOU EARLIER ABOUT

4534
02:37:39,440 --> 02:37:41,560
THESE VERY INTERESTING DIFFERENT

4535
02:37:41,560 --> 02:37:43,600
SUBTYPES OF SYNAPSE THAT IS ARE

4536
02:37:43,600 --> 02:37:45,400
ON ONE HAND AGE SENSITIVE AND

4537
02:37:45,400 --> 02:37:46,640
AGE RESISTANT AND IT TURNS OUT

4538
02:37:46,640 --> 02:37:47,880
IT WOULD BE VERY NICE THAT THE

4539
02:37:47,880 --> 02:37:49,440
PROTEINS THAT HAVE THE SHORT

4540
02:37:49,440 --> 02:37:51,360
PROTEIN LIFETIME ARE THE AGE

4541
02:37:51,360 --> 02:37:52,520
SENSITIVE ONES AND IN OTHER

4542
02:37:52,520 --> 02:37:55,240
WORDS RAPIDLY TURN OAFERG,

4543
02:37:55,240 --> 02:37:57,280
RAPIDLY REMODELING AND THOSE ARE

4544
02:37:57,280 --> 02:37:58,920
RESISTANT TO OLD AGE HAVE THE

4545
02:37:58,920 --> 02:38:01,920
ONES WITH LONG PROTEIN LIFETIME.

4546
02:38:01,920 --> 02:38:03,320
WE THINK THERE'S SOMETHING VERY

4547
02:38:03,320 --> 02:38:05,760
SPECIAL ABOUT THAT, THAT IS TO

4548
02:38:05,760 --> 02:38:08,520
SAY APPEARS THE ANIMAL IS AGING,

4549
02:38:08,520 --> 02:38:11,320
SLOW SYNAPSE RS PREZIL YENT TO

4550
02:38:11,320 --> 02:38:12,520
WHATEVER LOSSES MIGHT OCCUR.

4551
02:38:12,520 --> 02:38:14,160
SO WE'VE ALSO DONE A STUDY

4552
02:38:14,160 --> 02:38:17,360
ACROSS THE LIFE SPAN AT THE

4553
02:38:17,360 --> 02:38:19,000
PROTEIN LIFETIME AND SEE HERE

4554
02:38:19,000 --> 02:38:21,320
THREE BRAIN MAPS AT THREE WEEKS,

4555
02:38:21,320 --> 02:38:23,040
THREE MONTHS AND 128 MONTHS.

4556
02:38:23,040 --> 02:38:25,280
THERE'S A VERY -- AND 18 MONTHS.

4557
02:38:25,280 --> 02:38:26,560
THERE'S A VERY CLEAR TREAND

4558
02:38:26,560 --> 02:38:29,600
CROSS THE LIFE SPAN WHERE THE

4559
02:38:29,600 --> 02:38:31,600
PROTEIN LIFETIME INCREASES

4560
02:38:31,600 --> 02:38:32,920
AGGRESSIVELY GENERALLY IN ALL

4561
02:38:32,920 --> 02:38:34,320
AREAS OF THE BRAIN APPEARS THE

4562
02:38:34,320 --> 02:38:35,000
ANIMAL GETS OLDER.

4563
02:38:35,000 --> 02:38:37,960
SO IN ESSENCE WHAT THIS MEANS

4564
02:38:37,960 --> 02:38:38,920
AND THIS IS CONSISTENT WITH

4565
02:38:38,920 --> 02:38:40,080
OTHER STUDIES THAT HAVE THIS

4566
02:38:40,080 --> 02:38:42,440
SEASON THAT PROTO PROTEOSTASIS

4567
02:38:42,440 --> 02:38:44,800
SLOWS DOWN AS ANIMALS AGE.

4568
02:38:44,800 --> 02:38:46,400
SO I WOULD JUST LIKE TO FINISH

4569
02:38:46,400 --> 02:38:48,200
HERE BY REALLY EMPHASIZING THE

4570
02:38:48,200 --> 02:38:50,640
IMPORTANCE OF WHAT ARE NOW THREE

4571
02:38:50,640 --> 02:38:52,440
PARAMETERS, QUANTITY OF THE

4572
02:38:52,440 --> 02:38:54,040
PROTEIN, THE MORPHOLOGY THAT IS

4573
02:38:54,040 --> 02:38:55,880
REALLY THE NANO ARCHITECTURE OF

4574
02:38:55,880 --> 02:38:57,560
THE PROTEINS AND THE PROTEIN

4575
02:38:57,560 --> 02:39:00,280
LIFETIME AND EACH OF THESE VARY

4576
02:39:00,280 --> 02:39:03,240
BETWEEN SYNAPSES AND THESE THREE

4577
02:39:03,240 --> 02:39:04,760
FUNDAMENTAL COMPONENTS REALLY

4578
02:39:04,760 --> 02:39:07,360
ARE KEY TO THE SYNAPSE DIVERSITY

4579
02:39:07,360 --> 02:39:11,040
OF THE NERVOUS SYSTEM AND THESE

4580
02:39:11,040 --> 02:39:12,800
DIFFERENT DIVERSE SYNAPSES ARE

4581
02:39:12,800 --> 02:39:14,240
THEN DISTRIBUTED AND ORGANIZED

4582
02:39:14,240 --> 02:39:16,400
IN THE BRAIN TO GIVE THIS

4583
02:39:16,400 --> 02:39:18,200
SYNAPTOME ARCHITECTURE AND

4584
02:39:18,200 --> 02:39:19,480
UNDOUBTEDLY UNDERLIE KEY

4585
02:39:19,480 --> 02:39:21,240
FUNCTIONS WHETHER THEY BE

4586
02:39:21,240 --> 02:39:24,080
SYNAPTIC TRANSFORMATION MISSION

4587
02:39:24,080 --> 02:39:26,400
AND SYNAPTIC PLASTICITY AND EVEN

4588
02:39:26,400 --> 02:39:27,080
MEMORY FUNCTIONS.

