>> WELCOME, EVERYBODY.
IT'S VERY GOOD TO HAVE YOU HERE.
THIS IS THE 30th MEETING OF
THE BRAIN MULTICOUNCIL WORKING
GROUP.
I AM SUSAN WEISS, I'M THE
DIRECTOR OF THE DIVISION OF
EXTRAMURAL RESEARCH AT THE
NATIONAL INNSITUTE ON DRUG
ABUSE.
AND I AM HERE TODAY SERVING AS
THE DESIGNATED FEDERAL OFFICIAL
-- NOT FOREIGN -- FEDERAL
OFFICIAL FOR THE BRAIN
MULTICOUNCIL WORKING GROUP.
AS MANY OF YOU ALREADY KNOW THE
MCWG IS NOT A NORMAL ADVISORY
COMMITTEE UNDER THE FEDERAL
ADVISORY COMMITTEE ACT OR FACA,
IT SERVES IN AN ADVISORY ROLE TO
THE 10 ADVISORY COUNCILS THAT
ARE PART OF THE BRAIN INITIATIVE
INSTITUTES AND CENTERS EMPLOY T
WAS ESTABLISHED BECAUSE OF THE
RECOGNIZED NEEDS OF VARIOUS
EXPERT EEDZ IN VARIOUS
DISPOLICEINS IN ORDER TO
PROPERLY OVERSEE RESEARCH
SUPPORTED THROUGH BRAIN.
SOME OF THE MEMBERS ARE FROM THE
IC ADVISORY COUNCILS AND HAVE
ALSO ADDED LARGE MEMBERS TO
SUPPLEMENT THE GROUP'S WORKING
EXPERTISE, WE ALSO HAVE SEVERAL
EXOFICI IO PARTNERS, INVOLVED.
WE DEPEND UPON THE MCWG FOR
ONGOING OVERSIGHT OF THE
SCIENTIFIC VISION AND PROGRESS
OF THE BRAIN INITIATIVE FOR
FEEDBACK ON CONCEPT CLEARANCES
FOR NEW RFAs, AND FOR INPUT ON
OUR FUNDING PLANS DURING THE
CLOSED SESSION.
THE OPEN SESSION WHICH WE ARE IN
NOW, IS BEING VIDEOCAST AND
RECORDED AND WILL BE ARCHIVED
AND POSTED ON THE NIH AND BRAIN
WEBSITES.
TODAY, WE ARE PLEASED TO WELCOME
SEVERAL NEW MEMBERS TO THE MCWG
-- MCWG, DRS. EDWARD CHANG HAD
WHO IS AN AT LARGE MEMBER,
LESHON LO, AND TODD CONSTABLE
FROM NIBIB.
AND WE ARE BIDDING FAREWELL TO 3
OTHER MEMBERS, DRS. TED ABLE
FROM NIMH, TARYN MOORE FROM NEI
AND BRIAN ROTH FROM THE NIH
COUNCILS.
JOHN IS GOING TO FORMALLY
WELCOME OUR NEW MEMBERS AND
ACKNOWLEDGE THE CONTRIBUTIONS OF
THOSE WHO ARE ROUGH ATOM
PARTICIPATE ROTATION
OFFICEITATING OFF IN JUST A FEW
MINUTES DURING HIS GENERAL
UPDATE.
AFTER THAT WE ARE LUCKY ENOUGH
TO HAVE A PRESENTATION BY
DR. MALA MURTHY, ON THE FLY
PROGRAM WHERE SHE MAPPED THE
ENTIRE BRAIN OF DROSOPHILA AND
THIS IS QUITE AN ACCOMPLISHMENT
AND WE ARE LUCKY ENOUGH TO HEAR
MORE ABOUT THIS LATER TODAY.
FOLLOWING THE OPENING SESSION,
WE WILL HAVE A BREAK AND DURING
THE CLOSED SESSION I WILL GO
OVER A FEW OPERATING PROCEDURES.
WE EXPECT THAT TO START AROUND
2:30 P.M. THERE ARE DIFFERENT
TEAMS LINKS FOR THE OPEN AND
CLOSED SESSION.
ALSO AS YOU KNOW, AS YOU
NOTICED, WE ARE USING TEAMS AND
NOT ZOOM, SO WE ARE HOPING THAT
EVERYTHING WILL RUN SMOOTHLY BUT
THIS IS NEW TO MOST OF US FOR
THIS KIND OF A MEETING SO PLEASE
BEAR WITH US.
FEW HOUSEKEEPING ITEMS, WE ASK
THAT YOU MUTE YOUR LINE DURING
PRESENTATIONS OR DURING -- OR
WHEN OTHER PEOPLE ARE SPEAKING
DURING THE DISCUSSION, WE WILL
LIKE ON YOU TO PUT YOUR VIDEO ON
AND USE THE RAISES HAND OPTION
IF WE HAVE QUESTIONS AND THEN WE
WILL CALL ON YOU TO UNMUTE
YOURSELF AND AGAIN, BECAUSE THIS
IS AN OPEN SESSION, IT'S BEING
VIDEOCAST, WE PREFER YOU NOT TO
USE THE CHAT FUNCTION FOR
DISCUSSIONS SINCE THAT WOULD NOT
BE VISIBLE THROUGH THE
VIDEOCAST.
FINALLY, I WANT TO THANK THE
OUTSTANDING TEAM WHOSE HARD WORK
WENT INTO PREPARING FOR THIS
MEETING, IN PARTICULAR
DR. CRYSTAL LANCE WHO HAS TAKEN
OVER FOR DR. KRISTIN DUPREE, WHO
IS UNFORTUNATELY IS NO LONGER
WITH THE INSTITUTE.
DR. NINA, SHOO, MISS DEBFREENER
AND DEBPEARSON WHO ARE
OUTSTANDING COLLEAGUES WHO DO A
WHOLE LOT OF WORK BEHIND THE
SCENES TO MAKE THIS HAPPEN AND
THEY ARE BOTH EXTREMELY
EFFECTIVE AND VERY PLEASANT TO
WORK WITH AS I'M SURE YOU KNOW
IF YOU ALREADY WORKED WITH THEM.
AT THIS POINT, I AM GOING TO
TURN IT OVER TO JOHN.
>> THANKS, SUSAN, THANK YOU FOR
THAT, GREAT TO SEE EVERYBODY
HERE AND BIG THANKS TO THE FOLKS
THAT MADE THIS HAPPEN, MICHELLE,
CRYSTAL, NINNA AND DEB.
COULD NOT DO THIS WITHOUT YOU
AND OF COURSE WE MISS KRISTIN
DUPREE, BUT SHE HELPED US GET TO
WHERE WE ARE, WORKING WITH THE
THING THROUGH TEAMS, THE
TRANSITION, I THINK WE SRO IT
WORKED OUT BUT WE'VE DONE MANY,
MANY DRY RUNS BUT IF WE RUN INTO
GLITCHES, JUST HAVE PATIENCE, WE
WILL GET THROUGH T. SO I WILL
LIKE TO GIVE UPDATES, WHICH IS
BECAUSE OF VARIOUS, ISS, WAS A
WHILE AGO, WE MISSED OUR JANUARY
MEETING AS YOU KNOW, BUT I WOULD
LIKE TO SHARE WITH YOU THE
THINGS WE AND YOU ALL HAVE BEEN
UP TO AND THEN SUSAN MENTIONED
WE HAVE A REAL TREAT, TALK FROM
OUR OWN MEMBER MALA MURTHY, FROM
BRAIN WIRING TO BEHAVIOR IN
DROSOPHILA, THAT'S A REAL TREAT
COMES UP FOR US, SO LET'S SEE,
CAN I DO THIS?
OKAY, CAN YOU SEE SOME OF WHAT
IT LOOKS LIKE WE SHOULD BE
SHOWING YOU?
ARE WE GOOD?
I CAN'T SEE ANYBODY, I'M
ASSUMING WE'RE GOOD.
SUSAN ARE WE GOOD?
JUST BLINK ONCE.
>> WE'RE GOOD, WE'RE GOOD.
SORRY!
>> OKAY.
SO HERE'S MY UPDATE FOR YOU
TODAY ON MAY EIGHTH.
AS SUSAN MENTIONED WE HAVE 3
MEMBERS CYCLING, OFF TARYN
REPRESENTING NIH, TARA,
REPRESENTING NEI AND BRIAN
REPRESENTING NG RA, WE HAVE BEEN
APPRECIATIVE TO HAVE YOU WITH
US, APPRECIATE YOUR INPUT, GOOD
HUMOR AND GRACE IN HELPING US
MAKE THIS PROGRAM WHAT IT IS.
AND THEN SUSAN ALSO MENTIONED WE
HAVE A FEW MEMBERS COMING ON,
DELIGHTED TO WELCOME EDDIE CHANG
TO THE GROUP, I DON'T KNOW IF
HE'S HERE BUT IN ANY CASE, CHAIR
OF SURGERY AT UCSF, HE DIRECTS
THE JOINT UCSF, UC BERKELEY FOR
SHARING AND PROSTHESIS, HE'S A
NEUROSURGEON WHO SECIALIZES IN
THE TREATMENT OF EPILEPSYS,
GENERAL NEUROLOGY AND BRAIN
TUMORS AND I THINK YOU'VE SEEN
SOME OF HIS BRILLIANT WORK ON
BRAIN MACHINE INTERFACES AND
ALSO IN OTHER ASPECTS USING
INVASIVE NEURAL PROCEDURES.
SO IT'S REALLY A DELIGHT TO HAVE
EDDIE ON BOARD WITH US WITH THE
BRAIN INITIATIVE.
ALSO DELIGHTED TO WELCOME A GOOD
FRIEND AND BOLD CLEGLY CHAN LO
FROM STANFORD UNIVERSITY.
LEE CHAN IS THE ANN AND BILL
SWINDELL'S PROFESSOR IN THE
SCHOOL OF HUMANITIES AND
SCIENCES, PROFESSOR OF BIOLOGY,
NEUROBIOLOGY AT STANFORD.
HE'S BEEN A HOWARD HUGHES
MEDICAL INVESTIGATOR FOR MANY,
MANY YEARS, HE'S PIONEERED FROM
THE POST DOC WITH GEN COLLAB,
HE'S PIONEERED TOOLS FOR
DISSECTING NEURAL CIRCUITS IN
MAMMALS AND IT'S LED TO CIRCUIT
BASES OF BEHAVIOR AS WELL AS IN
DEVELOPMENT SO THIS IS A GREAT
EMBODIMENT OF HOW TECHNOLOGY CAN
REALLY ACCELERATE DISCOVERY AND
SOME OF YOU MAY KNOW, LIQUN AS
THE PRINCIPALS OF NEUROBIOLOGY,
IT'S A GREAT TEXTBOOK FOR
UNDERGRADUATES AND BEYOND AS
WELL AS GRAD STUDENTS AND I
REMEMBER WHEN HE FIRST PUBLISHED
THIS BOOK, IT WAS A BIT OF A
QUANDARY WHEN I WAS TEACHING
INTRA DUCTORY NEUROBIOLOGY
BECAUSE I HAD TO REFORM SOME OF
MY LECTURES BECAUSE IT WAS JUST
A BETTER BOOK THAN WHAT WE WERE
USING BEFORE BUT IT WAS A GREAT
OPPORTUNITY FOR ALL OF US TO UP
OUR TEACHING GRAIM AND LIQUN,
REALLY APPRECIATE YOU FOR THAT.
I THINK YOU'RE ON THE SECOND OR
THIRD EDITION IF I'M NOT
MISTAKEN AND THEN DR. RSOTO, AND
IMMUNOLOGY AND NEUROSCIENCE AT
BAYLOR COLLEGE OF MEDICINE,
DIRECTS THE EDUCATION DIRECTOR
OF EDUCATION OF THE DUNCAN
NEUROLOGICAL RESEARCH INSTITUTE,
COMMITMENT AND GRADUATE
DEVELOPMENT WHICH WHICH WE ALL
APPRECIATE AND THIS IS REFLECTED
IN RECEIVING THE 2021 NINDS
AWARD FOR OUTSTANDING MENTORSHIP
AND HIS RESEARCH IS MOUSE MODELS
AND NOT TO MENTION THE
CEREBELLUM DISEASE AND OTHER
RELATED DISORDERS AND THEN OUR
NEW MEMBER ISED TODD CONSTABLEO
IS AT YALE UNIVERSITY, CO
DIRECTS MRI RESEARCH CENTER AND
HIS RESEARCH FOCUS ON USES
FUNCTIONAL MAG NEDRAIC IMAGING
TO MAP THE BRAIN AND TO
UNDERSTAND THE RELATIONSHIP
BETWEEN THIS ORGANIZATION AND
BEHAVIOR, AND IS REALLY BEEN
FOCUSING ON ENGINEERING EXPOSURE
TO RADIATIONS TO DEVELOP
NOVARTIS WILL AMERICAS RI
DEVICES INCLUDING POINT OF FIELD
MRIs AND THE POETIC TEBTIAL TO
MAKE MRI MORE ACCESSIBLE AND
THIS IS 1 OF OUR ETHICS STUDIES
AND THIS IS JUST OUR GROUP OF
MEMBERS AND I THANK YOU ALL FOR
YOUR DEDICATION, YOUR
WILLINGNESS TO TICK WITH US AND
TO BE TOLERANT OF MY QUESTIONS
AND ASKS AND I THINK IT'S ALL
HELP MAKE THE INITIATIVE WHAT IT
IS TODAY NOW NOTHING WOULD
HAPPEN WITHOUT OUR INCREDIBLE
STAFF WITHIN NIH AND WE ORGANIZE
THE STAFF INTO TEAMS AND THIS IS
OUR GROUP AND I WANT TO POINT
OUT WE HAVE 2 TEAM COLLEAGUES
WHO NOW ON LEADS THE TEAM
E-GROUP THAT OVERSEES INTEGRATED
APPROACHES AND DR. JOE
MONICO
WHO HELPS MAKE THIS HAPPENS,
THERE'S WELL OVER 130 FOLKS, I
WILL JUST TELL YOU RIGHT NOW,
THIS SLIDE WAS MADE BACK IN
JANUARY OF 2025.
MANY OF THESE FOLKS ARE NOT WITH
US BUT THEIR EFFORTS AND THEIR
IMPACT ARE TILL WITH US AND I
JUST WANT TOK KNOWLEDGE ALL
THEIR GREAT CONTRIBUTIONS AND
THOSE OF US WHO ARE LEFT ARE
WORKING HARD TO MAKE SURE ALL
THIS WORK CAN STILL HAPPEN.
SO NOW, REALLY GREAT NEWS, WE
HAVE NICE RECOGNITION OF PEOPLE
IN THE BRAIN UNIVERSE AS IT
WERE, THE INSTITUTE FOR
NEUROLOGICAL AND IMAGING, ANIB,
ELECTORRED THEIR INDUCTEES IN
LATE FEBRUARY, AMONG THEM IS OUR
OWN DR. GRACE WONG WHO IS A
PROGRAM OFFICER AT NINDS AND SHE
CARRIES A LOT OF THE BRAIN FORT
FORT FOLIO AS WELL TO 2 OTHER
INVESTIGATIONS DR. CHRIS ROZELL,
AND DR. MARYAMSPAY SHANECHI, AND
DELIGHTED TO SAY THAT ALL THESE
FOLK VS COME ALONG IN THEIR
SCIENCE WITH THE BRAIN
INITIATIVE AND IT'S GREAT TO SEE
THE RECOGNITION OF THEIR AMAZING
ACCOMPLISHMENTS AND
CONTRIBUTIONS AND THEN WOB OF
OUR VERY OWN TONYA PASTER KNACK
WAS JUST AWARDED VISION SCIENCES
ASSOCIATE LIFETIME ACHIEVEMENT
AWARD TO HER CONTRIBUTIONS TO
VISION SCIENCE OVER HERE CAREER,
RECOGNIZING HER COMPELLING
RESEARCH ACHIEVEMENTS,
INTELLECTUAL LEADERSHIP AND
DEDICATED SERVICE TO THE
SCIENTIFIC COMMUNITY AND I THINK
YOU ALL SEE THAT IN THE SCIENCE
WE SUPPORT, TONYA IS A SENIOR
GRANTS OFFICER OVERSEEING REVIEW
AND I THINK YOU CAN -- I HOPE
YOU ALL AGREE THAT WE ARE
FINDING GREAT SCIENCE IN NO
SMALL PART BECAUSE OF TANIA'S
CONTRIBUTION IN BRAIN.
AND THEN FINALLY I'M DELIGHTED
TO SAY OUR OWN ANDREW MITCHENER
DEPUTY DIRECTOR OF BRAIN HAS
BEEN RECEIPTLY BEEN NAMED ACTING
DREAMTOR OF NATIONAL INTUITYS OF
MENTAL HEALTH 1 OF OUR MAJOR
FUNDERS IN THIS EFFORT.
ANDREA HAS BEEN WITH THE NIH
SINCE 2004 AND SHE WAS WITH THE
BRAIN INITIATIVE SINCE ITS
INCEPTION.
IN FACT, ANDREA WAS THE PROGRAM
OFFICER FOR THE INITIAL ROUND IN
THE BRAIN CELL CENSUS PROGRAM,
THE BRAIN INITIATIVE CELL CENSUS
CONSORTIUM AND SHE WAS MY
PROGRAM OFFICER SO I'M DELIGHTED
ALL THIS COME FIRST CIRCLE
HOPEFULLY WE WILL HAVE A
PERMANENT NIMH DIRECTOR
INSTALLED ONCE THE RESEARCH GETS
UNDERWAY IN THE MEAN TIME NIMH
IS DRIVING AND NIH THRIVING AND
WE APPRECIATE HER LEADERSHIP AND
STEPPING INTO THE NEW ROLE AS WE
GO THROUGH THESE TRANSITIONS.
AND THEN FINALLY, RECENTLY THE
NATIONAL ACADEMY OF SCIENCES HAS
ELECTED NEW MEMBERS AND THIS IS
IN RECOGNITION FOR GREAT
CONTRIBUTIONS TO SCIENCE AND
AMONG THESE FOLKS WAS 3 BRAIN
FUNDED INVESTIGATORS, DR. PAULO
ARLOTTA, WHO IS BEEN A PIONEER
AT LOOKING AT WAYS OF BRAIN
DEVELOPMENT INCLUDING THROUGH
ORGANOIDS WHICH IS REALLY A HOT
AREA.
EDDIE CHANG I JUST MENTIONED TO
YOU FROM UCSF AND ADRIAN HALL AT
WASHINGTON UNIVERSITY FOR HER
CONTRIBUTIONS TOWARD APPROACHES
TO BEDDING SYSTEMS LEVEL
APPROACHES.
SO VERY, VERY THRIFULLED THAT
OUR INVESTIGATORS WE'VE BEEN
SUPPORTED HAVE BEEN RECOGNIZED
FOR THEIR CONTRIBUTIONS.
SO I JUST WANT TO GO THROUGH A
LITTLE BIT QUICKLY, BRAIN BY THE
NUMBERS.
BRAIN CONTINUES TO BE QUITE
PRODUCTIVE.
WE'VE FUNDED ALMOST 1800 PIs
THROUGH ALMOST 1600 AWARDS.
WE'RE STARTING TO FILL IN FROM
THE COAST, THERE'S STILL A BIAS
TOWARD THE EAST AND WEST COAST
BUT WE'RE GETTING MORE IN THE
SOUTHWEST, STILL CONTAINING
ROBUSTS PUBLICATIONS THAT ARE
WIDE DIVERSITY OF JOURNALS AND
WE'RE HAPPY FOR THAT AND WE LOOK
FORWARD TO CONTINUING PROGRESS.
NOW I GUESS THE TOP OF
EVERYBODY'S MIND IS BUJ ELT NOT
JUST FOR BRAIN BUT NIH
GENERALLY.
I CAN JUST SPEAK TO WHAT WE KNOW
ABOUT THE BRAIN BUDGET RIGHT
NOW.
BRAIN FUNDING COMES FROM 2
SOURCES, BASE FUNDING TO THE 10
PARTICIPATING INSTITUTES OR
CENTERS ICDs, SHOWN IN BLUE,
THAT IS WRITTEN STEADILY THROUGH
THE YEARS UP THROUGH 2022 AND
THROUGH THE 21st CENTURY CURES
ACT WE STARTED RECEIVING MONEY
IN 2017 OF VARYING AMOUNTS TO
SUPPLEMENT THE BASE FUNDING.
THAT MONEY EVENTUALLY WILL GO
AWAY IN 2026 BUT YOU WILL NOTICE
THIS JUMP IN THE RED BAR FROM
2022 TO 2023, WHERE THE CURES
AUTHORIZATION JUMPED FROM
142 MILLION TO 450 MILLION AND
TO KEEP OUR BUDGET WITHIN A
REASONABLE RANGE A DECISION WAS
MADE TO TRIM OUR BASE FROM
468 MILLION IN 2022, TO
230 MILLION IN 2023, SO WE
ACTUALLY GOT AN OVERALL
60 MILLION-DOLLAR INCREASE,
ALMOST 10% INCREASE FROM
2022-2023 BUT AS WE PROGRESSED
INTO 2024 THE BASE STAYED LEVEL
AND THE CURES ACT FUNDS, THE
AUTHORIZATION WAS PRESCRIBED TO
DROP DOWN TO 172 MILLION SO
THAT'S HOW WE LANDED AT
402 MILLION IF 2024, AND THEN
THE CONTINUING RESOLUTION, THE
BASE FUNDING STAYS FLAT WHICH IS
230, BUT AGAIN THE CURES FUNDS
DROPPED ANOTHER 81 MILLION TO 91
SO NOW WE'RE AT $321 MILLION FOR
FY25.
SO WE'RE MAKING THE BEST OF IT.
WE STILL HAVE A LOT OF GREAT
SCIENCE WE ARE FUNDING, JUST A
LITTLE BIT LESS THAN WE MIGHT
HAVE WITH MORE FUNDS, BUT AGAIN,
WE ARE COMMITTED TO FUNDING THE
BEST SCIENCE OUT THERE AND WHAT
FY26 HAS TO HOLD FOR US, WE JUST
DON'T KNOW.
YOU CAN STAY UP TO DATE WITH
WHAT WE DO KNOW BY GOING TO OUR
WEBSITE AT THESE PARTICULAR
PAGES.
YOU CAN SCAN THESE QR CODES OR
MORE DIRECTLY GO TO THE WEBSITE,
IT'S PRETTY CLEAR, THERE'S A TAB
THAT SAYS FUNDING AND THAT'S
WHERE THIS INFORMATION IS.
OKAY, SO SINCE WE LAST MET LAST
SUMMER OR FALL, WE'VE BEEN UP TO
A FEW THINGS, SFN HAPPENED,
SOCIETY FOR NEUROSCIENCE ANNUAL
ME MEETING HAPPENED AND WE WERE
DELIGHTED TO BE PART OF THE TOOL
MAKERS SATELLITE EVENT THAT'S
PROMOTED BY THE BRAIN INITIATIVE
INITTATIVE
FOR THE ALLIANCE, THIS IS WHERE
WE INVITE INVESTIGATORS TO SHOW
THEIR WEARS.
WE HAD 22 TOOLS SHOWN BY 52 TOOL
MAKERS, I THINK THERE WERE 365
ATTENDEES, REALLY WELL ATTENDED
EVENT.
HOPEFULLY PEOPLE WILL HAVE A
USE, THIS IS A WAY TO PICK UP
NEW TOOLS, GET NEW IDEAS AND
EVEN FORGE NEW COLLABORATIONS
AND WE'RE VERY, VERY EXCITED
ABOUT THAT.
ALSO LAST NOVEMBER, WE SPONSORED
A NEUROAI WORKSHOP FROM
NOVEMBER 12th AND 13th.
CAN YOU FIND ALL THIS ON THE WEB
AND THIS IS TO LOOK AT
CONVERGENCE BETWEEN NEUROSCIENCE
AND AI AND HOW WE CAN DRIVE
RECIPROCAL ADVANCES IN
UNDERSTANDING NATURAL
INTELLIGENCE AS WELL AS MACHINE
INTEL VENS.
INTELLIGENCE.
THE WORKSHOP EXPLORED DIVERSE
ELEMENTS AND CONTRASTS WITH AI'S
RELIANCE ON MORE STATIC MODELS.
WE TOUCHED ON THE POTENTIAL OF
NEUROMORPHIC COMPUTING BASICALLY
DESIGNING PLATFORMS BASED ON
WHAT WE UNDERSTAND ABOUT HOW
BIOLOGICAL CIRCUITS WORK AND HOW
WE MIGHT APPLY THOSE IN
BIOMEDICINE AND VERY EXCITING 3,
WE'RE LOOKING AT THE POSSIBILITY
OF LEVERAGING LARGE SCALE BRAIN
DATA WHICH WE ARE DEVELOPING AS
WE SPEAK, OPEN SCIENCE ACROSS
AGENCY COLLABORATIONS AND
COLLABORATIONS THAT INTEREST YOU
AS WELL, TO INSURE THAT WE HAVE
-- WE'RE CONSIDERING IN A
PROACTIVE WAY THE ETHICAL
FRAMEWORKS FOR GUIDING FUTURE
DEVELOPMENTS.
SO WE -- THE WORKSHOP ATTENDEES
HELP TO IDENTIFY PRIORITIES THAT
BALANCE INNOVATION WITH RIGOR.
WHAT ARE THE BIG WEB CONNECTEDS
THAT WE WE MIGHT ADDRESS AND HOW
TO ENABLE SCALE TO ACHIEVE
HEALTH BENEFITS IN ADVANCED
NEUROTECHNOLOGIES AND I THINK
THERE MAY BE GREAT BENEFITS THAT
GO EVEN BEYOND THE HEALTHCARE
REALM AT THE NEUROSCIENCE
REMETABOLISM.
SO THEY'RE VERY EXCITING, IT'S
SOMETHING WE'RE CLEARLY THINKING
ABOUT, IT'S A VERY, VERY HOT
FIELD BUT EVOLVING, FOR I WOULD
SAY, EVOLVING VERY, VERY
RAPIDLY, YOU COULD LEARN MORE
ABOUT WHAT WE FOUND AT THE
WORKSHOP AT THESE SITES.
THERE'S VIDEOCAST, IT'S A LOT TO
WATCH, BUT WE DO HAVE SOME
SUMMARIES YOU MIGHT FIND TO BE
QUITE USEFUL AND FINALLY, AROUND
THE TIME OF SFN, I PUBLISHED A
SHORT PIECE ON BRAINS FIRST 10
YEARS, WHAT THE INITIATIVE HAS
ACCOMPLISHED WITH INPUT AND
DISCOVERIES AND A LOT OF HARD
WORK FROM YOU ALL HERE, AND WITH
AN EYE TOWARD WHAT MIGHT BE COME
NOTHING THE FUTURE BASED ON THE
FIRST 10 YEARS.
SO IT'S A PRETTY QUICK READ, I
INVITE TO YOU COME TAKE A LOOK
AT IT.
OKAY, SO NOW I HAVE A FEW
PROGRAM UPDATES.
THERE'S BEEN A BIT OF CHURN IN
NOTICES OF FUNDING OPPORTUNITIES
OR NOFOs, YOU CAN STAY UP TO
DATE BY GOING TO OUR WEBSITE
HERE.
WE KEEP THIS UP TO DATE AND YOU
CAN USE THE QR CODE OR GO TO
THAT SITE THAT'S LISTED BELOW.
I WANT TO DRAW YOUR ATTENTION TO
1 ACTIVE NOFO, IT IS ACTIVE.
I JUST CHECKED ABOUT AN HOUR
AGO, THIS IS TO PROMOTE HEALTH
THROUGH ALL THROUGH BRAIN
TECHNOLOGY PARTNERSHIPS.
SO BRAIN INITIATIVE RIGHT NOW IS
SUPPORTING THE DEVELOPMENT OF
NEW TOOLS AND RESOURCES, WE HAVE
THE SO CALLED G24 GRANDS THAT
BEFORE DISSEMINATION TO GET
THESE TOOLS OUT THERE, AND 1
CHALLENGE IS TO GET THESE TOOLS
INTO ABOUT THE HANDS OF
RESEARCHERS AT WHAT WE CALL
RESOURCE LIMITED INSTITUTIONS.
SO MANY, MANY PEOPLE ALREADY USE
THESE TOOLS BUT WE'RE CONCERNED
ABOUT IS REALLY TRULY
DEMOCRATIZING THE TOOLS AND
TECHNOLOGIES THAT ARE DEVELOPED
BY BRAIN FOR THE BENEFIT OF ALL.
SO THE IDEA HERE IS FOLKS CAN
COME IN, WITH A GRANT
APPLICATION, LOOKING FOR FUNDING
TO TRANSFER THIS KNOWLEDGE OR
THESE TOOLS INTO A LAB AT A
RESOURCE LIMITED INSTITUTION AS
DEFINED AS THE INNS TUITION
RECEIVING LESS THAN 7 AND HALF
MILLION DOLLARS IN TOTAL COST
FOR THE LAST SEVERAL YEARS.
COUPLE REQUIREMENTS 1 IS THAT
THE CONTACT PI MUST BE AT THE
RESOURCE LIMITED INFORMATION NOT
AT THE RO-1, THAT WELL RESOURCE
UNIVERSITY AND THEN THE KEY
PERSONNEL NEEDS TO INCLUDE THE
FOLKS THAT ARE ACTUALLY
PROVIDING THE VALIDATED
TECHNOLOGY, SO, IT'S A NEW
PROGRAM.
WE HAVE A DUE DATE COMES UP ON
JUNE 17th OF THIS YEAR AND
JUNE 17th OF NEXT YEAR, THE
OTHER CRITERIA LISTED BELOW AND
IF YOU HAVE ANY QUESTIONS, YOU
CAN SCAN THE QR CODE, GO TO THE
PAGE, DR. NATALIE TRZCINSEE IS
HANDLING THIS AND YOU CAN SEE
HERE INNO AT THE BOTTOM.
HOPEFULLY WE CAN GET THIS INTO
MORE HANDS TO PUSH THE FIELD
FORWARD.
SO JUST A BRIEF SUMMARY OF COOL
THINGS GOING ON SINCE WE LAST
SPOKE.
I ALLUDED TO THIS VERY QUICKLY
BEFORE.
THIS IS JUST A VERY BRIEF
SYNOPSIS OF A SUBLICATION FROM
FRANCIS CHAN 1 OF OUR GRANTEES
IN THE BRAIN NEUROETHICS
PORTFOLIO.
NOW WE FOCUS A LOT ON DEVELOPING
THE LATEST AND GREATEST, COOLEST
MOST POWERFUL TECHNOLOGIES IN
VARIOUS DOMAINS INCLUDING
NONINVASIVE HUMAN IMAGING AND
THAT'S GREAT BUT THEN AGAIN THE
ISSUE IS HOW DO WE GET THIS SIS
SEMESTERINATED OUT TO FOLKS THAT
NEED IT.
PURHAPPENS RURAL SETTINGS SO
THEY'RE UNDERSERVED OR DISTANT
FROM THE MAJOR MEDICAL CENTERS,
SO WHAT'S COME UP, WHAT'S COME
UP AND I THINK TODD CONSTABLE
CAN SPEAK TO THIS HAS WELL IS
THE CONCEPT OF DEVELOPING
PORTABLE MRI MACHINES TO EXPAND
THIS POSSIBILITY TO THE BENEFIT
OF PATIENTS WHERE THEY WOULDN'T
OTHERWISE HAVE ACCESS TO IT BUT
IT ALSO INTRODUCES NOVEL
FEATURES INCLUDING NEW USERS,
LOCATIONS, PARTICIPANT POP
OWLINGSS, INCREASED IMAGE
QUALITY, WE DON'T WANT TO JUST
SHIP OUT LESSER TECHNOLOGY, WE
WANT FOLKS TO HAVE ACCESS TO THE
BEST AND HOW DO WE -- HOW DO WE
DEAL WITH THAT AS AN EMERGING
ISSUE.
SO DR. SHEN AND COLLEAGUES AT
THE UNIVERSITY OF MINNESOTA,
THEY IDENTIFIED 15 CORE
CHALLENGES TO BE CONSIDERED AND
DEVELOPED OPERATIONAL GUIDANCE
AND PRACTICAL TOOLS INCLUDING A
NEUROETHICS CHECK LIST, SO IT'S
SOMETHING TO THINK ABOUT AS THEY
MOVE FORWARD AND PROVIDES A
CRITICAL STARTING POINT, IT'S
NOT THE END OF THE STORY BUT
IT'S THE STARTING POINT FOR
RESEARCHERS WHO WISH TO CONDUCT
RESEARCH USING PORTAL
TECHNOLOGIES OUTSIDE OF THE
TRADITIONAL LARGE MEDICAL CENTER
OR LARGE UNIVERSITY SETTINGS
THAT PROVIDE A STARTING POINT
FOR AN INSTITUTIONAL REVIEW
BOARDS, THE COMMUNITY LEADERS,
AS WELL AS FOR THE PRIVATE
SECTOR, NEUROTECHNOLOGY
COMPANIES THAT HOPEFULLY WILL
CONTINUE TO DEVELOP THE NEXT
GENERATION PORTABLE MR TOOLS FOR
USE IN THESE DIFFERENT SETTINGS
SO I ENCOURAGE YOU TO TAKE A
LOOK AT THAT.
I DON'T HAVE A QR CODE BUT YOU
CAN LOOK IT UP IN THIS JOURNAL.
OKAY.
A LOT OF WORK GOING ON IN THE
CELL CENSUS PROGRAM, WE'RE
REALLY THRILL THAD LAST YEAR WAS
LAUNCHED FROM THE BRAIN
INITIATIVE CELL ATLAS NETWORK,
THIS BRAIN KNOWLEDGE PLATFORM
WHICH HAS JUST A TON, A TON OF
DATA AND A GROWING SET OF DATA
FROM THE BI CAN RELEASES AND
OPACCESS DATA AND IT'S GREAT
ACCESS AND TOOLS TO LOOK AT AND
USE IT TO DRIVE THEIR OWN
RESEARCH FORWARD AND AGAIN THIS
FITS WITHIN BRAIN'S ETHOS OF
SUPPORTING OPEN SCIENCE FOR THE
BENEFIT OF AS MANY PEOPLE AS WE
CAN.
ALSO COMING OUT BASED ON THE
FOUNDATION THE BRAIN CELL CENSUS
PROGRAM IS THE -- IS WORKING THE
ALZHEIMER'S RESEARCH SPACE,
USING HIGH QUALITY BRAIN DONOR
-- DONORS FOR A LARGE COHORT
SPANNING FROM LATE STAGES TO
ALZHEIMER'S DISEASE, THIS COMES
FROM THE SEATTLE ALZHEIMER'S
DISEASE BRAIN CELL ATLAS GROUP.
IT'S BEING LED BY DR. ED LEAN
AND @AL AN INSTITUTE AND IT'S
BEEN ENABLED BY MANY TOOLS THAT
CAME OUT OF THE BRAIN
INITIATIVES NETWORK AND DR. LANE
HAS BEEN WORKING ON THESE TOOLS,
IT HAS A DEEP CLINICAL
PHENOTYPES AND THEY FOUND SOME
UNEXPECTED THINGS THAT MIGHT BE
POTENTIALLY RELEVANT AND USEFUL
IN TERMS OF THERAPEUTIC TARGETS
AND FROM THESE ANALYSIS, WHAT
THEY FOUND IS THEY COULD DIVIDE
THE PROGRESSION OF DISEASE INTO
AN EARLY OR QUIET PHASE AND A
LATER RAPIDLY PROGRESSING
SYMPTOMATIC PHASE AND DURING
THIS EARLY QUIET PHASE THEY
FOUND THE SELECTIVE DEATH OF A
SELECTIVE CLASS OF SOPHISTICATED
MATOSTATIN INHIBITORY NEURONS
AND AS WELL AS CHANGES IN OTHER
NONNEURONAL CELLS AND THIS MIGHT
BE AN IDEA EARLY IN THE PROCESS
AND PERHAPS GIVE US A WAY TO
HAVE INTERVENING, SLOWING OR
EVEN PREVENTING DISEASE
PROGRESSION.
AND AGAIN, WITHIN THE ETHOS OF
THE BRAIN INITIATIVE, THEY
PROVIDE OPEN ACCESS TOOLS AND
RESOURCES FOR THE ENTIRE
SCIENTIFIC COMMUNITY.