4589
02:39:27,080 --> 02:39:28,240
WITH THAT I'LL FINISH AND THANK

4590
02:39:28,240 --> 02:39:30,080
YOU FOR YOUR TIME.

4591
02:39:30,080 --> 02:39:32,080
BUT I WANT TO TELL YOU WHO HAS

4592
02:39:32,080 --> 02:39:35,240
REALLY DONE THIS MAIN WORK, I'VE

4593
02:39:35,240 --> 02:39:38,760
MENTIONED THAT ADIDA GUVALADE

4594
02:39:38,760 --> 02:39:42,720
HAS LED THIS AND -- PLAYED A KEY

4595
02:39:42,720 --> 02:39:45,560
ROLE IN THE DESIGN AND MICE AND

4596
02:39:45,560 --> 02:39:46,960
RICKY IS SPECIAL CONSIDERATION

4597
02:39:46,960 --> 02:39:49,520
GIVEN THAT GIVEN THAT HE'S

4598
02:39:49,520 --> 02:39:52,120
DEVELOPED THIS SPECIAL IMAGING

4599
02:39:52,120 --> 02:39:57,240
PIPELINE FOR THE SYNAPTOME

4600
02:39:57,240 --> 02:39:57,480
MAPPING.

4601
02:39:57,480 --> 02:39:58,000
THANK YOU VERY MUCH.

4602
02:39:58,000 --> 02:39:59,800
>> I WOULD LIKE TO THANK
ALL THE

4603
02:39:59,800 --> 02:40:01,440
SPEAKERS FOR THEIR WONDERFUL

4604
02:40:01,440 --> 02:40:01,960
TALKS.

4605
02:40:01,960 --> 02:40:05,040
AND NOW WE HAVE SOME TIME FOR

4606
02:40:05,040 --> 02:40:09,920
QUESTIONS FOR FOLKS LISTENING

4607
02:40:09,920 --> 02:40:10,080
IN.

4608
02:40:10,080 --> 02:40:13,200
PLEASE USE THE Q & A TAB ON
THE

4609
02:40:13,200 --> 02:40:17,520
RIGHT SIDE PANEL OF YOUR BROWSER

4610
02:40:17,520 --> 02:40:20,960
TO ADD QUESTIONS THAT I WILL

4611
02:40:20,960 --> 02:40:23,080
SUBSEQUENTLY FOAPS THE

4612
02:40:23,080 --> 02:40:25,360
SPEAKERS -- POSE TO THE

4613
02:40:25,360 --> 02:40:25,600
SPEAKERS.

4614
02:40:25,600 --> 02:40:26,280
LET'S SEE.

4615
02:40:26,280 --> 02:40:30,760
FIRST OF ALL, TWO QUESTIONS FOR

4616
02:40:30,760 --> 02:40:31,200
SETH.

4617
02:40:31,200 --> 02:40:32,840
FIRST, DO YOU EXPECT THESE

4618
02:40:32,840 --> 02:40:35,040
CHANGES IN SYNAPSE SUBTYPES OVER

4619
02:40:35,040 --> 02:40:37,600
AGE TO BE DRIVEN BY EPIGENETIC

4620
02:40:37,600 --> 02:40:40,280
CHANGED OR MORE LOCAL CHANGES IN

4621
02:40:40,280 --> 02:40:44,720
THE SYNAPTIC MOLECULAR NETWORK?

4622
02:40:44,720 --> 02:40:46,520
>> THAT'S A GOOD QUESTION
ABOUT

4623
02:40:46,520 --> 02:40:47,320
EPIGENETIC CHANGED.

4624
02:40:47,320 --> 02:40:49,080
WE CERTAINLY KNOW THAT THERE ARE

4625
02:40:49,080 --> 02:40:50,920
TRANSCRIPTIONAL CHANGES

4626
02:40:50,920 --> 02:40:51,200
INVOLVED.

4627
02:40:51,200 --> 02:40:52,360
UP UNTIL THE FIRST THREE MONTHS

4628
02:40:52,360 --> 02:40:53,240
OF AGE.

4629
02:40:53,240 --> 02:40:56,560
BUT THESE LIFETIME CHANGES THAT

4630
02:40:56,560 --> 02:40:58,040
OCCUR N OUR SCIENCE PAPER WE

4631
02:40:58,040 --> 02:40:59,600
SHOWED THAT FROM THREE MONTHS OF

4632
02:40:59,600 --> 02:41:02,320
AGE OUT TO ABOUT 18 MONTHS IT'S

4633
02:41:02,320 --> 02:41:04,400
A SLOW CS SET OF CHANGES

4634
02:41:04,400 --> 02:41:05,560
AFFECTING SOME OF THE SUBTYPES.

4635
02:41:05,560 --> 02:41:08,440
I THINK THERE'S GOING TO BE

4636
02:41:08,440 --> 02:41:09,040
POST-TRANSCRIPTIONAL MECHANISM

4637
02:41:09,040 --> 02:41:10,000
IN ADDITION TO TRANSCRIPTIONAL

4638
02:41:10,000 --> 02:41:11,880
REGULATION, FOR EXAMPLE, THEAZ

4639
02:41:11,880 --> 02:41:14,160
EFFECTS ON TRANSLATION PROTEIN

4640
02:41:14,160 --> 02:41:15,680
LIFETIME ARE GOING TO BE -- I

4641
02:41:15,680 --> 02:41:17,200
THINK ALL OF THESE FACTORS WILL

4642
02:41:17,200 --> 02:41:19,080
CONTRIBUTE IN SOME WAY TO THE

4643
02:41:19,080 --> 02:41:20,600
SYNAPTOME ARCHITECTURE AND AN

4644
02:41:20,600 --> 02:41:21,720
IMPORTANT POINT I WANT TO

4645
02:41:21,720 --> 02:41:23,680
EMPHASIZE HERE IS THAT WHEN ONE

4646
02:41:23,680 --> 02:41:25,200
UNDERSTANDS THESE VERY

4647
02:41:25,200 --> 02:41:26,200
ELEMENTARY MOLECULAR PRINCIPLES

4648
02:41:26,200 --> 02:41:31,760
SUCH AS REGULATION OF PROMOTOME

4649
02:41:31,760 --> 02:41:34,880
FOR EXAMPLE IT CAN EXPLAIN WHY

4650
02:41:34,880 --> 02:41:37,160
MUTATIONS LEAD TO CHANGES IN THE

4651
02:41:37,160 --> 02:41:39,120
SYNAPTIC ARCHITECTURE WHICH IN

4652
02:41:39,120 --> 02:41:40,080
TURN PRODUCE BEHAVIORAL

4653
02:41:40,080 --> 02:41:42,240
DISPLAING WO CAN I QUICKLY

4654
02:41:42,240 --> 02:41:42,520
FOLLOW UP.

4655
02:41:42,520 --> 02:41:44,280
>> CAN I QUICKLY FOLLOW UP
WITH

4656
02:41:44,280 --> 02:41:45,480
A SLIGHTLY DIFFERENT QUESTION,

4657
02:41:45,480 --> 02:41:47,040
WHICH IS DO YOU SEE MORE

4658
02:41:47,040 --> 02:41:49,520
DIVERSITY IN KIND OF THE

4659
02:41:49,520 --> 02:41:52,320
PRESYNAPTIC OR POSTSYNAPTIC KIND

4660
02:41:52,320 --> 02:41:54,040
OF COMPARTMENTS IN TRMS OF BOTH

4661
02:41:54,040 --> 02:41:55,400
DIVERSITY AND LIFETIME?

4662
02:41:55,400 --> 02:41:58,680
>> NO, WE FOCUSED MOST OF
OUR

4663
02:41:58,680 --> 02:41:59,640
ATTENTION ON THE POSTSYNAPTIC

4664
02:41:59,640 --> 02:41:59,960
SIDE.

4665
02:41:59,960 --> 02:42:01,520
WE CERTAINLY HAVE DONE SOME

4666
02:42:01,520 --> 02:42:04,440
LIMITED STUDIES ON PRESYNAPTIC

4667
02:42:04,440 --> 02:42:05,440
TERMINALS AND THERE'S CERTAINLY

4668
02:42:05,440 --> 02:42:06,960
A LOT OF DIVERSITY THERE TOO.

4669
02:42:06,960 --> 02:42:08,320
I THINK THESE ARE GENERAL

4670
02:42:08,320 --> 02:42:10,040
PRINCIPLES THAT APPLY BOTH TO

4671
02:42:10,040 --> 02:42:11,240
PRE AND TO POST, BUT THERE'S

4672
02:42:11,240 --> 02:42:13,000
OBVIOUSLY A LOT OF VERY KEY

4673
02:42:13,000 --> 02:42:14,760
SPECIFIC QUESTIONS TO LOOK AT IN

4674
02:42:14,760 --> 02:42:15,200
BOTH CIRCUMSTANCES.

4675
02:42:15,200 --> 02:42:18,800
>> EXCELLENT.

4676
02:42:18,800 --> 02:42:21,240
IS THERE A PLAN TO COMBINE ALL

4677
02:42:21,240 --> 02:42:22,280
CONNECT TOMORROW SYNAPTOME

4678
02:42:22,280 --> 02:42:28,040
EFFORTS IN THE END OR WILL

4679
02:42:28,040 --> 02:42:30,000
GENALIA STAY SEPARATE SOME

4680
02:42:30,000 --> 02:42:31,760
PLATFORMS LIKE FLY WIRE?

4681
02:42:31,760 --> 02:42:36,120
PERHAPS CLAIRE CAN START WITH

4682
02:42:36,120 --> 02:42:37,120
THAT, ALTHOUGH UNFORTUNATELY

4683
02:42:37,120 --> 02:42:39,840
MICHAEL IS NOT WITH US FOR THE Q

4684
02:42:39,840 --> 02:42:40,200
& A PORTION.

4685
02:42:40,200 --> 02:42:41,680
>> IT'S MY DREAM THAT
SCIENCE

4686
02:42:41,680 --> 02:42:43,120
WILL BECOME MORE AND MORE OPEN

4687
02:42:43,120 --> 02:42:44,760
SO WE'VE TRIED TO SET AN EXAMPLE

4688
02:42:44,760 --> 02:42:49,040
THERE, AND WE HOPE THAT OTHER

4689
02:42:49,040 --> 02:42:50,840
PEOPLE WILL BE INTERESTED IN

4690
02:42:50,840 --> 02:42:52,960
COLLABORATING AS MUCH AS

4691
02:42:52,960 --> 02:42:53,280
POSSIBLE.

4692
02:42:53,280 --> 02:42:57,400
SO I'VE REALLY ENJOYED HOW MUCH

4693
02:42:57,400 --> 02:43:02,680
THE PROJECT BETWEEN GENELIA AND

4694
02:43:02,680 --> 02:43:04,520
FLY WIRE HAS BEEN TRACKED AND I

4695
02:43:04,520 --> 02:43:05,760
HOPE TM CONTINUE TO GROAVMENT

4696
02:43:05,760 --> 02:43:07,520
ADDING IN SYNAPTOME I'LL LET

4697
02:43:07,520 --> 02:43:09,800
SETH SPEAK TO THAT MAYBE.