NOW I'M SURE MALA WILL TELL US A
LOT ABOUT THIS BUT I CAN'T HELP
BUT SHOW THIS COOL ANIMATION, SO
SORRY, MALA I WILL NOT STEAL
YOUR THUNDER, I PROMISE.
WE HAD A NUMBER OF PUBLICATIONS
FROM THE FLY WARE, SUPPORTED BY
BRAIN AND THIS RESULTED IN A
NUMBER OF PAPERS IN NATURE, AND
THESE GORGEOUS REPRESENTATIONS
THAT REPRESENT THE FIRST FULL
RESOLUTION CONNECT OHM OF AN
ADULT ANIMAL IN THIS CASE A
FEMALE DROSOPHILA.
THE GROUP MANAGED TO
CHARACTERIZE 139,000 NEURONS,
FRIEF HUNDRED UNIQUE CELL TYPES,
OVER 50 MILLION SYNAPSES,
RESULTING IN NONJOINTLICATIONS
IN NATURE, AND IN ADDITION TO
ROUGH ATOM -- PROVIDING THE
GROUND TRUTH INFORMATION AND THE
ABILITY TO CONSTRAIN HYPOTHESIS
ABOUT NEURAL CIRCUIT FUNCTION AS
THEY RELATE TO DRIVING DEHAD A
FEWS AND I'M SURE MALA WILL TALK
ABOUT THIS AT LENGTH, IT ALSO
INFORMS THE DEVELOPMENT WITH
THESE NEW TOOLS OF LARGE AND
MAMMALIAN WHOLE BRAIN CONNECT
ORDER OF MICRONSS, AND QUICKLY
THROUGH THE THINGS WE FIND TO
EFFORT, IT'S THE POWER OF
CITIZEN SCIENCE TO HELP PROOF
READ THIS AMAZING COLLECTION OF
DATA AND THE POWER OF OPEN
SCIENCE.
THE FLY WATER GROUP MADE THE
DATA AVAILABLE YEARS BEFORE THIS
PUBLICATION AND WE THINK THAT
ENABLED REALLY COOL PAPERS TO
UBIQUITINNATION PUBLISHED BASED
ON THAT DATA, VERY RICH DATA
RESOURCE WELL BEFORE THESE FOLKS
EVEN PUBLISH IT THEMSELVES.
THIS IS REALLY A TESTAMENT TO
WHAT CAN BE DONE BY SCIENCE AND
SCALE WITH THE IDEA OF LIFTING
ALL THOSE BY GENERATING THESE
OPEN RESOURCES.
AND THEN JUST A FEW WEEKS AGO,
THE MICRONS CONSORTIUM, THE
MACHINE INTELLIGENCE AND
CORTICALE NETWORKS PROJECT JUST
PUBLISHED AN AMAZING CONNECT OME
MAP OF THE VISUAL CORTEX.
I WILL SHOW THE AN MAZE HERE,
THIS IS SO COOL.
THIS A LARGER HUNK OF TISSUE
THAN A FLY BRAIN BUT REALLY
QUITE BEAUTIFUL.
AGAIN, RESULTING IN A PACKAGE OF
PUBLICATIONS IN NATURE AND
NATURE SISTER JOURNALS.
THIS IS ALSO A LARGE TEAM
EFFORT.
THIS WAS A CONSORTIUM OVER 150
RESEARCHERS FUNDED BY BOTH ARPA,
THIS IS WHERE THE PROJECT
STARTED AS A MICRONS PROJECT
FOLLOWING FUNDING FROM NIH
BRAIN. THIS IS A PROJECT THAT
WAS LED BY INVESTIGATORS FROM 3
BRAIN INSTITUTIONS, THE ALAN
INSTITUTE, PRINCETON UNIVERSITY
AND BAYLOR COLLEGE OF MEDICINE
AND TOGETHER THEY CHARACTERIZE
OVER 2 MILLION CELLS IN THE
CUBIC MILLIMETER ABOUT THE SIZE
OF A BRAIN OF RICE, 4 MILLION
AXOONS OVER 500 MILLION
SYNAPSES, REALLY COOL BUT BEFORE
THEY TOOK THIS 1 TISSUE FOR
PROCESSING, THEY PUT THE MOUSE
IN FRONT OF A VIDEO SCREEN AND
THEY SHOWED IT VARIOUS CLIPS
ANIMATED CLIPS INCLUDING
NATURALISTIC SCENES AND THEY
USING GCAP IMAGING AND THEN THEY
FIXED AND SECTIONED THROUGH THE
PIECE OF CORTEX AND THEY
RECONSTRUCTED IT AND WHAT THEY
WERE ABLE TO DO IS THEY WERE
ABLE TO OVERLAYA ACTIVITY FROM
ABOUT 76,000 NEURONS ON TO THAT
MAP.
SO THEY PROVIDED NOT JUST A
STATIC MAP BUT ALSO A WAY TO
CONNECT FUNCTIONAL RESPONSES
WITH THE ANATOMICAL MAP AND THIS
IS REALLY THE HOLY GRAIL HERE IN
THE FIELD WHICH IS TO BE ABLE TO
LOOK AT ACTIVITY ACROSS THESE
VASTLY COMPLEX NETWORKS SO
REALLY GREAT START TO THIS
FIELD.
WE'RE VERY, VERY EXCITED ABOUT
THIS.
THEY'VE AGAIN DEVELOPED AN OPEN
RESOURCE FOR DEVELOPING MODELS
OF NEURAL COMPUTATIONS, AGAIN
THE NAME OF THE GAME HERE IS
OPEN RESOURCES, AND THIS WILL
SET THE STAGE FOR THE BRAIN
CONNECTS PROJECT WHICH WE ARE
WORKING VERY ACTIVELY ON AS WE
SPEAK.
WITH THAT, IT'S GETTING TO THE
END.
YOU CAN FIND REQUESTING ON THE
WEBSITE, WE PUBLISH NOTES ON THE
BRAIN BLOG, SO CHECK-IN THERE
FROM TIME TO TIME AND GUIDE
NOTICES AND OF COURSE YOUR
ABOUTEST RESOURCE FOR THE BRAIN
IN TERMS OF FUNDING OPPORTUNITY
SYSTEM TO FIND YOUR BRAIN
PROGRAM OFFICER AND THAT'S
LISTED AS WELL ON OUR BRAIN
WEBSITE THAT YOU CAN FIND AT
BRAIN .GOV.
SO I WILL STOP THERE, SUSAN DO
WE HAVE TIME FOR A FEW QUESTIONS
BEFORE WE MOVE ON TO MALA'S
TALK.
YES, WE ACTUALLY HAVE QUITE A
BIT OF TIME.
SO, YEAH.
BRIAN?
>> BRYAN?
>> BRYAN, HIBRYAN?
>> HI, GREETINGS.
SO, 1 THING THAT WOULD BE VERY
USEFUL SOPHISTICATED TO -- MY
WIFE IS COMING IN HERE --
>> HI, BRIAN'S WIFE.
>> YOU CAN SEE SHE BROKE HER
ARM.
>> BUT YOU STILL HAVE THE DOG,
GOOD.
>> IT'S A GOOD THING.
>> SO I WAS RECENTLY GAVE A
PUBLIC TALK IN ALL PLACES,
MONTANA WHERE I WENT FOR
UNDERGRAD AND I HIGHLIGHTED THIS
AMAZING RESOURCE THAT WAS JUST
PUBLISHED IN NATURE.
IT'S TRULY ASTOUNDING BUT WHAT
I'M ASKING IS FOR -- IS IT
POSSIBLE THAT EITHER FOLKS AT
THE NIH OR PEOPLE IN THE MICRONS
COULD MAKE A SUMMARY VIDEO
THAT'S HIGH QUALITY THAT, WE
COULD SHARE, THAT SHOWS, YOU
KNOW WHAT YOU JUST SHOWED,
BASICALLY?
SO I WAS ABLE TO, YOU KNOW I
DOWNLOADED THE VIDEOS THAT THEY
HAVE AND EDITED THEM BUT IT
WASN'T QUITE WHAT I WAS LOOKING
FOR SO IT WILL BE REALLY NICE IF
THEY COULD PROVIDE SOMETHING
LIKE THAT FOR US TO USE WHEN WE
GIVE TALKS BECAUSE IT'S JUST --
I MEAN IT'S AN AMAZING
ACHIEVEMENT, FOLKS.
>> YEAH, YEAH.
>> I WOULD REALLY LIKE TO
PUBLICIZE IT.
>> YEAH, SO I PUT THAT VIDEO IN,
I WILL CONFESS, IT'S NOT THE
HIGHEST QUALITY VIDEO, I JUST
DIDN'T GET AROUND TO BOTHERING
FOLKS FOR IT BUT YOU CAN CONTACT
THE FEEMSA THE THE ALAN
INSTITUTE, THEY'VE BEEN GREAT
ABOUT SHARING THESE RESOURCES,
THANK YOU FOR GETTING THE WORD
ABOUT ABOUT THE SCIENCE ISSUES
THE MORE PEOPLE THAT KNOW ABOUT
THE RESOURCE, THE MORE PEOPLE
WILL BE USING IT SO I WILL
SUGGEST CONTACTING THEM, SINCE I
DOWNLOADED THAT 1 LITTLE CLIP IN
A VERY AMATEURISH WAY, I'M SURE
YOU CAN FIND A BETTER COPY.
MALA, MAYBE YOU CAN HELP.
>> I WILL JUST CHIME IN AND SAY
YOU SHOULD E-MAIL AMY STERLING,
SHE MAKES THE VIDEOS FOR THE
FLYWIRE AND THE MICRONS PROJECT,
SHE WILL GIVE YOU WHAT YOU NEED
SO JUST E-MAIL HER.
>> COULD YOU PUT HER E-MAIL
ADDRESS IN THE CHAT.
>> WILL DO.
>> THAT WOULD BE AWESOME AND LET
HER KNOW SHE WILL BE GETTING
SOME E-MAILS.
>> YEAH, AND WE CAN FOLLOW UP
AND DISTRIBUTE IT TO THE REST OF
THE MCWG.
>> I MEAN IT'S ASTOUNDING THANK
YOU.
>> THANKS, BRIAN YOUR BEING UP
THERE AS A GREAT AMBASSADOR FOR
THE PROGRAM.
>> OTHER QUESTIONS OR COMMENTS?
>> YEAH, I LOVE TO SEE THOSE
VIDEOS, TOO, BUT I WAS TRYING TO
CHAT THAT BUT THANK YOU.
>> YEAH IF YOU GO TO THE MICRONS
WEBSITE, IT'S THERE.
IF YOU GO TO THE LANDING PAGE ON
NATURE -- NATURE HAS A LANDING
PAGE, THERE'S A BEAUTIFUL
LANDING PAGE THERE AS WELL.
A LOT OF GREAT STUFF.
BUT YOU KNOW AGAIN, YOU SHOULD
CONTACT -- I DIDN'T WANT TO
SURVEY ME AND MYSELF AND AMY
STERLING SHE'S MADE AMAZING
PIECES THAT CAN BE USED.
WE'RE VERY EXCITED TO SEE THESE
BIG PROJECTS, I DON'T WANT TO
SAY COME TO FRUITION, THEY'VE
REACHED A POINT WHERE THEY CAN
BE USED AND DEVELOP FURTHER AND
AGAIN LONG THE WHOLE CONTINUUM
OF DEVELOPING THESE MAPS INTO
OTHER OR SIMILARLY OR EVEN MORE
COMPLEX SYSTEMS WILL BE FUN TO
WATCH OVER THE NEXT COUPLE OF
YEARS.
OKAY.
ANYBODY ELSE?
>> ANY OTHER QUESTIONS?
>> ANY QUESTIONS?
>> MORE EXCITING STUFF COMING
FROM OUR OTHER CONSORTIA, SO
KEEP OUR EYES OUT.
>> I HAVE 1 FOLLOW UP QUESTION
TO THAT ACTUALLY IF THERE'S A
MOMENT WHICH IS THAT THESE
RESOURCES SEEM REALLY FABULOUS
AND WITH THE FEES AND OTHERS
LIKE THE ALAN BRAIN PROJECT, I'M
WONDERING IF THERE ARE EXISTING
THINGS IN PLACE FOR TRAINING
COURSES AND BEING ABLE TO ACCESS
THESE RESOURCES BECAUSE THAT
WOULD BE GREAT FOR THE GROUPS I
KNOW OF.
>> RIGHT.
SO WE ARE SUPPORTING A NUMBER OF
THESE, YOU WILL HAVE TO -- LET'S
SEE HOW CAN WE MAKE THAT MORE
OBVIOUS?
ARE THEY ON OUR WEBSITE NOW?
THE FOLKS THAT ARE BEING FUNDED
FOR THESE COURSES THEY DO
ACCEPTED -- SEND OUT NOTICES
INVITING PEOPLE TO PARTAKE.
LET'S SEE.
MAYBE 1 OF MY -- 1 OF OUR GREAT
STAFF COULD TELL YOU HOW TO LOOK
FOR THAT.
CRYSTAL ARE YOU AROUND?
>> YEAH I'M ACTUALLY JUST
PULLING IT UP ON 1 OF OUR FUNDED
R25S WHICH ARE SHORT COURSES
THAT COVER SOME OF THESE
ACTIVITIES AND I WILL DROP THE
LINK IN THE CHAT.
>> SO WHERE MIGHT 1 FIND THAT ON
OUR WEBSITE?
SINCE THE CHAT DOESN'T GO OUT TO
THE VIDEOCAST.
>> YEAH, SO IF YOU GO TO OUR
WEBSITE BRAIN .GOV AND GO TO
FUNDING ON THE DROP DOWN MENU,
THERE'S A SECTION THERE THAT
SAYS STUNTED AWARDS, IF YOU
CLICK ON THAT IT WILL COME WITH
A LISTING OF ALL OF OUR FUNDED
AWARDS TO DATE AND YOU SHOULD BE
ABLE TO SEARCH R25 TO FIND
R-SHORT COURSES.
>> THANKS CRYSTAL.
THANK YOU TOR FOR BRINGING THAT
UP.
THESE ARE WAYS WE ARE TRYING TO
GET THE STUFF OUT THERE.
YEAH.
OKAY.
ANY OTHER QUESTIONS.
MALA, ARE YOU READY IN.
>> YES, I THINK SO.
WELL I'M GOING TO SAY A FEW NICE
THINGS FIRST SO HOLD ON.
>> I WILL WAIT TO SHARE MY
SCREEN.
>> YEAH, KUWAIT SO AGAIN I'M
DELIGHTED TO HAVE DR. MALA
MURTHY GIVE OUR SCIENCE TALK, WE
TRY TO HAVE A SCIENCE TALK FROM
1 OF OUR MEMBERS FROM TIME TO
TIME.
MALA IS A PROFESSOR OF
NEUROSCIENCE AT PRINCE TOLL-LIKE
RECEPTOR UNIVERSITY AND ALSO
DIRECTOR OF THE PRINCETON
NEUROSCIENCE INSTITUTE SINCE
JULY OF 22, SHE RECEIVED BATCHER
CEIVED --
BACHELOR'S DEGREE FROM M. I.T.
AND SHE RECEIVED HER Ph.D.
DOING STUFF IN THE BEGINNING OF
HER PLAYING OUT INTEREST IN
SENSORS AND NEUROSCIENCE USING
DROSOPHILA SOPILLA USE A MODEL
SYSTEM.
SHE'S DONE BRILLIANT WORK THERE.
SHE'S KNOWN FOR THE PIONEERING
WORK IN UNRALPHING THE CIRCUIT
AND COMPUTATIONAL BASIS OF
SOCIAL BEHAVIORS ISSUES SHE'S
BUILT AN INCREDIBLE GROUP OF
COMPUTATIONAL SCIENTISTS AND
EXPERIMENTALISTS USING
DISCOVERED SOME OF THE SENSORRED
FEEDBACK USE AND BRAIN INTERNAL
STATES THAT MODULATE SONG
PATTERNS IN FLIES.
LEVERAGING THE AWESOME HAD --
NOT JUST THE AWESOME POWER OF
GENETICS AND ALSO APPLYING AND
INVENTING AND APPLYING REALLY
COOL METHODS FOR QUANTIFYING
ANIMAL BEHAVIOR.
AND MANY OF THESE METHODS HAD
BEEN APPLIED MORE BROADLY ACROSS
THE FIELD, NOT JUST IN THIS 1
SYSTEM, AND AGAIN REALLY
INTEGRATING ALL OF HER WORK
THEORY.
AS MENTIONED MALA ALSO CO-LED
THE FLY WIRE CONSOWRTIUM WHICH I
JUST TOUCHED ON A FEW MINUTES
AGO.
MALA HAS RECEIVED A NUMBER OF
AWARDS, NIH INNOVATOR AWARD,
CLEAN FOUNDATION, Mc KNIGHT
SCHOLAR AWARD, NINDS RESEARCH
PROGRAM AWARD, A BUNCH OF
AWARDS, JUST THE EARN FOR THE
NIH BRAIN INITIATIVE AND YOU'VE
ALREADY SEEN WORK THAT'S FUNDED
THROUGH BRAIN TO MALA AND HER
COLLEAGUES BUT YOU MIGHT HEAR
MORE ABOUT THAT IN A MINUTE AND
ALSO AN HHMI SCHOLAR ARK WARD,
AND SCIENTIST AWARD AMONG
OTHERS.
SHE PARTICIPATED FOR SEVERAL
EVENTS FOR THE BRAIN INITIATIVE,
M ALA, I CAN'T THANK YOU FOR FOR
THAT, AND HERE SHE IS WITH THE
BRAIN WORKING GROUP SINCE 2021.
SO LOOKING FORWARD AS ALWAYS TO
HEARING AND SEEING 1 OFIOURE
TALKS.
TALKS -- 1 OF YOUR TALKS.
IT'S ALL YOURS.
>> THANK YOU JOHN.
AND THANK YOU FOR THE EXTENSIVE
INTRODUCTION, I DON'T KNOW THAT
IT WAS FULLY DESERVED BUT I
APPRECIATE IT.
LET ME SEE IF I CAN SHARE MY
SCREEN IN MS TEAMS, GIVE ME A
SECOND.
DO YOU SEE MY SCREEN?
>> LOOKS GOOD.