4698
02:43:09,800 --> 02:43:11,640
>> I WOULD JUST LIKE TO
SAY ONE

4699
02:43:11,640 --> 02:43:12,960
THING ABOUT IT, AND I THINK IT'S

4700
02:43:12,960 --> 02:43:15,240
VERY OBVIOUS TO EVERYBODY, WHEN

4701
02:43:15,240 --> 02:43:17,320
ONE DESCRIBES THE CONNECT OHM

4702
02:43:17,320 --> 02:43:18,840
AND SOME WHO HAVE DONE ALREADY

4703
02:43:18,840 --> 02:43:20,400
HERE TODAY AND MANY OTHERS HAVE

4704
02:43:20,400 --> 02:43:21,800
DONE TOO, IT'S USUALLY IN TERMS

4705
02:43:21,800 --> 02:43:24,040
OF THE PHYSICAL LOCATION OF THE

4706
02:43:24,040 --> 02:43:26,440
SYNAPSES WITH RESPECT TO THE

4707
02:43:26,440 --> 02:43:29,360
DENDRITES AND AXONAL PROJECTIONS

4708
02:43:29,360 --> 02:43:33,040
AND OBVIOUSLY THE MOLECULAR

4709
02:43:33,040 --> 02:43:34,640
COMPOSITION MAP OF ALL OF THOSE

4710
02:43:34,640 --> 02:43:36,080
SYNAPSE AND IS CLEARLY THESE TWO

4711
02:43:36,080 --> 02:43:37,560
THINGS NEED TO BE INTEGRATED AND

4712
02:43:37,560 --> 02:43:39,360
THERE'S A WHOLE LOT OF TECHNICAL

4713
02:43:39,360 --> 02:43:40,120
CHALLENGES ASSOCIATED WITH THAT

4714
02:43:40,120 --> 02:43:41,400
AND SOME OF WHICH WE'RE WORKING

4715
02:43:41,400 --> 02:43:42,720
ON BUT OBVIOUSLY THESE ALL HAVE

4716
02:43:42,720 --> 02:43:44,280
TO BE PUT TOGETHER AT SOME POINT

4717
02:43:44,280 --> 02:43:45,240
BECAUSE IF YOU DON'T HAVE THE

4718
02:43:45,240 --> 02:43:49,960
MOLECULES IN YOUR CONNECT OHM --

4719
02:43:49,960 --> 02:43:52,160
IN YOUR CONNECTOME, YOU DON'T

4720
02:43:52,160 --> 02:43:54,760
HAVE THE FUNCTION.

4721
02:43:54,760 --> 02:43:58,200
>> I GUESS I WOULD ADD, I
WOULD

4722
02:43:58,200 --> 02:44:00,800
ECHO CLAIRE AND KIND OF ADD THAT

4723
02:44:00,800 --> 02:44:05,160
IN GENERAL, THESE CONNECTOMICS

4724
02:44:05,160 --> 02:44:08,920
DATA SETS ARE BEING PUT OUT TO

4725
02:44:08,920 --> 02:44:11,760
THE PUBLIC AT SOME POINT SUCH

4726
02:44:11,760 --> 02:44:13,760
THAT PEOPLE CAN, YOU KNOW, THAT

4727
02:44:13,760 --> 02:44:15,840
THE DATASETS THEMSELVES PROVIDE

4728
02:44:15,840 --> 02:44:17,920
AN OPPORTUNITY TO FUEL FURTHER

4729
02:44:17,920 --> 02:44:21,240
KIND OF SCIENCE AND DISCOVERY,

4730
02:44:21,240 --> 02:44:23,240
BUT THERE IS A CHALLENGE OF KIND

4731
02:44:23,240 --> 02:44:25,040
OF INTEGRATING DIFFERENT

4732
02:44:25,040 --> 02:44:26,440
MODALITIES, FOR EXAMPLE, IN

4733
02:44:26,440 --> 02:44:27,320
DIFFERENT SAMPLES.

4734
02:44:27,320 --> 02:44:30,120
BUT I THINK THIS IS HOPEFULLY

4735
02:44:30,120 --> 02:44:32,800
FOOD FOR THE FUTURE.

4736
02:44:32,800 --> 02:44:34,680
HI, CLAIRE, IS THERE ANY PLAN TO

4737
02:44:34,680 --> 02:44:37,280
PROOFREAD THE AUTO-DETECTED

4738
02:44:37,280 --> 02:44:39,600
SYNAPSE INSIDE FLY WIRE?

4739
02:44:39,600 --> 02:44:43,400
>> THAT WOULD BE GREAT.

4740
02:44:43,400 --> 02:44:45,280
RIGHT NOW, NOT IMMEDIATELY.

4741
02:44:45,280 --> 02:44:47,560
BUT WE ARE GOING TO HAVE SUCH A

4742
02:44:47,560 --> 02:44:49,880
NUMBER OF HUMAN RESOURCES THAT

4743
02:44:49,880 --> 02:44:51,640
AFTER THE NEURONS HAVE BEEN

4744
02:44:51,640 --> 02:44:52,840
PROOFREAD, IT MIGHT MAKE SENSE

4745
02:44:52,840 --> 02:44:55,000
TO TURN THE WORLD'S ATTENTION TO

4746
02:44:55,000 --> 02:44:58,640
THE SYNAPSES.

4747
02:44:58,640 --> 02:45:00,680
ZOOG OBJECTIVE.

4748
02:45:00,680 --> 02:45:01,440
>> OKAY.

4749
02:45:01,440 --> 02:45:03,240
THE SYNAPSE PREDICTION, THE KIND

4750
02:45:03,240 --> 02:45:05,520
OF PRECISION RECALL OF THE

4751
02:45:05,520 --> 02:45:07,080
AUTO-DETECTED SYNAPSES IS FAIRLY

4752
02:45:07,080 --> 02:45:09,040
GOOD, NOT PERFECT, OBVIOUSLY,

4753
02:45:09,040 --> 02:45:09,240
BUT --

4754
02:45:09,240 --> 02:45:13,320
>> IT IS, BUT THE SHEER
NUMBERS

4755
02:45:13,320 --> 02:45:15,360
MAKE IT ALMOST IMPOSSIBLE FOR

4756
02:45:15,360 --> 02:45:16,720
HUMAN INTERVENTION, BUT THERE

4757
02:45:16,720 --> 02:45:18,120
COULD BE HUMAN INTERVENTION AT

4758
02:45:18,120 --> 02:45:22,320
SOME KIND OF SCALE.

4759
02:45:22,320 --> 02:45:24,720
>> SO A QUESTION FOR BEN.