>> OKAY, IT'S FUZZY.
>> IS IT FUZZY TO EVERYBODY
ELSE.
>> IT'S FUZZY, AND YOU'RE
BREAKING UP A LITTLE, YOU'RE
KIND OF PIXELATED AS WELL.
>> I'M IN MY OFFICE WHICH WILL
SURPRISE ME IF I DON'T HAVE GOOD
WHYIFY.
THAT'S BETTER.
>> THAT'S PRETTY FUZZY.
>> BUT NOT YOU.
THE SLIDE IS BETTER.
>> I TOOK THE SLIDE DOWN.
NDESKTOP'S REALLY FUZZY.
>> IT'S NOT YOU.
DOES THAT LOOK BETTER?
>> NO.
>> IT WAS WORKING EARLIER?
>> IT WAS.
>> WHY DON'T YOU STOP SHARING
YOUR VIDEO, LIKE YOUR FACE
CAMERA, AND THEN PRESENT AND SEE
IF THAT WORKS.
>> OKAY.
>> DO WE HAVE A COPY OF YOUR
SLIDES, WOULD IT BE EASIER IF WE
PRESENT THEM FOR YOU.
>> LET ME TRY 1 MORE THING.
>> LET ME SEE IF I SHARE MY
WINDOW.
OKAY, DO YOU SEE THAT, DOES THAT
LOOK ANY BETTER?
>> UNFORTUNATELY, NO.
>> OKAY, MALA, YOU MAY ALSO WANT
TO TRY LOGGING OFF AND THEN
COMING BACK IN.
SOMETIMES THAT CAN HELP SOME OF
THE CONNECTIVITY ISSUES AND WE
WILL KEEP AN EYE OUT FOR YOU.
>> OKAY, I WILL DO THAT, HOLD
ON.
>> SEE YOU IN A BIT.
>> WE DIDN'T HAVE ANY ISSUES IN
THE TEST RUN JUST A HALF HOUR
AGO, DID WE?
>> NO.
NO.
>> I BLAME TEAMS.
>> I KNOW.
I THINK WE'RE ALL A LITTLE
FRUSTRATED WITH TEAMS.
I GUESS WE WILL GET USED TO IT
SINCE WE DON'T HAVE A CHOICE.
>> WE GOT USED TO ZOOM, WE WILL
GET USED TO THIS.
>> I AM BACK.
>> OKAY, YOU'RE BACK.
>> NOW WE WILL TRY 1 MORE TIME.
>> YOU'RE CLEARER.
YEAH, MUCH BETTER.
>> NO.
>> IT WAS BETTER A MINUTE AGO.
>> IT'S STILL THE SAME.
>> TRY TURNING YOUR CAMERA OFF.
>> OKAY.
I DON'T HAVE A SOLUTION.
>> BUT IT REALLY LOOKS BAD, YOU
CAN'T SEE ANYTHING.
>> CAN YOU SEND THE SLIDES OVER?
>> WOULD YOU LET US TRY TO SHARE
IT MAYBE?
>> SURE.
OKAY, HOLD IT.
>> JOHN YOU MIGHT NEED TO DO IT
BECAUSE I THINK THE SLIDES ARE
IN C-NOTE.
>> I DON'T HAVE KEY NOTE.
>> I DON'T EITHER.
LEE CHEN HAS KEY NOTE.
>> IT WAS WORKING EARLIER.
>> I HAVE KEY NOTE, I CAN TRY IF
YOU SEND IT TO ME MALA.
HOW SHOULD I SEND IT TO YOU.
IT'S QUITE LARGE.
>> YEAH, I HAVE A DROP BOX LINK,
I WILL SHARE THAT WITH YOU.
>> OKAY, I AM LOOKING FORWARD TO
YOUR TALK.
>> MAYBE CAN GIVE MALA'S TALK,
JUST KIDDING N. JUST KIDDING!
THAT?
THAT WOULD BE TOTALLY FINE WITH
ME, IF HE GAVE ME TALK.
>> OKAY.
>> IME SURE HE WILL GIVE AN EVEN
BETTER TALK.
OKAY, I DON'T HAVE YOU IN MY
AUTOFILL.
>> LUO@STANFORD.EDU.
>> OKAY.
THIS IS TEAM SCIENCE IN ACTION,
FOLKS.
>> THIS IS CRAZY.
>> ALL OF A SUDDEN THE SLIDE
LOOKS BETTER.
WHY DON'T YOU SEND IT AND WE CAN
TRY IN THE MEAN TIME.
>> IT WILL TAKE MAYBE A MINUTE
OR 2.
>> DOES THIS LOOK BETTER.
>> IT LOOKS GOOD, IT LOOKS GOOD
TONIGHT TOUCH ANYTHING WHY DON'T
YOU SEND IT TO LI CHEN AND THEN
WHEN WE GETS GOING WE CAN SWITCH
OVER.
>> I DON'T KNOW WHY I'M HAVING
AN ISSUE.
>> SOMETHING MUST BE UNSTABLE.
>> SO I HAVE ANOTHER COMPUTER I
COULD ALSO TRY JOINING FROM THIS
COMPUTER.
DO YOU WANT TO ME TRY THAT?
YOU GUYS TALK AMONGST YOURSELF.
OKAY, WHILE I E-MAIL I CHEN.
-- LI CHEN.
I SENT IT TO YOU.
I WILL TRY TO JOIN MS TEAMS FROM
HERE.
>> YOUR TALK IS HERE, I GOT IT,
I NEED TO DOWNLOAD IT.
>> I'M JUST LOOKING FOR THE LINK
TO THE MEETING TODAY, SO I CAN
JOIN ON MY OTHER COMPUTER, WHERE
IS THAT?
>> MALA, IF IT HELPS, IT'S IN
THE CHAT AS WELL, THE MEETING
INFORMATION FOR YOU TO COPY.
WE JUST POSTED IT.
>> YEAH, I TRIED TO I DIDN'T
EVEN FROM MY OTHER COMPUTER,
IT'S NOT -- IT'S NOT LETTING ME.
I GET A SIGN THAT SAYS REGISTER.
YEAH, YOU WILL NEED TO JOIN FROM
THE E-MAIL LINK THAT YOU WERE
SENT WHEN YOU REGISTERED, IT'S A
PERK OF TEAMS.
LET ME TRY.
>> I WILL JOIN FROM MY OTHER
COMPUTER, IT SAID I HAD EXCEEDED
THE NUMBER OF DEVICES.
THAT DID NOT WORK.
>> OKAY.
>> IT SHOULD BE AT THE TOP OF
YOUR INBOX AS WELL.
NLET ME TRY TO SHARE.
OKAY, TRY IT.
>> I'M NOT VERY FAMILIAR WITH
THE MICROSOFT THING EMPLOY
>> SO STRANGE.
>> I'M NOT SURE THIS WILL HELP
BUT IN MY EXPERIENCE IT DOES
MAKERS AND A DIFFERENCE IF YOU
HAVE TEAMS DOWNLOADED ON YOUR
COMPUTER OR IF YOU ARE JUST
USING IT ON THE BROWSER.
>> WELL I WAS USING ON THE
BROWSER, I DO HAVE THE
APPLICATION BUT I BEING NOT
FIGURE OUT HOW TO OPEN THIS
MEETING IN THE APP.
SO I DO HAVE MICROSOFT TEAMS, I
COULD SWITCH OVER TO THAT BUT I
DON'T KNOW HOW TO JOIN THIS
MEETING THERE.
>> IT LOOKS LIKE LI CHEN IS
BACK.
>> THANK YOU EVERYONE FOR YOUR
PATIENCE, CAN YOU SEE WE'RE
STILL NAVIGATING THIS.
EVERY MEETING IS AN ADVENTURE.
I CAN TRY 1 MORE TIME TO SHARE
MY SCREEN IN THE HOPES IT MIGHT
WORK.
BUT IT'S STILL BLURRY.
THERE MUST BE SOME REASON IT WAS
BLURRY NOW BUT IT WASN'T BEFORE.
>> IT WENT REALLY BLURRY.
HAVE YOU CLOSED OTHER
APPLICATIONS BY ANY CHANCE,
SORRY TO MAKE YOU GUYS HELP ME
TROUBLE SHOOT.
LINKING ICF CHEN IS BACK AND HE
WANTS TO TRY SHARING.
>> YOU WANT TO UNSHARE MALA.
>> YEAH, STOP SHARING.
BUT IT'S STILL BLURRY IS THAT
RIGHT?
>> YES.
>> OKAY.
>> HI, I'M BACK, I WAS DOWN
GRADED NOW I'M UPGRADED.
I'M GOING TO TRY TO SHARE.
>> YOU HAVE THE UPGRADE.
>> OKAY, TRY SHARING.
>> THAT LOOKS GOOD.
>> YEAH.
>> DO YOU SEE MY SCREEN?
>> WE CAN, IT'S VERY SHARP.
>> VERY SHARP.
OKAY.
>> IT'S SHARP, CAN YOU GET IT
INTO PRESENTATION MODE.
>> LOOKS GOOD BUT I HAVE TO
PROMPT LI CHEN TO SHARE THE
SLIDES.
>> ALL RIGHT, I WILL GO BACK.
>> WE WILL JUST WORK WITH WHAT
WE HAVE HERE.
>> OKAY, LOOKS GREAT.
>> YEAH.
OKAY.
>> YEAH, SO VERY SORRY, I DON'T
KNOW WHAT'S GOING ON, I'M IN MY
OFFICE SO I THINK THE INTERNET
AT PRINCETON SHOULD BE GOOD
ENOUGH.
>> I'M SORRY.
THIS IS OUR FIRST BIG THING WITH
TEAMS AND OBVIOUSLY IT'S
GLITCHY.
>> WELL WE WILL JUST GO AHEAD,
SO WITH NO FURTHER ADO, THANK
YOU JOHN FOR ASKING ME TO TALK
ABOUT MY SCIENCE.
I'VE BEEN A MEMBER -- I'VE BEEN
INVOLVED IN THE BRAIN INITIATIVE
I WOULD SAY FROM THE VERY
BEGINNING AND IT'S BEEN A
PLEASURE TO SERVE ON THE MCWG
FOR TD LAST FEW YEARS.
AND AS JOHN MENTIONED, A LOT OF
THE WORK I WILL TELL YOU ABOUT
HAS BEEN FUNDED BY THE BRAIN
INITIATIVE SO I'M VERY
APPRECIATIVE FOR THE SUPPORT
WE'VE HAD AND I ALSO JUST WANTED
TO START OFF SAYING THANK YOU TO
THE NIH STAFF WHO'S HERE TODAY,
WE ALL REALLY VALUE YOUR HARD
WORK AND THANKS AGAIN.
OKAY, LI, CHEN LET'S MOVE
FORWARD.
SO AS JOHN MENTIONED THERE WERE
A SERIES OF PAPERS WE PUBLISHED
LAST YEAR ON THE WIDE BRAIN
CONNECT O--METABOLIZED.
AND THIS WAS THE FIRST WHOLE
BRAIN CONNECT OME FOR
DROSOPHILA, SO I THOUGHT I WOULD
WALK YOU THROUGH WHY WE
CONNECTED, HOW WE GENERATED AND
IT HOW IT'S BEING USED AND GOING
TO BE USED AND I APOLOGIZE IN
ADVANCE LI CHEN, THERE'S A LOT
OF ANIMATIONS IN THIS SHOW BUT
JUST DO YOUR BEST TO FORWARD, SO
JUST KEEP GOING.
OKAY.
SO YEAH WHAT I WANTED TO SAY IS
THAT SORT OF THE HISTORY OF
NEUROSCIENCE AND SYSTEMS
NEUROSCIENCE IN PARTICULAR HAS
BEEN TO LINK INDIVIDUAL CELL
TYPES, SMALL CIRCUITS AND BRAIN
AREAS BEHAVIOR AND WE'VE DONE A
REALLY EXCELLENT JOB OF THAT AND
THERE'S BEEN YOU KNOW A LOT OF
WORK SUPPORTED THROUGH THE BRAIN
INITIATIVE IN THIS AREA, BUT THE
CHALLENGE WE'RE FACING AGAIN, OH
THIS WILL BE A GREAT TASK FOR
YOU LI CHEN TO FIGURE OUT WHEN I
WANT TO MOVE FORWARD, THIS IS
GREAT, YOU WILL HAVE A LOT OF
FUN, SO YOU'RE DOING A GREAT JOB
SO FAR.
SO WE KNOW THAT THESE CELL TYPE
CIRCUITS AND BRAIN AREAS ARE
EMBEDDED WITHIN A MUCH MORE
COMPLEX NETWORK AND WAWE REALLY
NEED NOW ARE WAYS TO CONNECT
THESE DISTRIBUTED MECHANISMS TOY
ABOUT HAD A FEW.
AND I WOULD SAY THE CRITICAL
THING IS FIRST FIGURING OUT THE
COMPLETE MAP AND THAT'S WHERE
CONNECT ORDER OF MICRONSICS CAN
HELP US OF WIRING AND THEN
THERE'S SORT OF THE MAJOR
CHALLENGE OF ONCE WE HAVE THE
WIRING, LINKING THEM SO THAT'S
WHAT I WANT TO SHARE WITH YOU
TODAY.
SO, MY LAB HAS BEEN USING
DROSOPHILA COMMUNICATIONS
ASPECTS AND AS JOHN MENTIONED
WE'VE BEEN TAKING THESE ARROWS
MECHANISTICALLY TRYING TO
UNDERSTAND THE COMPLEX FEEDBACK
BETWEEN MALES AND FEMALES.
SO THE SONG THE MALES PRODUCE IS
HIGHLY VARIABLE, HE NEVER SINGS
THE SAME SONG TWICE AS WE
DISCOVERED BUT THE RULES OF THE
BEHAVIOR CAN BE LEARNED BY
THINKING ABOUT THE INTERACTION
BETWEEN THESE 2 ANIMALS AND
USING THE SENSORY FEEDBACK AS A
PREDICTER ON BEHAVIOR AND WE'VE
MADE A LOT OF HEAD WAY THAT WAY.
BUT 1 THING I WILL TELL YOU
ABOUT SONG IS THAT THERE'S 2
TYPES OF SONG THE MALES SING SO
WHEN HE'S FURTHER FROM THE
FEMALE HE SINGS A SIMPLE PULSE
ONLY SONG AS CAN YOU SEE HERE
AND WHEN HE'S NEAR THE FEMALE HE
SINGS A MORE COMPLEX SONG WHERE
HE ALTERNATES BETWEEN 2 MAIN
MODES, PULSE AND SIGNS AND THESE
LONGER SEQUENCES.
YOU CAN KEEP GOING EMPLOY SO I
WANTED TO SHARE WITH YOU AN
EARLIER RESULT, PRECONNECT OME
TO MOTIVATE WHERE WE NEEDED THIS
WHOLE BRAIN CONNECT OME.
AND IN THIS SET OF EXPERIMENTS
WE WERE CATALOGING NEURAL
ACTIVITY THROUGHOUT THE BRAIN.
SO THE GOAL OF THE EXPERIMENT
WAS TO IMAGE 2-PHOTON MICROSCOPY
AT HIGH RESOLUTION, SMALL
VOLUMES OF THE BRAIN AND
PRECISELY STITCH THEM TOGETHER
IN AN ATLAS, AND IN EACH
EXPERIENCE WE WERE PRESENTING
THESE 2 TYPES OF SONG, PULSE AND
SIGN, AND LOOKING AT BRAIN
ACTIVITY AND BRAIN ACTIVITY WAS
BEING MEASURED WITH GCAMP
EXPRESSED EVERYWHERE SO HERE
IT'S REPORTED AS ROIs OR
REGIONS OF INTEREST.
YOU CAN KEEP GOING.
OKAY, SO WHEN WE MAPPED THIS
ACTIVITY, YOU KNOW 19,000 ROIs
ACROSS 33 FLIES.
WE FOUND IT SPANNED THE ENTIRETY
OF THE 3 ACCESS THAT DEFINE THE
BRAIN HERE, IT'S IN EVERY PART
OF THE BRAIN.
YOU CAN KEEP GOING.
AND IF WE CLUSTER THE ACTIVITY
INTO FUNCTIONAL RESPONSE TYPES,
HERE YOU SEE A BROKEN DOWN, THIS
RICH ACTIVITY INTO 18 TYPES, CAN
YOU KEEP GOING, AND WE MAP THEM
ACROSS THE BRAIN, YOU WILL SEE
THAT THIS ACTIVITY ACTUALLY
SPANS THE ENTIRETY OF THE BRAIN.
SO EACH 1 HASSA AUDITORY
RESPONSES AND IT'S NOT AS IF A
MONOLITHIC SIGNAL IS PROJECTED
EVERYWHERE AND THERE'S RICH
DIVERSE AND DIFFERENT ACTIVITY
IN EACH OF THESE REGIONS, CAN
YOU KEEP GOING, EVEN IN REGIONS
THAT HAVE BEEN STUDIED BY LI AND
OTHERS IS PREDOMINANTLY
OLFACTORY OR INDIVIDUAL, AND
THIS RESULT PARALLELLED OTHER
RESULTS THAT WERE COMING OUT AT
THE TIME FROM FLIES AND MICE IN
WHICH THE LENS HAD BEEN OPEN
RECORD ACTIVITY AT BRAIN SCALE
BUT OF LOCOMOTE OR ACTIVITY AND
THIS ACTIVITY WAS REALLY
EVERYWHERE AND THERE'S BEEN
OTHER RESULTS SIMILARLY.
SO THE CHALLENGE THEN IS TO
FIGURE OUT, THAT'S FINE, YOAN
MONCADAURE GOOD -- THE CHALLENGE
IS TO FIGURE OUT HOW TO ACTIVITY
SPREADS THROUGHOUT THE BRAIN BUT
MORE IMPORTANTLY WHAT IT'S DOING
THERE, HOW IS THIS BRAIN SCALE
ACTIVITY ACTUALLY USED BY THE
BRAIN TO DRIVE BEHAVIOR.
SO I WILL TELL YOU FIRST ABOUT
THE BUILDING OF A CONNECTOME IN
THE DROSOPHILA BRAIN TO COVER
THIS INFORMATION AT BRAIN SCALE
AND THEN I WILL TELL YOU A
LITTLE BIT ABOUT OUR DEVELOPMENT
OF NEURAL NETWORK MODELS TO
START TO GET AT THE FUNCTION OF
THE INDIVIDUAL CELL TYPES OF THE
BRAIN, SO THIS IS 1 TECHNIQUE TO
DO THIS SO WE CAN TART TO
DESCRIBE BRAIN CONNECTOME AND
KEEP GOING.
SO OUR PROJECT STARTED WITH A
DATA SET RELEASED BACK IN 2018
FROM GENELIA, AND THIS WAS A
WHOLE BRAIN MICROSCOPIC VOLUME,
1 FEMALE BRAIN CUT INTO 7000
SECTIONS AND THEN MILLIONS OF
IMAGES WITH THE EM SCOPE WERE
TAKEN AND GENELIA HAD ACTUALLY
KIND OF ABANDONED THIS DATA SET,
THEY THOUGHT THEY COULDN'T
ASSEMBLE IT INTO THE VOLUME AND
RECONSTRUCT IT AND SO THEY MOVED
TO TO A DIFFERENT METHOD TO
COLLECT WHAT IS CALLED THE
HEMIBRAIN OR A VIRTUAL WIRING
DIAGRAM OF A DIFFERENT FEMALE
BSM YOU IT WAS AROUND THAT TIME
THAT SEBASTIAN JOINED US AT
PRINCETON AND WE LOOKEDDA THE
THIS DATA AND WE THOUGHT WE
COULD ACTUALLY USE THE
CONVOLUTIONAL NEURONET AND OOH
PLIE IT TO THE FLY.
SO THE IDEA WAS THAT WE WOULD
ACTUAL LEE AUTOMATE THE NEURAL
CONSTRUCK, WE WOULD REASSEMBLE
THE VOLUME AND TRAIN HIS NEURAL
NETWORKS ON FLY GROUND TRUTH
DATA.
AND IT WAS AROUND THAT TIME THAT
SPAN JOINED OUR LAB AND SVEN
TOOK THIS DATA AND DEVELOPED A
PROOF READING PLATFORM SO MAYBE
IF YOU GO TO THE NEXT SLIDE, I
WILL EXPLAIN WHAT THIS IS.
SO IN THE TOP ROW HERE, CAN YOU
SEE WHAT THE AUTOMATED
RECONSTRUCTIONS FROM THAT EM
VOLUME WHICH I SHOWED YOU IN THE
VIDEO IN THE PREVIOUS SLIDE LOOK
TD LIKE.
AND IN THE BOTTOM ROW, YOU WILL
SEE WHAT THOSE RECONSTRUCTIONS
LOOK LIKE AFTER PROOF READING
AND I HOPE YOU CAN SEE THERE'S
DIFFERENCES.
THERE'S PIECES OF NEURON THAT
ARE MISSING OR THERE'S EXTRA
PIECES THAT HAVE TO BE FIXED AND
YOU KNOW I HAVE A LOT OF
EXPERIENCE WITH USING NEURAL
NETWORKING FOR EXAMPLE TO TRACK
ANIMAL BEHAVIOR, ET CETERA
SOPHISTICATED THERE WE DON'T DO
PROOF READING.
WE COLLECT HUGE DATA SETS AND WE
LET THE AUTOMATED METHODDINGS DO
THEIR WORK AND THEN, WE -- YOU
KNOW WE KIND OF AVERAGE OVER
THIS NOISE BUT IN CONNECT ORDER
OF MICRONSICS YOU CANNOT DO
THAT, IT'S AN NOF 1 AND THESE
ERRORS PROPAGATE THROUGH THE
ENTIRE NETWORK, THEY HAVE TO BE
FIXED SO IN THE RIGHT, YOU CAN
SEE A NEURON AND IA NUMBER OF
DIFFERENT USERS OF THIS PROOF
READING PLATFORM, MOST OF EDITS
THOSE ARE THE BLACK DOTS THAT
ARE HAPPENING WITHIN THE
DENDRITIC TREE BUT THERE ARE
EDITS THAT HAPPEN ELSEWHERE AND
SO SVEN DEVELOPED A SYSTEM THAT
WAS VERY STRAIGHT FORWARD TO
USE, VERY FAST, LARGE NUMBERS OF
PEOPLE COLLABORATING TOGETHER.
SO IN THE MOVIE YOU WILL SEE
THESE EDITS ARE PILING UP IN THE
GATTA -- DATA SET.
AND SO WE OPENED IT UP TO THE
ENTIRE COMMUNITY AS SOON AS WE
HAD THIS, BUT WE DID IT TO HELP
WITH THE CONNECTOME BUT WE ALSO
KNEW IT WOULD DRIVE THE SCIENCE
AND IT DID AS I WILL EXPLAIN.
SOPHISTICATEDY THAT'S PROOF
READING AND THAT'S WHAT TOOK THE
BULK OF TIME AND I'M TELLING ALL
THAT BECAUSE CONNECT OHMICS IS A
MAJOR PART OF THE RESEARCH
PORTFOLIO, I THINK IT'S VALUABLE
TO KNOW HOW THESE DATA SETS ARE
GENERATED.
IF YOU GO FORWARD, THERE'S 2
OTHER PIECES THAT HAVE TO BE
COMPLETED FOR A COMNECT OHM, 1
IS AUTOMATED SYNAPSE DETECTION,
YOU CAN SEE THAT IN THE LOWER
LEFT HAND CORNER.
WE DON'T PROOF READ THOSE
DETECTIONS SO WE USE THE
AUTOMATED DETECTION AND THAT'S
IN PART BECAUSE AT LEAST IN
DROSOPHILA WHEN 2 NEURONS
CONNECT, THEY DO SO EAEVER MANY
SYNAPTIC CONNECTIONS SO WE CAN
TOLERATE A LITTLE BIT OF ERROR
THERE, ALTHOUGH THE DETECTION IS
QUITE GOOD AND WE ALSO HAVE IN
OUR DATA SET, THIS IS WORK DONE
BY YAN AND LI CHEN'S FORMER
GRADUATE STUDENT, SO WE COULD
TELL BY LOOKING AT THE IMAGES
WHAT NEUROTRANSMITTER EACH 1
EXPRESSES AND BOTH OF THESE
PIECES OF INFORMATION ARE
ESENATIAL FOR THE CONNECTOME.
CAN YOU GO FORWARD.
THESE ARE THE MEMBERS OF THE FLY
WIRE CONSORTIUM, THEY CAME FROM
ALL OVER THE WORLD HELPING US TO
PROOF READ AND ANNOTATE THE
NEURONS.
AND AND IF YOU GO FOR, YOU WILL
SEE THE TOP OF THE LIST SO WE
KEEP TRACK OF ALL THE PAPERS
THAT USE FLY WIRE ON OUR WEBSITE
AND THIS LIST IS JUST GROWING
WEEK BY WEEK BUT YOU CAN SEE
BEFORE THIS PUBLICATION CAME OUT
THERE WERE LOTS OF PAPERS WHO
WERE USING THE DATA SO IT REALLY
DID PUSH PEOPLE WITH THE
SCIENTIFIC DISCOVERIES WITH THE
DATA.
SO I GUESS AS THE MOVIE PLAYS, I
WILL SAY 1 MORE WORD ABOUT DATA
SHARING, I THINK SORT OF THE
TRADITION FOR US IS TO KIND OF
CAREFULLY CURATE THE DATA AND AT
PUBLICATION TIME SHARE IT AND I
THINK IT WORKS WELL IF A LOT OF
CASES BUT FOR CONNECTOMICS IN A
LOT OF CASES, THERE IS A LOT OF
SCIENCE THAT HAS TO BE DONE
BEFORE THE DAILY BASIS THEA SET
IS COMPLETED AND MY OWN OPINION
IS THAT IT'S IMPORTANT TO SHARE
THIS DATA AS EARLY AS POSSIBLE.
SO AS JOHN MENTIONED THERE'S
ALMOST 140,000 NEURONS IN THIS
CONNECT OHM AND YOU WILL SEE THE
VARIOUS TYPES HERE.
THEIR CONNECTED BY OVER
50 MILLION SYNAPTIC CONNECTIONS
AND WE CAN COMPRESS THESE
NEURONS INTO ABOUT 8500 TYPES.
SO I WON'T PLAY THIS WHOLE VIDEO
BECAUSE YOU'VE HEARD SEEN IT, WE
CAN KEEP GOING.
AND I WILL EXPLAIN WHAT THOSE
CELL TYPES ARE IN JUST A MOMENT
BUT BEFORE I DO, THE DAILY BASIS
THEA HAS BEEN SHARED VIA
PLATFORM BECAUSE ALL CODE X,
CONNECTING THOSE AND THE BRAIN
CHILD OF OUR SOFTWARE ENGINEERS
AND CODEX, IS REALLY GREAT, CAN
YOU USE IT TO MAKE DISCOVERIES
USING THE DATA AND USING IT TO
GO FORWARD, THIS IS A MAP OF
WHERE AT LEAST 10 SEARCHES HAVE
OCCURRED IN CODEX, AND YOU CAN
SEE THEY TILE THE GLOBE, IF YOU
ZOOM IN, THESE DOTS ARE NOT JUST
AT UNIVERSITIES, THEY'RE
ACTUALLY ALL OVER THE PLACE, YOU
KNOW DISTRIBUTED, I'M CURIOUS TO
KNOW WHAT PEOPLE ARE USING FLY
WIRE FOR AND IT'S VERY EXCITING.
THIS BOTTOM PLOT IS A CODEX OF
USERS AND THIS IS DAILY
ACTIVITY SO YOU CAN SEE WE HAVE
SEVERAL THOUSAND USERS IN CODEX,
AND THIS DISSEMINATION AND
FUNDED RO21 AND THESE ARE PRETTY
GOOD NUMBERS FOR DISSEMINATION
OF BRAIN INITIATIVE AND WE'RE
PROUD OF THIS AND THANKS A LOT
TO ARIE FOR HIS SKILL IN SHARING
THE DAILY BASIS THEA.
D
A
T
A
.
OKAY, CAN YOU KEEP GOING.
SO OUR EFFORT HASN'T ENDED
THERE, WE'RE ADDING ARK DITIONAL
DATA SETS, WE'RE NOT ONLY WITH
CONNECTOME, BUT CONNECTOMES WITH
DROSOPHILA AND WE'VE BEEN
TEAMING UP WITH LI'S LAB TO
STUDY THE FINE SALIVA--SALIVA
CORD FOR DROSOPHILA THAT
MEDIATES THE MOTOR FUNCTIONS AND
YOU CAN SEE HERE A SET OF
ASCENDING AND DESCENDING NEURONS
THAT TRAVEL THROUGH THE NECK AND
WE'RE NEARING COMPLETION ON THIS
DATA SET AS YOU SEE AND I THINK
YOU WILL SEE OTHER DATA SETS
COMING OUT NOT ONLY FROM OUR
GROUP BUT GROUP AS THE GENELIA
ET CETERA AND WE'RE GETTING INTO
A PLACE FOR NEUROSCIENCE WHERE
WE THINK ABOUT INDIVIDUAL
VARIABILITY, WE THINK ABOUT
SPECIES VARIABILITY, ET CETERA,
IT'S QUITE EXCITING.
ALL RIGHT, WELL THE'S KEEP GOING
EMPLOY ALL RIGHT, SO I WANT TO
JUST TELL YOU A LITTLE BIT ABOUT
THE STATISTICS OF THE CONNECT
OHM AND JOHN IF WE GO OVER,
JUDGE UOF THE CUT ME OFF
WHENEVER YOU WANT, I AM HAPPY TO
STOP TALKING AT ANY POINT.
IF PEOPLE WANT TO INTERRUPT WITH
QUESTIONS THAT'S ALSO PERFECTLY
OKAY NWE'RE GOOD, WE'RE ALL
GOOD, WE'RE ALL ENJOYING THIS.
>> OKAY.
ALL RIGHT SO 1 OF THE PAPERS OF
THE CONNECTOME PACKAGE IS WE
WORKED ON THE ASPECTS AND 1
PROPERTY IS THAT IT'S A SINGLE
CONNECTED COMPONENT SO ABOUT 93%
OF ALL THE NEURONS IN THIS BRAIN
LIVE IN THIS 1 COMPONENT AND IN
THAT COMPONENT IF I START TO 1
NEURON I CAN GET TO ANY OTHER
NEURONS WITHIN 4 OR 5 HOPS.
SO THIS SAYS THAT THE NETWORK IS
HIGHLY CONNECTIVE, BUT IF YOU
KEEP GOING, THE FLY BRAIN IS
SPARSE SO THE PROBABILITY THAT
ANY 2 NEURONS ARE CONNECT SIDE
.02%, SO LOW, MUCH LORER THAN
C.ELEGANS FOR EXAMPLE BUT IT'S
HIGHLY RECURRENT SO IF A
CONNECTS TO B, THE PROBABILITY
THAT B CONNECTS BACK TO A IS
14%.
AND IN THE LAST PART OF THE
SLIDE, YOU WILL SEE THAT THE FLY
BRAIN HAS THIS VERY LARGE PART
OF NEURONS, THESE NEURONS ARE
NOT ONLY CONNECKED TO THE NEURON
BUT THEY'RE HIGHLY CONNECTED TO
EACH OTHER AND THIS IS AN
EXTREMELY LARGE NUMBER
RESPONSIBLE FOR THIS PROPERTY.
WHICH MEANS YOU CAN'T JUST PRUNE
AWAY 1 NEURON AND HAVE THE
NETWORK FALL APART, THERE'S
THOUSANDS OF THESE HUB NEURONS
THAT ARE CONNECTING EVERYTHING
TOGETHER.
WE CAN KEEP GOING.
BECAUSE OF THIS PROPERTY, IF WE
LOOK AT INFORMATION FLOW IN THE
CONNECT OHM, WE TART WITH THE
SENSORY RECEPTOR POPULATION,
LIKE THE TASTE NEURONS AND THEN
WE FOLLOW INFORMATION FLOW,
PROBABLISTICALLY THROUGHOUT THE
NETWORK WE CAN MAKE A MAP, HERE
YOU SEE A UMAP WHERE EACH DOT IN
THE UMAP IS A NEURON.
AND IT'S POSITION IN THE UMAP IS
ITS PROXIMITY TO ALL OF THE
DIFFERENT SENSORY RECEPTOR
NEURONS.
SO CAN YOU SEE AT THE BOTTOM
HERE, THE NEURONS THAT ARE
COLORED RED ARE VERY CLOSE TO
THE TASTE RECEPTORS AND THE
NEURONS THAT ARE BLUE ARE
FURTHER AWAY.
AND NEURONS CLUSTER VERY NICELY
IN THIS SPACE, BUT IF YOU GO
FORWARD, YOU WILL SEE THAT IF WE
LOOK THEA DIFFERENT SENSORY
RECEPTOR POOLS, THERE'S LOTS OF
OVERLAP.
SO IT DOESN'T AS IF NEURONS ARE
SEGREGATED, THEY'RE REALLY
HIGHLY MIXED IN THIS
MULTISENSORY MILIEU, AND THIS
PARALLELS THE IMAGING RESULTS I
TOLD YOU ABOUT BEFORE BUT IT
PRESENTS CHALLENGES TO THINK
ABOUT HOW TO INTERPRET THESE
NEURONS IN TERMS OF THEIR
SENSORY CODING AND THE
INFORMATION THEY CARRY.
OKAY, LET'S GO FORWARD.
OKAY BUT IT'S NOT A MESS AND
THERE'S A WEIGH TO FIND LOGIC
THROUGH THIS AND THAT COMES IN
CELL TYPING MUCH OUR FIRST FORAY
INTO THIS WAS A EFFORT LED BY
GREG JEFFERS AND HE DECIDED TO
TAKE THE LABELS OF THE CELLS
THAT PRODUCED BY THE HEMIBRAIN
PROJECT THAT CAME OUT OF
GENELIA, SO THEY FOUND 5000 CELL
TYPES WITHIN A SMALLER VOLUME OF
ABOUT 22,000 NEURONS AND SO GREG
MATCHED THESE NEURONS TO OUR
DATA SET USING MORPHOLOGY AND
HERE YOU CAN SEE 1 EXAMPLE OF A
NEURON FOR THE HEMIBRAIN AND
IT'S 2 PARTNERS IN THE LEFT AND
RIGHT HEMISPHERE IN FLY WIRE, SO
THERE'S MULTIINDIVIDUAL NEURONS
IN THE CELL TYPE.
AND THEN IF YOU GO FORWARD, WE
WILL SEE THAT WE CAN ACTUALLY
ASK THE QUESTION, NOW THAT WE
MATCHED THESE NEURONS HOW
SIMILAR IS THE CONNECTIVITY.
SO HERE GREG'S LAB PLOTTED THE
CONNECTIVITY SIMILARITY WITHIN
BRAINS COMPARING TO 2 HEMISPHERE
SPHERES OF FLY WIRE AND ACROSS
BRAIN COMPARING HEMITO FLY WIRE,
IT'S ALL HIGHLY SIMILAR WHICH IS
1 OF THE REASONS WE CAN -- WE
DON'T HAVE TO DO WHAT WAS DONE
FOR MIRROR IMAGIONS.
SO IN MICRONS, THE IMAGE
RESPONSES AND THEN BUILT A
CONNECTOME.
IN THE FLY WE CAN TAKE DATA FROM
1 FLY AND RELATE IT TO THE
CONNECTOME OF ANOTHER FLY SO
IT'S VERY USEFUL IN THE SYSTEM
AS LONG AS YOU KNOW THE CELL
TYPES.
BUT WHAT I HOPE CAN YOU ALSO SEE
IS THAT THERE'S LESS SIMILARITY
OF CROSS BRAIN WITHIN THE BRAIN.
SO THERE IS INDIVIDUAL
VARIABILITY AND WE WILL HAVE TO
CONTEND WITH THAT GOING FORWARD
AS WE THINK ABOUT REALLY HOW TO
INTERPRET THESE CONNECTOMES.
SO THE OTHER WHY TO DO CELL
TYPES IS NOT BY MORPHOLOGY
MATCHING BUT CONTRADICTLY BY
CONNECTIVITY AND YOU CAN MAYBE
CLICK FORWARD, TWICE LI CHEN.