4760
02:45:24,720 --> 02:45:26,240
IT'S FASCINATING THAT THE MOTOR

4761
02:45:26,240 --> 02:45:28,760
BEHAVIOR STAYS THE SAME DURING

4762
02:45:28,760 --> 02:45:30,000
C. ELEGANS MATURATION WHILE

4763
02:45:30,000 --> 02:45:31,680
MOTOR NEURONS ARE REMODELED.

4764
02:45:31,680 --> 02:45:33,040
COULD YOU MAKE ANY PREDICTIONS

4765
02:45:33,040 --> 02:45:35,200
ABOUT SYSTEM WHERE THE BEHAVIOR

4766
02:45:35,200 --> 02:45:36,360
ACTUALLY CHANGES BUT STILL USES

4767
02:45:36,360 --> 02:45:37,840
THE SAME MOTOR NEURONS?

4768
02:45:37,840 --> 02:45:40,640
FOR EXAMPLE, FLY LARVA AND

4769
02:45:40,640 --> 02:45:41,840
ADULTS SHARE MANY OF THE SAME

4770
02:45:41,840 --> 02:45:44,480
MOTOR NEURONS FOR FEEDING BUT

4771
02:45:44,480 --> 02:45:46,200
COMPLETELY DIFFERENT MOTOR

4772
02:45:46,200 --> 02:45:46,440
NEURONS.

4773
02:45:46,440 --> 02:45:48,000
DO YOU EXPECT MODELING

4774
02:45:48,000 --> 02:45:49,520
MECHANISMS YOU FOUND COULD APPLY

4775
02:45:49,520 --> 02:45:53,120
IN SYSTEMS LIKE THAT?

4776
02:45:53,120 --> 02:45:54,680
>> YEAH.

4777
02:45:54,680 --> 02:45:57,760
SO I DON'T KNOW MUCH ABOUT THE

4778
02:45:57,760 --> 02:46:02,440
TIMING OF DROSOPHILA, BUT

4779
02:46:02,440 --> 02:46:04,200
DROSOPHILA CHEATS AND THEY GO

4780
02:46:04,200 --> 02:46:06,280
INTO THE PEOPLE STAGE.

4781
02:46:06,280 --> 02:46:07,480
COINCIDE WITH THAT.

4782
02:46:07,480 --> 02:46:08,720
IN WHICH CASE IT MIGHT BE KIND

4783
02:46:08,720 --> 02:46:10,640
OF LESS CONSTRAINED IN

4784
02:46:10,640 --> 02:46:17,560
MAINTAINING FUNCTION.

4785
02:46:17,560 --> 02:46:23,120
>> OKAY.

4786
02:46:23,120 --> 02:46:24,440
FOR STEPHANIE.

4787
02:46:24,440 --> 02:46:26,840
BEYOND THE MECHANOSENSORY

4788
02:46:26,840 --> 02:46:28,720
NEURONS YOU FOUND, HOW

4789
02:46:28,720 --> 02:46:29,560
SEGREGATED DO YOU THINK THE

4790
02:46:29,560 --> 02:46:31,120
INFORMATION WILL REMAIN OR LIKE

4791
02:46:31,120 --> 02:46:33,720
WHEN DOES IT GET INTEGRATED TO

4792
02:46:33,720 --> 02:46:35,480
PROPAGATE DOWN TO KIND OF

4793
02:46:35,480 --> 02:46:36,680
DOWNSTREAM CIRCUITS, GROOMING

4794
02:46:36,680 --> 02:46:38,440
CIRCUITS AND KIND OF ULTIMATELY

4795
02:46:38,440 --> 02:46:40,520
MOTOR NEURONS THAT ARE EXECUTING

4796
02:46:40,520 --> 02:46:44,200
THESE GROOMING BEHAVIORS?

4797
02:46:44,200 --> 02:46:46,520
>> YEAH, WE HAVE ACTUALLY

4798
02:46:46,520 --> 02:46:48,840
RECONSTRUCTED THE ENTIRE NETWORK

4799
02:46:48,840 --> 02:46:53,240
IN THE BRAIN SO IT BASICALLY

4800
02:46:53,240 --> 02:46:56,520
GOES THROUGH ABOUT TWO LAYERS OF

4801
02:46:56,520 --> 02:46:57,920
NEURONS IN THE BRAIN AND THEN ON

4802
02:46:57,920 --> 02:46:59,760
THE VENTRAL NERVOUS SYSTEM,

4803
02:46:59,760 --> 02:47:05,240
WHICH WE ALSO HAVE STARTED IN

4804
02:47:05,240 --> 02:47:07,000
WAYS WHICH I HAVEN'T TALKED

4805
02:47:07,000 --> 02:47:09,080
ABOUT TODAY, AND A LOT OF THE

4806
02:47:09,080 --> 02:47:11,040
DESCENDING NEURONS ARE DIRECTLY

4807
02:47:11,040 --> 02:47:15,440
CONNECTED TO MOTOR OUTPUTS.

4808
02:47:15,440 --> 02:47:20,040
SO YEAH.

4809
02:47:20,040 --> 02:47:22,560
>> EXCELLENT.

4810
02:47:22,560 --> 02:47:24,280
WELL, I THINK I HAVEN'T ASKED

4811
02:47:24,280 --> 02:47:24,880
THIS QUESTION.

4812
02:47:24,880 --> 02:47:26,080
THIS IS FOR SETH.

4813
02:47:26,080 --> 02:47:27,720
WHAT ARE SOME OF THE MAJOR

4814
02:47:27,720 --> 02:47:30,320
BARRIERS RELATING SYNAPTOME

4815
02:47:30,320 --> 02:47:31,960
TOAMS AS DESCRIBED TO YOU TO

4816
02:47:31,960 --> 02:47:33,760
MOLECULARLY AND ANATOMICALLY

4817
02:47:33,760 --> 02:47:35,560
DESCRIBED CIRCUITS AT SOME

4818
02:47:35,560 --> 02:47:37,320
CELLULAR SCALE IN SOME OTHER

4819
02:47:37,320 --> 02:47:37,840
TALKS?