SO THE EYE CONTAINS THESE
REPEATING COLUMNS, AND THERE'S
REPEATING CONNECTIVITY, ALL
BEHIND THE FACETS OF THE EYE,
THE 800, AND THIS ALLOWS US TO
BREAK DOWN THE 43,000 NEURONS
AND 1 OPTIC LOBE INTO JUST 2030
TYPES.
AND SO CAN YOU SEE 2 EXAMPLES
HERE, THERE'S ABOUT 800 OF THESE
TM1 NEURONS BUT THERE'S FAR
FEWER OF THE DM3 NEURONS BECAUSE
THEY'RE TANGENTIAL AND THEY GO
ACROSS COLUMNS, SO THIS CELL
TYPES WAS DONE ONLY BY
CONNECTIVITY, NOT USING ANY
TRANSCRIPTIONAL INFORMATION, NO
MORPHOLOGY, O THIS IS ALSO A
PATH FORWARD FOR NEW DATA SETS
USING THE KIND OF TOOLS WE
DEVELOPED HERE FOR CELL TYPES.
YOU CAN GO FORWARD.
AND THEN, THE LAST THING I
WANTED TO MENTION IN THE REALM
OF CELL TYPING IS THAT MY LAB
ALSO LED AN EFFORT TO TAKE LIGHT
MICROSCOPIC IMAGES OF NEURONS WE
KNEW WERE SEXUALLY DISCIPLINARY
MORPHIC, IN FRUITLESS AND DOUBLE
SECTIONAL ANALYSISS, THESE WERE
LIKE THE ANDROGEN RECEPTOR OR
ESTROGEN RECEPTOR IN MAMMALS AND
HERE WE'RE FINDING THE NEURONS
IN THE EM DATA SET THAT MATCH
THIS MORPHOLOGY.
BUT WHAT'S NICE BECAUSE WE HAVE
THE EXHAUSTIVE CELL TYPING
TECHNOLOGY CAN IS WE CAN SPLIT
THEM FURTHER AND MOW WE MAKE
THIS NETWORK OF 1400 NEURONS WE
KNOW, OR WE THINK THEY DO BASED
ON MATCHING AND IN THE PLOT AT
THE LOWER LEFT, YOU CAN SEE WHAT
THE FRACTION OF INPUT AND OUTPUT
SYNAPSES IN WITHIN THIS NETWORK,
THAT'S THAT 1 BLACK DOT AND IT'S
ABOUT 12%.
SO THIS IS NOT A PRIVATE NETWORK
OVER 80% OF THE SYNAPSES COME
FROM NEURONS THAT ARE NOT
EXPRESSING FRUITLESS OR DOUBLE
SEX, BUT IT'S HIGHLY
INTERCONNECTED SO IF YOU COMPARE
TO MASH NETWORKS THAT HAVE THE
SAME SPATIAL DISTRIBUTION BUT
DON'T EXPRESS THESE
TRANSCRIPTION FACTORS THE
INPUT-OUTPUT PERCENTAGES ARE
MUCH, MUCH LOWER.
SO THIS IS A VERY INTERESTING
SET OF NEURONS.
WE KNOW THEY MUST HAVE
FUNCTIONAL REALLY VANCE TO THE
SOCIAL BEHAVIOR I TOLD YOU
ABOUT, MALE, FEMALE, SOCIAL
INTERACTIONS, BUT THEY'RE IN
THIS PUBLIC NETWORK AND WE NOW
FOR THE FIRST TIME HAVE ACCESS
TO ALL OF THEIR CONNECTIONS TO
START TO USE THIS INFORMATION TO
INFORM BEHAVIORIAL STUDIES.
OKAY, WE CAN KEEP GOING.
>> OKAY, SO, I DON'T KNOW HOW
MUCH TIME I HAVE, LIKE I SAID
JUST CUT ME OFF WHEN YOU WANT
BUT I THOUGHT I WOULD GIVE YOU
AN EXAMPLE FROM OUR OWN WORK OF
HOW WE'RE ACTUALLY GOING TO GET
FROM CELL TYPES TO BEHAVIOR, AND
I THOUGHT THE EXAMPLE I WOULD
USE ARE THE VISUAL PROJECTION
RODS.
THERE'S A COUPLE INNOVATIONS
HERE SO THE VISUAL PROJECTION
ROTS ARE BETWEEN THE OPTIC LOBE
AND THE CENTRAL BRAIN AND THE
NUMEROUS CELL TYPE HERE ARE THE
NEURONS SEEN HERE, AND THEY'VE
BEEN STUDIED FOR MANY YEARS BY A
NUMBER OF DIFFERENT GROUPS BUT
NOW IN THE FLY CONNECTOME WE
KNOW WHAT THE COMPLETE CELL TYPE
IS AND IT'S PEAP, SO THERE'S
5000 OF THESE NEURONS THAT BE
BROKEN DOWN INTO 59 TYPES AND
EACH OF THESE TYPES TILES SOME
REGION OF THE VISUAL FIELD, OF
THE LOBULA, AND PROJECTS TO A
DISTINCT GLOMERULEUS AS CAN YOU
SEE HERE.
SO IF WE GO FORWARD, THIS
ARCHITECTURE IS NICE, IT ALLOWS
US TO ASK THE QUESTION, WHAT ARE
THE FUNCTIONS OF THESE CELL
TYPES AND SO, HOW DO YOU FIGURE,
IF YOU HAVE A CELL TYPE IN THE
CONNECTOME, HOW DO YOU FIGURE
OUT FUNCTION.
OKAY, SO THERE'S ACTUALLY MANY
NICE EXAMPLES NOW, I'M GOING TO
GIVE YOU 1 FROM SEBASTIAN'S
PAPER BUT I CAN POINT TO OTHERS
IF YOU'RE INTERESTED?
SO HERE SEBASTIAN LOOKS AT THE
DM3 CELLS IN THE OPERATING
GLOBALLYIC LOBE AND THEY COME IN
3 TYPES, P, Q, V, AND IF YOU
LOOK AT THEM, CAN YOU SEE THAT
THE DENDRITES ARE POINT INDEED 3
DIFFERENT DIRECTIONS, WHAT WE
CALL THE P-AXIS AND THE Q-AXIS
IS VERTICALAXIS AND SO IT LOADS
TO THE OBVIOUS HYPOTHESIS THAT
WHAT THESE DM3 CELLS DO IS THEY
DETECT 3 DIFFERENT BARS OF
DIFFERENT ORIENTATIONS, SEEM
VERY REASONABLE SO SEBASTIAN
COULD FOLLOW THE WIRES ALL THE
WAY DOWN TO THE LC NEURON CALLED
LC 15 AND HE COULD PREDICT THAT
LC 15 DETECTS BARS BUT OF ANY
ORIENTATION BECAUSE IT COMBINES
THEMSELVES AND IN FACT,
PHYSIOLOGY HAS BORN THAT OUT SO
THAT'S AN EXAMPLE OF JUST USING
CONNECTIVITY TO MAKE PREDICTIONS
ABOUT FUNCTION.
NOW THE OTHER OPTION IS
SIMULATION, TAKING THE CONNECT
OHM AND STARTING TO SIMULATE IT
TO PERFORM FUNCTIONS AND THEN
SEEING WHAT THE NEURONS DO.
SO THERE'S BEEN A HANDFUL OF
EXAMPLES, THERE WAS A NICE PAPER
FROM KRISTIN SCOTT AND 1 FROM
TURAGA, I ENCOURAGE TO YOU LOOK
THEA THOSE EMPLOY I WILL TELL
YOU ABOUT OUR APPROACH WHICH IS
SLIGHTLY DIFFERENT.
WE CALL IT KNOCK OUT TRAINING
AND IT'S A WAY TO PERFORM
SIMULATION TO ACTUALLY DISCOVER
THE FUNCTION OF CELL TYPES SO
MAWB I WILL JUST WALK YOU
THROUGH THAT IF YOU UNDULLING
ME.
SO WHAT WE WILL DO IS WE WILL
PREDICT THE MALES BEHAVIOR, SIS
SINGING AND CHASING USING ONLY
VISUAL INFORMATION FROM THE
FETAL COMPARTMENT --
FEMALE.
SO THAT'S WHAT THE NETWORK WILL
DO.
KEEP GOING.
YES, OKAY, SO WHAT WE STARTED
WITH IS KNEE KNEW THERE WERE
GENETIC DRIVER LINES SHOWN HERE
THAT LABELED A LANDFUL OF THESE
LC TYPES AND SO YOU COULD SEE
EACH IMAGE HERE COMES FROM A
DIFFERENT GENETIC DRIVER LINE
LABELING DIFFERENT TYPE OF LC
AND THIS WAS PUBLISHED SOMETIME
AGO BY THE RISER CARD IN RUBEN
LABS, AND SO OVERTIME PEOPLE
USED THESE TO STUDY FUNCTIONS SO
THEY WOULD ACTIVATE THEM OR
SILENCE THEM.
HERE YOU SEE 1 EXAMPLE ASCRIBING
TO LC10, THE FUNCTION OF
ENCODING FEMALE ORIENTATION TO
DRIVE, AND ANOTHER EXAMPLE IS
LCLP2 THAT CODES THE SIZE OF A
LOOMING VISUAL OBLIGATIONS YECT
LIKE A PREDATOR ON THE RETINAL
-- RETINA
AND LEADS TO TAKE OFF.
SO THIS TYPE OF CELL TYPE CODE
THAT EACH OF THESE LCs ENCODES
A PARTICULAR VISUAL FEATURE AND
DRIVES A PARTICULAR BEHAVIOR.
AND I THINK STUDYING THESE LCs
1 AT A TIME, ALL OF THIS DATA
WAS VERY CONSIST WENT THAT
HYPOTHESIS EMPLOY BUT WE
WONDERED IF THERE COULD BE A
MORE DISTRIBUTED CODE HERE, IF
THESE LCs GIVEN THEIR POSITION
IN THE VISUAL SYSTEM IS THE
BOTTLENECK BETWEEN THE EYE AND
THE BRAIN ACTUALLY ENCODED
INFORMATION AS A POPULATION.
SO IN THAT HYPOTHESIS, MOST OF
THESE WOULD PROCESS INFORMATION
ABOUT THE FEMALE AND WOULD DRIVE
BEHAVIOR.
OKAY, SO HOW DO WE TEST THAT?
SO, YOU KEEP GOING.
ALL RIGHT, SO WE BASICALLY
DESIGNED A DEEP NEURAL NETWORK,
THIS IS A FEED FORWARD NETWORK
AT THE MOMENT DOESN'T HAVE ANY
INFORMATION FROM THE CONNECT
O--METABOLIZED BUT IT HAS A
BOTTLENECK LAYER WHERE WE LABEL
IN THOSE TYPES AND THE YOB CORPS
IS TO TAKE THE VISUAL INPUT THE
MALE SEE ANDS IF YOU PREDICT HIS
-- OH, SORRY, YES AT THE
BOTTLENECK LAYER, THERE'S MAYBE
SOMETHING ELSE, OH YES, WE WILL
BASICALLY PREDICT THIS AT THE
BOTTLENECK BEHAVIOR, SO WE WILL
KEEP GOING.
SO THE INPUT IS MOVIES OF WHAT
THE MALE SEES AND FOR THIS WE
USED POST TRACKING METHOD MY LAB
DEVELOPED CALLED SLEEP.
IT WAS DEVELOPED BY CARERRA, AND
HE'S STILL IMPROVING IT AND
DEVELOPING THE METHODS BUILT ON
IT.
AND SO HERE THE POST TRACKING IS
CAPTURING FOR US THE FEMALE
NOTION RELATIVE TO THE MALE AND
YOU CAN SEE THE MOVIE ABOVE IS
SORT OF THE FEMALE FROM THE
MALE'S PERSPECTIVE.
APOLOGIES IF IT DOESN'T LOOK
LIKE THAT BUT THIS IS JUST A
RENDITION.
SO LET ME TELL YOU ABOUT THE
SILENCING, IN BLACK HERE IS A
CONTROL EXPERIMENT WHERE THE
MALE IS OF THE CONTROL GENOTYPE
AND YOU CAN SEE INITIALLY HE'S
FAR FROM THE FEMALE AND THEN
OVER TIME HE GETS CLOSER AND
THEN HERE'S TO EXAMPLES OF
SILENCING DIFFERENT LC NEURONS.
SO IF YOU SILENCE LC 10 A, CAN
YOU SEE THE MALE KIND OF NEVER
GETS CLOSE TO THE FEMALE, HE
STAYS FAR, AND IF YOU SILENCE
LC22, HE'S A SUPER COURTER, HE
PURSUES THE FEMALE RIGHT AWAY
AND STAYS CLOSE TO HER.
IF AND YOU LOOK ACROSS THE
SILENCING EXPERIMENTS AND WE DID
HUNDREDS OF THESE, CAN YOU SEE
THAT THE FEMALE CONITRATION IN
FRONT OF THE MALE VARIES ACROSS
THESE DIFFERENT SILENCING
EXPERIMENTS SO FOR LC10 A, SHE'S
SORT OF DIFFUSE, HE SPENTS VERY
LITTLE TIME WITH HER, AND FOR
LPLC, 2, HE REALLY FOCUSES ON
HER AND THEN IF YOU LOOK AT
SINGING WHAT YOU WILL SEE IS
THAT HE HAS THESE 2 TYPES OF
SONG HE CAN SING, 1 OF THEM IS A
SILENT SONG, SO LC10 A SPENDS
LESS TIME CLOSE TO THE FEMALE SO
THOSE GUYS SING LESS SONG, AND
LPLC2 MALES SPEND MORE TIME
CLOSE TO THE FEMALE AND THEY
SING MORE SONG, AND I WANTED TO
TELL YOU ABOUT THAT SLID THERE'S
A CONTINUUM OF PHENOTYPES.
I CAN JUST USE WORDS, THERE'S A
CONTINUUM OF PHENOTYPES, AND I
THINK THIS IS PRETTY COMMON FOR
YOU KNOW OPTICAL IMAGES O
GENETIC OR ANY KIND OF CAUSAL
MANIPULATION EXPERIMENT, YOU
WILL GET A GRADATION OF
PHENOTYPES AND YOU HAVE TO
FIGURE OUT WHAT TO DO WITH THIS
DATA.
OFTEN WE JUST FOCUS ON THE
BIGGEST PHENOTYPE AND MOVE
FORWARD.
BUT THERE'S SOMETHING QUITE
INTERESTING HERE THAT THERE'S
SUBTLE EFFECTS WITH A LOT OF
THESE LCs SO A WAY TO STUDY
THESE IN CONCERT IF YOU GO
FORWARD, NOW IS TO ACTUALLY
CREATE A MODEL.
SO IN THE MODEL, WE TAKE THAT
DEEP NEURAL NETWORK MODEL AND WE
SET 1 CHANNEL IN THE LC LAYER TO
0, WHEN WE'RE TRAINING THE
NETWORK ON BEHAVIORIAL DATA FROM
A MALE IN WHICH THAT LC WAS
SILENCED.
AND THEN IF YOU GO FORWARD, WE
WILL SET A DIFFERENT CHANNEL TO
0 WHEN WE TRAIN WITH DATA IN
WHICH A DIFFERENT LC TYPE WAS
SILENCED AND THEN IF YOU GO
FORWARD AGAIN, CAN YOU SEE --
SORRY THAT WAS IT BUT THE POINT
WAS THAT -- THAT'S FINE -- WE
BASICALLY TRAIN UP THE NETWORK
THAT THIS WAY, SO WE'RE
BASICALLY SILENCING 1 NOTE IN
THE DNN WHEN WE'RE TRAINING ON
THIS BEHAVIORIAL DAT A. OKAY, SO
WE TRAIN UP THE WHOLE NETWORK,
WE HAVE A LAYER TRAINED SOLELY
ON BEHAVIORIAL DATA AND THEN WE
CAN ASK DOES THIS TRAIN NETWORK
DO A GOOD JOB OF PREDICTING HELD
OUT BEHAVIORIAL DATA AND IN FACT
IT DOES.
WE CALL IT TO 1 TO 1 NETWORK
BECAUSE THERE'S A 1 TO 1 MAPPING
OF LC NEURONS IN A MALE FLY AND
LC NEURONS IN THE NETWORK.
AND I JUST WANT TO TELL YOU
THERE THIS IS A BIT DIFFERENT
FROM OTHER NEURAL NETWORK MODELS
OF BEHAVIOR IN WHICH YOU MIGHT
SEE MAPPINGS BETWEEN NEURONS AND
LAYER OF THE NETWORK, HERE WE'RE
ACTUALLY MAPPING INDIVIDUAL
NOs OF NETWORK 2 INDIVIDUAL
NEURONS IN THE BRAIN.
SO IT DOES A GOOD JOB OF
PREDICTING BEHAVIOR, BUT WHAT'S
SURPRISING TO US, IF WE WENT TO
IMAGE IN THE MALES BRAIN, AND WE
RECORD FRIDAY LC NEURONS IN HIS
BRAIN, AND WE LOOKED AT THOSE
RESPONSES AND THEN WE COMPARED
THEM TO THE RESPONSES OF THE
NETWORK, SO THE NETWORK GOT THE
SAME MOVIE OF THE FEMALE AS THE
ACTUAL MALE DID AND WE ASKED
WHAT DOES THE ACTIVITY OF THE
NETWORK LOOK LIKE RELATIVE TO
HIS BRAIN.
AND IF YOU GO FORWARD, WHAT YOU
WILL SEE, IS WE FOUND THESE VERY
ASTOUNDING MATCHES, SO HERE JUST
EXAMPLES OF DIFFERENT LCs WE
RECORDED FROM AND THE NETWORK
RESPONSES.
SO THE MODEL NEVER SAW ANY
NEURAL DATA IT JUST WAS TRAINED
ON BEHAVIOR, BEHAVIORIAL
SILENCING DATA AND YET IT LEARNS
A NEURAL REPRESENTATION THAT
SEEMS TO MATCH THE ACTUAL DATA.
NOW THE PERFOR THE PURPOSANCE
ACROSS -- PERFORMANCE ACROSS AL
THE LCs IS MUCH BETTER THAN AN
UNTRAINED NETWORK BUT WE STILL
HAVE A WAYS TO GO AND I THINK
THAT WILL COME FROM PUTTING IN
THE REAL CONNECTIVITY FROM THE
CONNECTOME.
SO THIS IS ENCOURAGING FIELD
FUNCTIONS THINK WE CAN MAKE MORE
IMPROVEMENTS BY ADDING REAL
CONNECTIVITY.