4820
02:47:37,840 --> 02:47:39,200
>> THE QUESTION THAT WE
ARE

4821
02:47:39,200 --> 02:47:40,560
WORKING ON AT THE MOMENT WHICH

4822
02:47:40,560 --> 02:47:42,480
MAY ADDRESS THAT IS TO DEVELOP

4823
02:47:42,480 --> 02:47:45,080
CELL TYPE SPECIFIC WAYS OF DOING

4824
02:47:45,080 --> 02:47:47,440
SYNAPTOME LABELING AND FOR

4825
02:47:47,440 --> 02:47:52,080
EXAMPLE USING PRELOX P METHODS

4826
02:47:52,080 --> 02:47:52,960
WHERE YOU CAN CONDITIONALLY

4827
02:47:52,960 --> 02:47:54,080
TAPPING THE MOLECULES.

4828
02:47:54,080 --> 02:47:56,280
THAT WORKS QUITE NICELY.

4829
02:47:56,280 --> 02:47:58,080
WHAT WE NEED TO DO AND AGAIN I

4830
02:47:58,080 --> 02:48:00,520
THINK THERE'S A LOT OF

4831
02:48:00,520 --> 02:48:02,520
TECHNOLOGY IN THE CONNECTOMICS

4832
02:48:02,520 --> 02:48:05,360
WORLD THAT -- IN THE

4833
02:48:05,360 --> 02:48:06,640
CONNECTOMICS WORLD THAT HASN'T

4834
02:48:06,640 --> 02:48:11,680
BEEN EXPLORED, RS THE LONG

4835
02:48:11,680 --> 02:48:13,320
RANGE, I WOULD BE INTERESTED TO

4836
02:48:13,320 --> 02:48:14,560
TALK WITH PEOPLE ABOUT THAT

4837
02:48:14,560 --> 02:48:16,000
SHOULD THEY HAVE AN INTEREST IN

4838
02:48:16,000 --> 02:48:17,040
DOING THAT.

4839
02:48:17,040 --> 02:48:19,680
>> AND THANKS FOR THE
GREAT

4840
02:48:19,680 --> 02:48:19,880
TALKS.

4841
02:48:19,880 --> 02:48:21,120
I HAVE A QUESTION FOR THE GROUP.

4842
02:48:21,120 --> 02:48:23,760
WHAT DO YOU SEE AS A

4843
02:48:23,760 --> 02:48:25,280
RATE-LIMITING STEPS IN TERMS OF

4844
02:48:25,280 --> 02:48:27,240
SCALING PROOFREAD TO GO LARGER

4845
02:48:27,240 --> 02:48:28,680
VOLUMES, FOR EXAMPLE, MAMMALIAN

4846
02:48:28,680 --> 02:48:30,880
BRAINS OR MULTIPLE SMALL BRAINS

4847
02:48:30,880 --> 02:48:32,680
OF THE SAME SPECIES SAMPLED

4848
02:48:32,680 --> 02:48:33,720
UNDER DIFFERENT CONDITIONS OR

4849
02:48:33,720 --> 02:48:36,480
GENETIC BACKGROUNDS?

4850
02:48:36,480 --> 02:48:37,320
MAYBE CLAIRE CAN START.

4851
02:48:37,320 --> 02:48:38,680
>> CAN I TAKE THAT ONE?

4852
02:48:38,680 --> 02:48:39,840
>> SURE, YES.

4853
02:48:39,840 --> 02:48:41,840
>> I THINK THAT IT WOULD
BE

4854
02:48:41,840 --> 02:48:44,560
GREAT TO HAVE MORE AUTOMATED

4855
02:48:44,560 --> 02:48:49,320
ERROR DETECTION USING HEURISTICS

4856
02:48:49,320 --> 02:48:52,600
LIKE BEING ABLE TO MAKE

4857
02:48:52,600 --> 02:48:54,120
PREDICTIONS ABOUT AXONS VERSUS

4858
02:48:54,120 --> 02:48:55,640
DEN DRIETD AND SAY, WELL, THIS

4859
02:48:55,640 --> 02:48:57,840
IS A PIECE OF AXON STUCK TO A

4860
02:48:57,840 --> 02:48:59,600
DEN TRANSMIT I CAN TREE SO HUMAN

4861
02:48:59,600 --> 02:49:03,000
PLEASE GO LOOK THERE, OR, YOU

4862
02:49:03,000 --> 02:49:05,400
KNOW, RS -- SUPPOSED TO BE FROM

4863
02:49:05,400 --> 02:49:08,320
THICK TO THIN, SO WHY IS THIS

4864
02:49:08,320 --> 02:49:08,680
BRANCH THICK?

4865
02:49:08,680 --> 02:49:11,200
SO OBVIOUSLY THE BETTER THE

4866
02:49:11,200 --> 02:49:13,400
ALGORITHMS BECOME, THEN THE LESS

4867
02:49:13,400 --> 02:49:14,800
HUMAN INVOLVEMENT IS NEEDED BUT

4868
02:49:14,800 --> 02:49:16,920
AS YOU SCALE UP, ACTUAL ACTUALLY

4869
02:49:16,920 --> 02:49:18,320
THE MORE HUMAN INVOLVEMENT IS

4870
02:49:18,320 --> 02:49:20,520
NEEDED BUT WE NEED MORE TOOLS TO

4871
02:49:20,520 --> 02:49:25,600
MAKE HUMANS' JOBS EASIER.

4872
02:49:25,600 --> 02:49:28,640
>> YEAH, I WOULD ECHO
THAT.