ALL RIGHT, LET'S KEEP GOING.
SO OKAY, NOW WE GET TO INTERPRET
THE NETWORK AND THE FIRST THING
WE CAN ASK IS HOW DOES THIS LC
POPULATION REPRESENT THE FEMALE?
SO IF YOU GO FORWARD, YOU WILL
SEE, YEAH, THAT'S GOOD, WE CAN
MAKE MAPS OF VISUAL TUNING.
SO HERE WE BASICALLY PRESENTING
THE NETWORK WITH'S FEMALE OBJECT
THAT CAN CHANGE ORIENTATION, CAN
CHANGE SIZE OR IT CAN CHANGE
APPROXIMATION AND CAN YOU SEE
THE CELL TYPE LC10 A, PREFERS
FEMALES FACING AWAY THAT ARE
LARGE IN SIZE AND THAT ARE AT
THE CENTER OF THE VISUAL FIELD
AND THAT'S IN FACT WHAT WE KNOW
ABOUT THE CELL TYPE FROM A LOT
OF OTHER BEHAVIORIAL PHYSIOLOGY
WORK.
SO THAT IS GREAT.
OUR MODEL LEARNED REPRESENTATION
THAT MATCHES WHAT WE KNOW ABOUT
THE CELL TYPE.
BUT NOW IF YOU GO FORWARD, WE
ACTUALLY HAVE MAPS FOR EVERY
OTHER LC THAT WE MODELED AND
THERE'S A REAL BEAUTIFUL
DIVERSITY HERE, SO FOR EXAMPLE,
THE LPLC 2 NEURON I TOLD YOU
ABOUT THAT HAD ONLY BEEN -- CAN
YOU GO FORWARD -- HAD ONLY BEEN
IMPLICATED IN ESCAPE RESPONSES
WE SEE ACTUALLY IT DOES CARE
ABOUT FEMALE MOTION, BUT IN THE
PERIPHERY, THE VISUAL FIELD, SO
NOT IN THE CENTER BUT AT THE
EDGES.
THIS MIGHT EXPLAIN WHY TURNING
IT OFF MAKES MALES BETTER AT
PURSUING THE FEMALE, THIS LC31
ALSO PREFERS FEMALE IN THE
CENTER BUT ACROSS RANGES OF
SIZES AND I WILL IT YOU WHY
THAT'S IMPORTANT IN A MINUTE AND
THE LAST TYPE LC2, PREFERS
FEMALES IN THE CENTER BUT ONLY
WHEN THEY'RE FAR AWAY, SO THIS
GIVES AN IDEA OF HOW THEY MIGHT
WORK TOGETHER TO REPRESENT THE
RANGE OF DIFFERENCES THAT THE
MALE CARES ABOUT TO PRODUCE
THESE DIFFERENT BEHAVIORS.
AND I WANT TO POINT YOU TO
REALLY BEAUTIFUL PAPERS ALSO
STUDYING VISUAL TUNING IN THESE
LCs, LET'S GO FORWARD.
OKAY, SO NOW WE CAN DO A VERY
COOL EXPERIMENT WITH THE MODEL
THAT YOU JUST CANNOT DO WITH
DROSOPHILA GENETICS EVEN THOUGH,
YOU KNOW LI CHEN AND I WILL TELL
YOU CAN DO ALMOST ANYTHING WITH
DROSOPHILA GENETICS AND THAT IS
TO SILENCE OR ACTIVATE ANY
ARBITRARY NUMBER OF CELL TYPES.
ABOUT YOU HERE IN THE MODEL
BECAUSE WE MAPPED THESE NEURONS
INTO NODES IN THE MODEL, WE CAN
TURN OFF OR TURN ON ANY
ARBITRARY COMBINATION EMPLOY SO
HERE I'M SHOWING YOU HOW MANY
LCs WE WOULD HAVE TO SILENCE
TO GET NO CHANGE IN THE MALES
BEHAVIOR, IN THE MODEL AND HERE
I'M SHOWING YOU WHICH LCs WE
VALID TO TURN OFF TO COMPLETELY
BLOCK A PARTICULAR MALE
BEHAVIOR, SO THIS BASICALLY,
THESE KINDS OF EXPERIMENTS CAN
ESTABLISH FOR US THE SET OF LC
CELL TYPES THAT ARE NECESSARY
AND SUFFICIENT FOR BEHAVIOR.
SO IF YOU GO FORWARD, WHAT YOU
WILL SEE IS THAT THERE'S A VERY
RICH COMBINATORIAL CODE.
EACH LC TYPE, DRIVES A NUMBER OF
THE MALE COURTSHIP BEHAVIORS,
CHASING AND SINGING, AND EACH
BEHAVIOR IS DRIVEN BY MULTIPLE
LC TYPES.
SO THIS IS REALLY EXCITING
RESULT FOR US AND I WANT TO
UNPACK IT FOR YOU, SO THIS IS
GOING TO GET PRETTY CHALLENGING,
THERE'S A LOT OF ANIMATIONS ON
THE NEXT SLIDE THAT I'M SURE WE
WILL GET THROUGH IT.
KEEP GOING.
SO LET'S LOOK AT THIS CELL TYPE
LC31, SO GO FORWARD ONCE MORE.
WHAT WE SEE IS THAT LC31 IN THE
MODEL, DRIVES SONG AND IT DRIVES
WHEN STRONGLY ACTIVATED IT
DRIVES P-SLOW AND SIGN AND WHEN
WEEKLY ACTIVATED IT DRIVES FAST.
SO I DIDN'T TELL YOU ABOUT 2
TYPES OF SONG PULSES, 1 PRODUCED
FURTHER AWAY FROM FEMALES, 1
PRODUCED CLOSER.
LET'S GO FORWARD.
AND I TOLD THAT YOU MALES SING
DIFFERENT TYPES OF SONG, 1 NEAR
AND FAR, AND IN THE COMPLEX
SONG, HE SINGS SLOW PULSES AND
SIGN, AND THE SIMPLE SONG HE
SIGNS FAST PULSES.
ONCE MORE, AND SO WE RECENTLY
PUBLISHED A CIRCUIT MECHANISM
FOR THIS IN WHICH WE IMPLICATED
A CELL TYPE CALLED PC 2 AND
DRIVING THIS BEHAVIOR, WHEN PC 2
IS WEEKLY ACTIVATED YOU GET
AICISMEM SONG WITH FAST PULSES
AND WHEN PC 2 IS STRONGLY
ACTIVATED VIA THIS VERY NICE
DISINHIBITION MECHANISM, CAN YOU
DISINHIBIT THE SONG CIRCUITRY TO
DRIVE COMPLEX SINGING WHERE YOU
ALTERNATE BETWEEN THE SLOW
PULSES AND THE SIMPLE SONG.
SO WHAT WE SEE IN THE
CONNECTOME, I WILL BRING IT BACK
TO THE CONNECTOME.
IS THAT THE LC31 NEURON IS
DIRECTLY PRESYNAPTIC TO PC 2.
NOW THIS IS A FEMALE CONNECT
OHM, I'VE BEEN TELLING BUT MALE
BEHAVIOR, BUT IT'S VERY
INTRIGUING THAT THIS VISUAL CELL
TYPE THAT OUR MODEL FOUND TO
DRIVE SINGING IN THIS VERY
PARTICULAR WAY IS PRESYNAPTIC TO
A DIFFERENT SET OF STUDIES WE
FOUND IS IMPLICATE INDEED THE
CELL BEHAVIOR, SO THIS IS
ENCOURAGING RESULT FROM THE
CONNECTOME ABOUT THESE PIECES
BEING FIT TOGETHER.
SO NOW I THINK WE HAVE THE JOB
OF FIGURING OUT HOW ALL OF THESE
LC-TYPES ARE WORKING TOGETHER
VIA CONNECTIVITY TO DRIVE THISY
ABOUT HAD A FEW AND SO IF YOU GO
FORWARD AGAIN, I'LL JUST MENTION
TO YOU THAT LC31 HAPPENS TO BE 1
OF THE VISUAL PROJECTION NEURONS
HA IS FRUITLESS POSITIVE, THAT
IS IT EXPRESSES THAT
DISCIPLINARY MORPHIC FACTOR AND
HERE ARE 3 OTHER LC TYPES THAT
ARE ALSO FRUITLESS POSITIVE.
AND IF YOU GO FORWARD, WHAT WE
FIND IS THAT THESE NEURONS ARE
NOT PRIVATE, IN FACT, THEY ARE
IN A NETWORK IN WHICH THESE ARE
DEEPLY EMBEDDED TOGETHER AND IT
EXPLAINS TO US HOW IT IS THAT
THERE'S THE SHARED ROLES FOR
LCs IN DRIVING BEHAVIOR BUT
THESE NODES ARURE NODES ARE DRD
THAT'S THE THE HYPOTHESIS GOING
FORWARD.
GO FORWARD AGAIN, HERE YOU SEE
THE FEMALE CONNECTOME, BUT HERE
I PLOTTED THE LC'S WE STUDIED
WITH THE OPTICS IN THE LOBE, AND
ALL THE OPTIONS WE STUDIED DOWN
STREAM IN THE CENTRAL BRAIN, SO
THIS IS THE CONNECTIVITY WE'RE
CURRENTLY LAYERING INTO THE DEEP
NEURAL NELT WORK TO IMPROVE OUR
PREDICTIONS OF BEHAVIOR AND PUT
NOTHING THE REAL CONNECTIVITY
HELPS US TO GET CLOSER TO THE
REAL FLY BRAIN TO REALLY
UNDERSTAND HOW THIS KIND OF
POPULATION CODE AMONG THE LCs
CAN COORDINATE BE BEHAVIOR.
HOW IS IT THAT IT ENCODES
BEHAVIORS?
AND HOW IS IT THAT IT DRIVES
BEHAVIOR?
THAT'S WHAT WE'RE DOING NOW AND
I THINK THIS MAY BE MY LAST
SLIDE.
I THINK THE CHALLENGE FOR OUR
FIELD NOW THAT WE HAVE THESE
RICH DATA SET SYSTEM TO PREDICT
FUNCTION FROM THE CONNECT OHM SO
I TOLD BUT HOW WE'RE PREDICTING
NATURAL BEHAVIOR USING THIS
KNOCK OUT MECHANISM THEY THINK
MIGHT BE USEFUL TO A MEMBER OF
PEOPLE WE ALSO OBVIOUSLY COLLECT
VERY RICH NEURAL DATA, HERE'S AN
EXAMPLE OF A MALE FLY CHASING A
FEMALE, HE'S HEAD FIXED, RUNNING
ON A SPHREERICAL TREADMILL AND
WE'RE SIMULTANEOUSLY IMAGING HIS
BRAIN AND HERE WE EXPRESSED THE
CALCIUM SENSOR IN EVERY NEURON
AND WHAT I HOPE YOU CAN
APPRECIATE IS THAT THERE ARE
THESE BRAIN WIDE PATTERN THAT
ARE HAPPENING AS HE INTERACTING
WITH THE FEMALE.
THIS IS WHAT WE WANT TO EXPLAIN.
HOW DOES THIS RICH ACTIVITY
ARISE AND HOW IS IT BEING USED
TO DRIVE BEHAVIOR AND SO WE'RE
SORT OF GETTING THERE BY USING
THE CELL TYPES OF THE CONNECTOME
TO SORT OF GETITOUS THIS EVENT
GOAL AND I THINK WITH THAT --
OH, THE LAST THING I WANTED TO
SAY, I GUESS I HAVE 2 MORE
SLIDES.
I THINK OUR WORK NICELY FORMS A
FOUNDATION FOR THE CURRENT
FUNDING FURB WITHIN THE BRAIN
INITIATIVE CALLED BRAIN CONNECTS
AND TO GENERATE CONNECTOMES FOR
LARGER BRAINS LIKE MOUSE, AND
PRIMATE AND YOU KNOW OUR HOPE IS
THAT ALL THE GROUND WORK WE LAY
IN THE FLY, NOT JUST THE METHODS
BUT HOW WE DO CONNECTOMICS FOR
WORK AND OTHER PROJECTS
SEBASTIAN HAS TAKEN THOSE
INNOVATIONS AND APPLIED THEM
DIRECTLY BUT I ALSO SORT OF
MEANT THE FRAMEWORK, THE PATH
FOR FIGURING OUT FUNCTION FROM
THE CONNECTOME OUR HOPE IS THAT
THE WORK WE DO WILL DIRECTLY
INFORM THE STUDY BECAUSE IT'S
GOING TO GET MUCH MORE
COMPLICATED AS BRAINS GET BIGGER
AND I THINK MY LAST SLIDE IS A
THANK YOU TO MY LAB, ALSO THE
BRAIN INITTATIVE, SO EVERYTHING
I TOLD YOU ABOUT TODAY WAS
FUNDED THROUGH THE BRAIN
INITIATIVE AND IT'S AN EXAMPLE
OF RISK TAKING IN THESE PROJECTS
WERE ALL KIND OF CRAZY FROM THE
START BUT THAT I HAVE PAID OFF
IN INTERESTING WAYS SO THANK
YOU.
AND HAVE THIS PICTURE IN THE
LOWER RIGHT HAND CORNER, YAWN
AND HIS TEAM PAID US A VISIT AT
PRINCETON TO LOOK AT SOME OF THE
PROGRESS FROM THE BRAIN
INITIATIVE AND WE WERE JOINED BY
OUR LOCAL REPRESENTATIVE IN NEW
JERSEY BONNIE WATSON COLEMAN AND
IT WAS SORT OF A NICE WAY TO
SHOWCASE THE BRAIN INITIATIVE
WORK WHICH WAS, YEAH, REALLY
GREAT.
SO THANKS TO ALL OF YOU AND I'M
HAPPY TO TAKE QUESTIONS IF THERE
IS TIME AND THANK YOU SO MUCH LI
CHEN, FOR MAKING MY TALK
POSSIBLE.
>> THANKS MALA.
THAT WAS FABULOUS AS ALSO AND
THANKS LI CHEN FOR HELPING OUT.
REALLY APPRECIATE THAT.
IT'S GOOD TO BE AMONG FRIENDS
HERE SO LET'S TAKE QUESTIONS IF
FOLKS HAVE THEM.
I HAVE A BUNCH BUT I DON'T WANT
TO DOMINATE.
>> LI, YOU'RE MUTED?
>> YOU MENTIONED ABOUT PROTEIN
CONNECTOME INTO THE NETWORK.
FIRST OF ALL GREAT INTERPLAY
BETWEEN BIOLOGICAL AND NETWORK
AND ARTIFICIAL NETWORK SO YOU
MENTIONED INTO THE ARTIFICIAL
NETWORK TO HELP HIM PROVE, DO
YOU PUT SPECIFIC CONNECKS OR ARE
ALSO ADD WEIGHTS, SPECIFIC
WEIGHTS?
>> GREAT QUESTION.
SO THE WEIGHTS IN THE DROSOPHILA
CONNECTOME COME FROM THE NUMBER
OF CONNECTIONS.
I MENTIONED THAT WHEN 2 NEURONS
CONNECTS THEY OFTEN DO SO OVER
MULTIPLE TIN APSES AND SO WE USE
THE NUMBER OF SYNAPSES AS THE
WEIGHT.
AND THAT'S ACTUALLY WORKED OUT
WELL SO THERE'S A VERY NICE
PAPER FROM A COLLEAGUE WHO USED
THE CONNECTION OF WEIGHTS AND
GOT GOOD RESULTS.
SO I THINK AS PEOPLE ARE
SIMULATING THE CONNECTOME, THIS
PROXY FOR WEIGHT SEEMS TO WORK
WELL, BUT IT'S NOT GOING TO WORK
IN ALL CASES AND I THINK IT WILL
BE INTERESTING TO FIGURE OUT
WHERE IT FAILS AND WHAT OTHER
INFORMATION WE HAVE TO ADD.
SO WE USUALLY DON'T TRIM THE
WEIGHT, WE USE THE NUMBER OF
SYNAPSES FROM THE CONNECTOME AS
THE WEIGHTS AND IT'S A VERY
USEFUL, I WOULD SAY COON STRAINT
IN THE MODELS BECAUSE OTHERWISE
MODEL WOULD BE WAY TO
UNCONSTRAINED.
>> THANKS.
NTED?
>> HELLO, HI, MALA, THANKS FOR A
TERRIFIC TALK, GLAD IT CAME
THROUGH.
HAD A QUESTION, MORE A
SPECULATIVE QUESTION, BUT AS YOU
YOU KNOW REALLY LOOK UNDER THE
HOOD OF THIS AND DONE TROUBLE
SHOOTING AND THOUGHT ABOUT THESE
CIRCUITS IS THERE ANYTHING YOU
CAN LEARN FROM HOW THESE MIGHT
DEVELOP FROM WHAT YOU SEE IN
YOUR DATA.
>> YEAH, NO, THAT'S A GREAT
QUESTION.
I THINK ACTUALLY HAVING
CONNECTOMES, LEADS NATURALLY TO
QUESTIONS ABOUT DEVELOPMENTAL
BIOLOGY AND ABOUT CELL BIOLOGY.
SO I THINK THERE'S THIS NICE
FEEDBACK LOOP THAT I'M VERY
EXCITED ABOUT.
ONE OF THE PROJECTS WE'RE
PLANNING TO INITIATE HERE IS 1
OF BUILDING PEOPLE DEVELOPMENT
CONNECTOME SO PICKING DIFFERENT
TIME POINTS ALONG PEOPLE
DEVELOPMENT AND THAT'S SORT OF
INTERESTING BECAUSE THE NERVOUS
SYSTEM IS RESTRUCTURING DURING
METAMORPHOSIS DURING THE FLY.
>> ESPECIALLY IN THE FLY, IT'S
CRAZY TO SEE.
>> YEAH, THERE IS A NICE
DEVELOPMENTAL TIME SERIES FOR
THE C-ELEGANS CONNECTED BY MASON
AND I YEAH, I DON'T HAVE MUCH
MORE TO SAY ABOUT THAT BECAUSE
THERE IS SO MUCH I CAN INFER
ABOUT DEVELOPMENT AFTER LOOKING
AT THE ADULT BRAIN CONNECTOME,
BUT HAVING THE CONNECTOME LEADS
NATURALLY TO QUESTIONS ABOUT
DEVELOPMENT AND I'M HOPING WE
CAN ANSWER SOME OF THOSE.
>> AND YEAH, THERE ARE STUDIES
WHERE THEY PEOPLE HAVE TRAINED
LARVAY AND SEEING HOW THAT MIGHT
WORK OUT IN CONNECT CAN ALSO
EVENTUALLY BE INTERESTING.
THANKS A LOT.
>> YEAH, SURE.
>> JIM?
>> >> THANKS MALA, REALLY
FASCINATING.
I WAS WONDERING IF YOU COULD
INPUT ANYTHING ABOUTASTROCYTE
INTERACTIONS AND DIFFERENCES IN
THE BEHAVIOR AND THOSE
INTERACTIONS.
>> YEAH, THAT'S A GREAT
QUESTION.
SO I DIDN'T TALK ABOUT TBLIA AT
ALL BUT THERE IS GLUE MARIOUSA
GLUE MARIOUS --
GLUE MARIOUSA IN THE DATA SET,
AND THERE HAVE BEEN -- SO THE
PART OF THE FLY WORK CONSORTIUM
IN OUR DISSEMINATION EFFORT HAS
BEEN TO GET NEW SCIENTISTS
INVOLVED IN DATA.
COMPUTER SCIENTISTS WHO WANT TO
DO MODELING ON THESE KINDS OF
COMPLEX GRAPHS BUT ALSO
SCIENTISTS WHO WORK ON
NONNEURONAL CELLS AND YEAH, SO
THERE'S A FEW PEOPLE WORKING ON
GLIA, I THINK THERE'S MORE WORK
TO DO SO FIRST WE HAVE TO CLEAN
UP THE GLIA AND THEN LOOK AT
PROXIMITY TO DIFFERENT CELL
TYPES.
WE DON'T HAVE A LOT OF
INFORMATION IN THE CONNECTOME
YET BUT THERE ARE A GROUPS
WORKING ON ADDING THAT
INFORMATION TRYING TO REGISTER
IT INTO IMAGES WHERE THEY STAY
FOR THESE DIFFERENT RECEPTORS SO
I THINK THERE'S EXCITING THINGS
THAT CAN COME OUT OF THIS, BUT
IT'S YOU KNOW, I ENCOURAGE
ANYBODY WHO WANTS TO WORK ON
THESE QUESTIONS TO GET INVOLVED.
YEAH.
NTHANK YOU.
NTHANKS MALA, I WAS GOING TO ASK
YOU WHAT DO WE KNOW ABOUT
MOLECULAR CORRELATES WITH THESE
ANATOMICALLY IDENTIFIED CELL
TYPES.
AND 1 REASON WE BRING IT UP IS
WHEN WE INITIALLY LOOKED AT THE
TLFR PROJECTIONS IN THE MOUSE
CORTEX THERE WAS NOT A 1 TO 1
CORRESPONDENCE BETWEEN WHAT WE
DEFINE TRANSCRIPTOMICLY AS A
CLUSTER, VERSUS THE TARGET.
AND THAT COULD BE BECAUSE YOU
KNOW THERE'S OTHER THINGS GOING
ON OR IT COULD BE SOMETHING THAT
HAPPENED THAT'S NO LONGER
PRESENT.
SO HOW FAR ARE WE GETTING WITH
THAT TO IDENTIFY IF YOU CLASSIFY
THE CELL AS X, VERSUS Y, WHAT
DID YOU FIND THE UNIQUE
MOLECULAR IDENTITIES WITH THOSE
CLASSIFICATIONS.
>> SO THERE'S BEEN QUITE A LOT
OF TRANSCRIPTIONAL WORK DONE IN
DROSOPHILA DOFFILLA, AND WE CAN
ACTUALLY AND I WOULD SAY,
PROBABLY THE BEST COMPARISON IN
THE OPTIC LOBE WHERE WE HAD
2/3RD CELL TYPES REALLY WELL
DEFINED BUT SO FAR AS I
UNDERSTAND THE NUMBER OF
TRANSCRIPTIONAL TYPE SYSTEM
LOWER.
AND THAT COULD BE FOR 1 OF 2
REASONS, 1 IS THAT WE HAVEN'T
SEQUENCED DEEPLY ENOUGH OR
THERE'S DEGENERACY WHERE YOU GET
MOWLT PEL TYPES FROM 1
TRANSCRIPTIONAL TYPE AND I THINK
THOSE IS ITS ARE ONGOING AND WE
WILL HAVE TO SEE HOW IT TURNS
OUT BUT I DO WANT TO ENCOURAGE
PEOPLE TO THINK ABOUT CONNECT
OMIC TYPES.
TO ME IT'S KIND OF THE GOLD
STANDARD.
HAVE YOU THE COMPLETE
CONNECTIVITY SO YOU CAN KNOW
EXACTLY WHETHER 2 CELLS ARE OF
THE SAME TYPE OR DIFFERENT.
AND SO FAR IT SEEMS TO BE OF
HIGHER RESOLUTION THAN JUST
TRANSCRIPTIONAL PROFILES, AT
LEAST IN THE FLY: SO I THINK
THAT'S SOMETHING THAT WILL COME
OUT OF THESE NEW DATA SETS LIKE
MICRONS IS SORT OF WHAT ARE THE
CELL TYPES, I'M EXCITED TO SEE
THE RESULTS OF THAT.
>> YEAH AND AS MENTIONED BEFORE,
WE DON'T KNOW THE DEVELOPMENTAL
HISTORY, IT COULD BE THAT YOU
KNOW THINGS WERE EXPRESSED TO
SPECIFY INTRUCTIVELY EARLY THAT
ARE NOW GONE O IT COULD BE THAT
THESE TRANSCRIPTIONAL STATE OR
PHENOTYPES OR PATTERNS OR SIMPLY
PERMISSIVE FOR MULTIPLE
DIFFERENT TYPES OF CONNECTIVITY
PATTERNS BUT IT WOULD BE REALLY
COOL TO SORT THAT OUT.
ROY?
>> MALA, THAT WAS INCREDIBLE
EMPLOY I LOVE TED'S QUESTION
ABOUT DEVELOPMENT.
I WILL GO THE DIRECTION OF
DISEASE.
I WOULD LOVE TO KNOW WHAT YOUR
THOUGHTS ARE WHEN AND HOW WE
MIGHT BE ABLE TO START USING
THESE BEAUTIFUL CONNECTOMIC MAPS
TO START TO GIVE US INSIGHT,
PREDICTIONS ABOUT DISEASE AND
MAYBE EVEN JUST DYSFUNCTION AND
SYMPTOMS RELATED TO DISEASE,
MAYBE NOT THE ACTUAL DISEASE?
>> YEAH, THANK YOU ROY FOR THE
QUESTION AND WELCOME TO THE
MCWG.
>> THANK YOU.
>> AND I THINK THIS IS GREAT AND
I ACTUALLY THINK DROSOPHILA CAN
BE OF SIGNIFICANT VALUE BECAUSE
WE KNOW THAT MANY DISORDERS ARE
CAUSE BY DEFECTS AND BRAIN
WIRING BUT WE DON'T KNOW HOW.
WHAT IS THE CONQUENCE FOR
FUNCTION THAT COMES FROM THAT
DEFECT AND WIRING, AND SO, YOU
KNOW THERE'S I THINK SORT OF 2
POSSIBLE AVENUES IN DROSOPHILA,
1 IS WE HAVE VERY LARGE
COLLECTIONS OF MUTANTS FOR
PARTICULAR GENES, ALMOST EVERY
HUMAN DISEASE GENE HAS A
HOMOLOGUE IN DROSOPHILA, AND SO
WE REQUEST START TO USE THESE
IMAGINE HAVE YOU A COMPLOAT
CONNECT OHM OF A MUTANT, NOW YOU
CAN -- NOW CAN YOU FIGURE OUT
WHERE ALL THE CHANGES AND WIRING
ARE AND HOW THEY MIGHT RELATE TO
FUNCTION.
THE OTHER THING I THINK WE CAN
DO IS ACTUALLY START TO MODEL
THE CONNECTOME SO WE CAN CREATE
ARTIFICIAL MISWIRING.
WHICH CONNECKS CAN WE GET RID OF
SORT OF LIKE I TOLD YOU WITH THE
MODELING.
HOW MANY CAN WE REMOVE AND HAVE
NO EFFECT ON THE BEHAVIOR?
HOW MANY CAN WE ADDED SO WHERE
THE PLACES IN THE NETWORK THAT
ARE SENSITIVE TO PUSH TURBATION,
AND I KNOW THE DROSOPHILA BRAIN
IS NOT ORGANIZED LIKE THE
MAMMALIAN BRAIN BUT IT SHARES A
LOT OF SAME COMPUTATIONS SO
THERE'S FUNCTIONS THAT
DROSOPHILA PERFOR THE PURPOSES
LIKE NAVIGATION, THAT WE KNOW
ARE COMPLETELY CONSERVED WITH
MAMMALIAN BRAINS, NOT ONLY AT
THE COMPUTATIONAL LEVEL BUT ALSO
IN IMPLEMENTATION, SO I THINK
THAT'S ENCOURAGING TO THINK
ABOUT USING THE BEHAVIORIAL READ
OUT AS A WAY TO PROBE THESE
QUESTIONS AND I THINK IT'S
EBSIGHTING AND I'M HOPING WE CAN
USE FLIES TO MAKE MORE PROGRESS
THERE.
>> TERRIFIC, OTHER QUESTIONS?
CAN I ASK ANOTHER 1.
SO YOU DESCRIBE BEAUTIFULLY THE
LC NEURONS IN THE MALES, THE
ACTIVITY OF COURSE USING THE
FEMALE MAP, BUT YOU HAVE THE
HEMIBRAIN TO COMPARE IT TO AND
THE HEMIBRAIN WAS FROM A MALE,
MALE FLY.
>> IT WAS A FEMALE.
>> OH WAS IT?
>> YEAH, SO IT WAS A DIFFERENT
--
>> NEVER MIND.
NEVER MIND.
>> ACTUALLY I DO THINK, SO WE'VE
ACTUALLY JUST IMAGED A MALE
BRAIN AT PRINCETON AND GENELIA
ALSO HAS A MALE BRAIN THAT
THEY'RE PLANNING TO RELEASE, AND
SO I THINK WE WILL HAVE THESE
SEX DIFFERENT DATA SETS.
BUT IN THE NERVE CORD, THE
FEMALE BRAIN AND NERVE CORD, THE
BRAIN IS A FEMALE, BUT G, NELIA
ALREADY RELEASED A MALE NERVE
CORD AND THERE WE CAN MAKE
DETAILED COMPARISONS BETWEEN THE
MALE AND FEMALE.
IT'S QUITE INTERESTING BECAUSE
IT TURNS OUT IT'S NOT TRIVIAL TO
FIGURE OUT WHICH NEURONS ARE
JUST DIFFERENT BECAUSE THESE ARE
2 DIFFERENT FLIES, AND WHICH
NEURONS ARE DIFFERENT BECAUSE
THEY'RE FROM 2 DIFFERENT SEXES
AND THAT'S KIND OF AN
INTERESTING COMPUTATIONAL
PROBLEM WE'VE BEEN WRESTLING
WITH RECENTLY.
>> GREAT, THANKS, TOR?
>> YEAH, THANKS, I THOUGHT THAT
WAS REALLY BEAUTIFUL AND THE
NEURAL NETWORK IS AMAZING THAT
YOU COULD TRAIN IT WITHOUT ANY
DIRECT TRAINING ON NEURAL
ACTIVITY THAT YOU'RE STARTING TO
PREDICT THE ACTIVITY OF THESE
DIFFERENT TYPES OF CELLS.
IF I UNDERSTAND RIGHT AND
BEHAVIOR.
I'M WONDERING IF YOU COULD
SPECULATE ON THE LIMITS OF
PREDICTABILITY, SO YOU WILL
PREDICT A LOT BUT YOU KNOW WHAT
DO YOU THINK IS IRREDUCIBLE OR
RELEASED OR STOCHASTIC AND WHAT
DO YOU PREDICT?
>> YEAH, I GUESS I SORT OF
SUGGESTED 1 DIRECTION WHICH IS
THAT WE MIGHT NEED TO PUT IN
MORE INFORMATION ABOUT THE WIRES
TO IMPROVE OUR PREDICTABILITY
BUT I THINK WHAT YOU'RE GETTINGA
THE IS THAT BEHAVIORS KIND OF
VARIABLE AND YOU KNOW WHAT'S
SORT OF THE LIMIT OF
PREDICTABILITY WITH THESE
MODELS.
I DON'T HAVE A GREAT ANSWER TO
THE QUESTION BECAUSE IT IS TRUE
THAT WE'RE, YOU KNOW WE'RE
TRAINING THE MODELS WITH THIS
LARGE DATA SET.
WE PREDICT THE DAILY BASIS THEA,
IT DOES A GOOD JOB BUT HOW WELL
DOES IT CAPTURE VARIATION, THIS
MODEL IS DETERMINISTIC IN A WAY
AND IT DOESN'T HAVE SORT OF
STOCHASTIC NOISE AND
VARIABILITY.
SO I THINK THAT'S AN INTERESTING
QUESTION AND I THINK CAN THINK
OF WAYS TO EXPLORE IT, SO I CAN
THINK OF EXPERIMENTS WHAT COULD
DO WITH MODELING TO GET AT THIS
ISSUE BUT 1 THING I WOULD SAY IS
THAT AS THESE NEW DATA SETS COME
ON LINE AND AS WEB CONNECTED
ACTUALLY START TO YOU KNOW
FIGURE OUT HOW INDIVIDUALS
DIFFER AND WHERE THEY DIFFER IN
THE CIRCUITS, I THINK WE WILL
HAVE MUCH BETTER HYPOTHESIS,
ABOUT SORT OF THE ORIGINS OF
INDIVIDUAL VARIABILITY AND WHAT
IT MEANS FOR ROBUSTNESS.
YOU KNOW SOME OF THESE
BEHAVIORS, THESE COURTSHIP
BEHAVIORS THEY'RE SO CRITICAL TO
THE LIFE OF AN ANIMAL.
YOU DON'T WANT TO MESS THEM UP.
YOU WILL NOT BE SUCCESSFUL AS A
SUITOR OR AS A MATE AND SO WHERE
DOES THAT ROBUSTNESS COME FROM
IF I THINK WE WILL HAVE BETTER
ANSWERS TO THAT SOON.
>> THANKS.
OH JOHN, YOU'RE MUTED.
SORRY.
>> SORRY.
NO IT'S REALLY COOL, I'M REALLY
EXCITED TO SEE KLF-TWO OTHER
CONNECTOMES AND I IMAGINE IF 1
IS INTERESTED IN A SPECIFIC
BEHAVIOR, 1 COULD HONE IN ON
THAT SUBREGION AND DO MORE
SAMPLES.
SO, HOW MUCH FASTER -- OKAY, THE
FIRST 1'S ALWAYS GOING TO BE THE
HARDEST TO DO BUT IN TERMS OF
THE SEGMENTATION ALGORITHMS,
WHERE ARE YOU IN TERMS OF PROOF
READING?
I MEAN IN TERMS OF SPEED AND
EFFICIENCY?
HOW MUCH FASTER IS IT?
>> YEAH, SO, YOU KNOW THE
HEMIBRAIN THAT WAS 22,000
NEURONS TOOK 50 PERSON YEARS TO
PROOF READ, THAT 50 PEOPLE
WORKING FULL IF I'M FOR A YEAR
-- FULL-TIME FOR A YEAR, OUR
PROJECT WHICH IS 140,000 NEURONS
TOOK LESS THAN 3 YEARS.
BUT THE DATA IS DEFINITE BUT THE
PROCESS HAS GOTTEN FASTER AND
THERE'S ALSO LOTS OF OTHER
PIECES OF THE PIPELINE THAT HAVE
IMPROVED THAT SPEED AT WHICH WE
CAN IMAGE, YOU KNOW THE SPEED AT
WHICH WE CAN RECONSTRUCT THESE
VOLUMES, SO THIS IS WHAT I MEANT
IS THAT IT'S SO VALUABLE TO DO
THESE SMALLER CONNECT OHMS
BECAUSE AND THIS DIDN'T GET
WASTED AND EVERY PIPELINE
INCORPORATES THE PRIOR ADVANCES
BUT YEAH, I THINK WE'RE AT A
STAGE NOW WHERE YOU KNOW IT'S
NOT A FANTASY TO THINK ABOUT ROY
ASKED THIS QUESTION, CAN YOU DO
CONNECTOMES AND MUTANTS AND
THINK ABOUT DISEASE, I DON'T
THINK UNREASONABLE TO HAVE THAT
BE PART OF THE PROJECT.
I WILL TAKE A MUTANT AND A
CONNECTOME AND LOOK AT THE
RESULTS.
SO I THINK WE'RE GETTING INTO
THE A REGION WHERE WE'RE AT
LEAST FOR DROSOPHILA, IT'S
POSSIBLE, AND 1 OF THE REASONS
IS THAT THERE'S SO MANY
AUTOMATED WAYS NOW, ONCE YOU
HAVE 1 CONNECTOME TO USE THAT
INFORMATION TO AUTOMATICALLY
PROOF READ THE NEXT 1.
>> RIGHT, RIGHT, RIGHT.
TERRIFIC, WE'RE ACTUALLY RUNNING
A FEW MINUTES AHEAD DESPITE OF
THE GLYPHS, THANKS MALA, AND
THANK YOU LIQUN, I HAVE TO SEND
HIM A BOTTLE OF WINE OR
SOMETHING, I WILL BE SENDING HIM
A PRESENT, TOO.
OKAY, SUSAN WHAT SHOULD WE --
WHAT DO YOU WANT TO DO ABOUT THE
BREAK IN.
>> WELL, WE ARE SCHEDULED TO
BREAK UNTIL 2:30.
I THINK WE SHOULD LEAVE IT AT
THAT.
WE GET 4 EXTRA MINUTES.
JUST A REMIND THEY'RE YOU WILL
HAVE TO RESIGN IN INTO THIS NEW
MICROSOFT TEAMS LINK.
SO, WE WILL SEE YOU IN ABOUT A
HALF AN HOUR.
>> THANKS EVERYBODY.
>> APPRECIATE IT.
>> BYE?
THANK YOU.