4873
02:49:28,640 --> 02:49:29,760
THERE'S BEEN SUBSTANTIAL

4874
02:49:29,760 --> 02:49:31,720
PROGRESS IN TERMS OF LIKE

4875
02:49:31,720 --> 02:49:33,920
JAINTING THESE TYPES OF DATA --

4876
02:49:33,920 --> 02:49:35,240
GENERATING THESE TYPES OF DATA

4877
02:49:35,240 --> 02:49:36,520
AND THEN SUBSEQUENTLY KIND OF

4878
02:49:36,520 --> 02:49:38,280
DOING THE INITIAL KIND OF

4879
02:49:38,280 --> 02:49:41,480
SEGMENTATION AND THINGS LIKE

4880
02:49:41,480 --> 02:49:43,440
SYNAPSE PREDICTION BUT KIND OF

4881
02:49:43,440 --> 02:49:46,520
THE BOTTLENECK AT THIS POINT AND

4882
02:49:46,520 --> 02:49:48,360
CONTINUES TO BE KIND OF THE

4883
02:49:48,360 --> 02:49:52,000
PROOFREADING AND KIND OF THE

4884
02:49:52,000 --> 02:49:54,640
DETEKS OF THOSE ERRORS AND AS

4885
02:49:54,640 --> 02:49:57,000
THE AUTOMATIC ALTHOUGH GOA

4886
02:49:57,000 --> 02:49:58,240
RHYTHMS GET BETTER AND BETTER

4887
02:49:58,240 --> 02:50:00,320
FINDING THOSE ALGORITHMS GETS

4888
02:50:00,320 --> 02:50:01,520
HARDER AND HARD AND HER THAT'S

4889
02:50:01,520 --> 02:50:02,760
WHERE THE TIME IS GOING TO BE

4890
02:50:02,760 --> 02:50:04,040
SPENT BY HUMAN EXPERTS ALTHOUGH

4891
02:50:04,040 --> 02:50:05,600
THIS ALSO DEPENDS THE QUESTIONS

4892
02:50:05,600 --> 02:50:07,200
THAT PEOPLE ARE TRYING TO

4893
02:50:07,200 --> 02:50:09,640
ADDRESS USING THESE CONNECT

4894
02:50:09,640 --> 02:50:11,480
OHMS, LIKE HOW TOLERANT THEY TO

4895
02:50:11,480 --> 02:50:14,920
KIND OF ERRORS AND THINGS LIKE

4896
02:50:14,920 --> 02:50:19,640
SEGMENTATION OR SYNAPSE

4897
02:50:19,640 --> 02:50:23,280
PREDICTION.

4898
02:50:23,280 --> 02:50:23,720
OKAY.

4899
02:50:23,720 --> 02:50:25,440
MAYBE ONE FINAL -- OH, MAYBE TWO

4900
02:50:25,440 --> 02:50:27,720
FINAL QUESTIONS.

4901
02:50:27,720 --> 02:50:30,760
THIS IS TO DR. GRANT.

4902
02:50:30,760 --> 02:50:32,920
WHAT DO YOU THINK, OR DO YOU

4903
02:50:32,920 --> 02:50:34,800
THINK LOCATION INSTRUCTS

4904
02:50:34,800 --> 02:50:36,920
DIFFERENT SYNAPSE SUBTYPES?

4905
02:50:36,920 --> 02:50:39,160
HOW DO A NEURON -- HOW DOES A

4906
02:50:39,160 --> 02:50:40,600
NEURON KNOW, FOR EXAMPLE, THAT

4907
02:50:40,600 --> 02:50:43,240
IT WANTS SYNAPSE TYPE A ON FOR

4908
02:50:43,240 --> 02:50:44,760
EXAMPLE A DISTAL DENDRITE OR

4909
02:50:44,760 --> 02:50:47,240
TYPE B ON A PROXIMAL DENDRITE,

4910
02:50:47,240 --> 02:50:49,040
FOR EXAMPLE?

4911
02:50:49,040 --> 02:50:51,760
>> WELL, I DON'T WISH TO
BE

4912
02:50:51,760 --> 02:50:53,960
FUSSY ABOUT THIS, BUT NEURONS

4913
02:50:53,960 --> 02:50:54,640
DON'T WANT ANYTHING.

4914
02:50:54,640 --> 02:50:55,360
>> SURE.

4915
02:50:55,360 --> 02:50:56,160
>>

4916
02:50:56,160 --> 02:50:57,880
>> BUT IF YOU WERE TO ASK
THE

4917
02:50:57,880 --> 02:50:59,000
QUESTION HOW DO THE MOLECULES

4918
02:50:59,000 --> 02:51:00,440
GET THERE AND HOW THEY POPULATE

4919
02:51:00,440 --> 02:51:01,520
THOSE AND MAKE DIFFERENT TYPES

4920
02:51:01,520 --> 02:51:04,960
OF SYNAPSES, FOR EXAMPLE, WE SEE

4921
02:51:04,960 --> 02:51:07,120
THERE ARE CLEAR GRADIENTS ALONG

4922
02:51:07,120 --> 02:51:09,280
THE LECT OF THE DENDRITE --

4923
02:51:09,280 --> 02:51:11,040
LENGTH OF THE DENDRITE, PROTEIN

4924
02:51:11,040 --> 02:51:12,240
PROTEIN LIFETIME AND PROTEIN

4925
02:51:12,240 --> 02:51:13,120
PROTEIN COMPOSITION AND I EXPECT

4926
02:51:13,120 --> 02:51:15,520
THAT WOULD BE DID NAITD BY VERY

4927
02:51:15,520 --> 02:51:17,440
NINTD AL CELL BIOLOGICAL

4928
02:51:17,440 --> 02:51:18,600
PRINCIPAL PRINCIPLES OF TRACK

4929
02:51:18,600 --> 02:51:22,520
AND GO SO ON AND BY DEFAULT

4930
02:51:22,520 --> 02:51:24,120
GENERATE DEN CITE DIVERSITY.

4931
02:51:24,120 --> 02:51:26,360
ALSO WE SEE PROGRAM TELL CELL

4932
02:51:26,360 --> 02:51:30,120
THAT DIFFERENT INPUTS ALONG THAT

4933
02:51:30,120 --> 02:51:31,520
DIFFERENT, YOU CAN SEE THERE ARE

4934
02:51:31,520 --> 02:51:32,960
QUITE DIFFERENT TYPES OF

4935
02:51:32,960 --> 02:51:34,800
SYNAPSES THERE AND WITHIN THE

4936
02:51:34,800 --> 02:51:36,240
THALAMUS ON AN INDIVIDUAL

4937
02:51:36,240 --> 02:51:38,520
DENDRITE YOU CAN SHOW THAT THERE

4938
02:51:38,520 --> 02:51:40,280
ARE ADJACENT SYNAPSES WHICH HAVE

4939
02:51:40,280 --> 02:51:42,480
DIFFERENT INPUTS ONE FROM THE

4940
02:51:42,480 --> 02:51:44,440
CORTEX AND ANOTHER FROM THE

4941
02:51:44,440 --> 02:51:45,240
BRAINSTEM, FOR EXAMPLE, AND THEY

4942
02:51:45,240 --> 02:51:46,880
HAVE REALLY QUITE DIFFERENT

4943
02:51:46,880 --> 02:51:51,720
SYNAPSE PROTEIN COMPOSITIONS AT

4944
02:51:51,720 --> 02:51:53,440
THE POSTSYNAPTIC SIDE.

4945
02:51:53,440 --> 02:51:56,640
RSZ CONSTRUCTIVE EFFECTS IN

4946
02:51:56,640 --> 02:51:57,800
PRESYNAPTIC PROTEINS HAVE BEEN

4947
02:51:57,800 --> 02:51:58,120
DEMONSTRATED.

4948
02:51:58,120 --> 02:52:00,200
IT WILL BE THESE SORTS OF

4949
02:52:00,200 --> 02:52:02,080
MECHANISMS THAT WILL GIVE YOU

4950
02:52:02,080 --> 02:52:05,040
THE ULTIMATE SYNAPTOME

4951
02:52:05,040 --> 02:52:05,400
ARCHITECTURE.

4952
02:52:05,400 --> 02:52:07,560
>> AND ONE FINAL QUESTION,
IT

4953
02:52:07,560 --> 02:52:10,080
LOOKS LIKE IN THE Q & A, MAY
I

4954
02:52:10,080 --> 02:52:13,080
ASK IF THERE ARE PLANS TO

4955
02:52:13,080 --> 02:52:15,880
IMPROVE SEGMENTATION/SYNAPSE

4956
02:52:15,880 --> 02:52:19,080
PREDICTION OF CELLS FOR EXAMPLE

4957
02:52:19,080 --> 02:52:22,760
WITH DARK CYTOSOL POSSIBLE

4958
02:52:22,760 --> 02:52:26,600
EXAMPLES INCLUDE GLIA IN THE EM

4959
02:52:26,600 --> 02:52:28,520
DATA?

4960
02:52:28,520 --> 02:52:28,960
CLAIRE, ARE YOU --

4961
02:52:28,960 --> 02:52:32,400
>> YES, WE ARE DOING THAT,

4962
02:52:32,400 --> 02:52:32,680
ACTUALLY.

4963
02:52:32,680 --> 02:52:35,560
SO WE'VE GENERATED NEW GROUND

4964
02:52:35,560 --> 02:52:37,880
TRUTH THAT INCLUDES CELLS WITH

4965
02:52:37,880 --> 02:52:39,600
DARKER CYTOSOL AND WE HAVE

4966
02:52:39,600 --> 02:52:41,800
RESEGMENTED AND REALIGNED THE

4967
02:52:41,800 --> 02:52:44,560
SAME FLY BRAIN DATASET THAT FLY

4968
02:52:44,560 --> 02:52:47,840
WIRE ALREADY USES, AND THERE

4969
02:52:47,840 --> 02:52:49,280
WILL BE A BIG EFFORT TO FIGURE

4970
02:52:49,280 --> 02:52:50,880
OUT HOW TO INTEGRATE THAT WITH

4971
02:52:50,880 --> 02:52:52,240
ALL OF THE HUMAN EFFORT THAT HAS

4972
02:52:52,240 --> 02:52:54,640
GONE INTO THE CURRENT DATA SET. 

4973
02:52:54,640 --> 02:52:57,040
SO WE'LL HAVE TO TALK ABOUT HOW

4974
02:52:57,040 --> 02:52:59,680
TO PHASE IN THE NEXT

4975
02:52:59,680 --> 02:53:01,200
SEGMENTATION, BUT WE HOPE THAT'S

4976
02:53:01,200 --> 02:53:03,080
COMING, AND I DO NOT YET HAVE AN

4977
02:53:03,080 --> 02:53:05,080
ANSWER FOR YOU ABOUT HOW MUCH

4978
02:53:05,080 --> 02:53:07,160
BETTER OR DARK CELLS MIGHT BE

4979
02:53:07,160 --> 02:53:08,560
SEGMENTED, BUT WE HOPE THAT THEY

4980
02:53:08,560 --> 02:53:10,120
WILL BE.

4981
02:53:10,120 --> 02:53:11,760
BUT WE OURSELVES ARE NOT

4982
02:53:11,760 --> 02:53:15,120
DIRECTLY INVOLVED IN ANY SYNAPSE

4983
02:53:15,120 --> 02:53:17,080
PREDICTION EFFORT AT THE MOMENT

4984
02:53:17,080 --> 02:53:23,160
FOR FLY WIRE.

4985
02:53:23,160 --> 02:53:24,920
>> WELL, I THINK THAT
BRINGS US

4986
02:53:24,920 --> 02:53:26,960
TO THE END OF THE Q & A
SESSION

4987
02:53:26,960 --> 02:53:29,040
AND THE SYMPOSIUM SESSION MORE

4988
02:53:29,040 --> 02:53:30,200
BROADLY SPEAKING.

4989
02:53:30,200 --> 02:53:32,400
THANK YOU AGAIN FOR EVERYONE

4990
02:53:32,400 --> 02:53:34,520
THAT HAS ATTENDED, AND THANKS

4991
02:53:34,520 --> 02:53:36,280
EVERYONE FOR THEIR QUESTIONS AND

4992
02:53:36,280 --> 00:00:00,000
THE WONDERFUL SERIES OF TALKS.