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I'M MICHA MICHAEL CHIANG, DIR

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OF THE NATIONAL EYE INSTITUTE.

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I WANT TO WELCOME YOU TO THIS

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2024 SAYER VISION RESEARCH

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LECTURE.

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SO THANKS TO EVERYBODY WHO'S

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JOINING US HERE AT THE NIH

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CLINICAL CENTER AND ALSO ON THE

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VIDEOCAST ONLINE.

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AND WE'RE REALLY GLAD THAT YOU

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COULD BE PART OF THIS VERY

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SPECIAL EVENT.

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SO FIRST OF ALL, I WANT TO GIVE

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A HUGE THANKS TO OUR SPEAKER

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WHO'S DR. MARLA FELLER, WHO'S

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FROM UNIVERSITY OF CALIFORNIA AT

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BERKELEY, AND THERE'S GOING TO

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BE A LOT MORE THAT YOU'RE GOING

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TO HEAR ABOUT DR. FELLER AND

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OBVIOUSLY FROM DR. FELLER.

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AND SHE'S REALLY GOING TO SHARE

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SOME REALLY RYE MARKABL REMARKAS

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INTO THE VISUAL SYSTEM HERE.

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IN ADDITION TO THAT, I WANT TO

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THANK OUR COLLEAGUES AT THE

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FOUNDATION FOR THE NATIONAL

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INSTITUTES OF HEALTH, THE FNIH,

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AND DR. JOE MINETSKI WHO WILL

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SAY A LITTLE BIT MORE COMING UP

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HERE.

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JOE, IT'S BEEN AWESOME TO HAVE

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YOUR SUPPORT AND COLLABORATION

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THROUGH THIS AND ALL THE OTHER

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PROJECTS WE'VE WORKED ON

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TOGETHER.

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AND SO A BIG THANKS TO OUR

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ORGANIZING TEAM FROM THE NEI,

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AND ALSO FROM THE FNIH.

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THE FOLKS IN THE BACK WHO ARE

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WORKING THE A.V. AND THE OTHER

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EVENT SUPPORT, A LOT OF PEOPLE

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WORKED REALLY HARD TO MAKE

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TODAY'S EVENT POSSIBLE.

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SO AT THIS POINT, WHAT I WANT TO

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DO IS JUST TAKE A MOMENT TO

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REFLECT ON THE LEGACY OF

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DR. JANE SAYER.

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IT WAS DR. SAYER'S VISION AND

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DEDICATION THAT BROUGHT THIS

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SERIES TO LIFE.

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IN 2006, DR. SAYER WAS A

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PIONEERING SCIENTIST AT NIDDK,

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THE NATIONAL INSTITUTES OF

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DIABETES AND DIGESTIVE AND

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KIDNEY DISEASES AND SHE WAS THE

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ONE THAT REALLY ESTABLISHED THIS

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LECTURE.

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AND IN PARTNERSHIP WITH US AT

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THE NEI AND WITH THE FNIH.

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AND SHE DID THIS REALLY TO HONOR

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HER PARENTS, WHO WERE WINTHROP

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AND LAURA SAYER AND TO CREATE A

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PLATFORM FOR CELEBRATING

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GROUNDBREAKING RESEARCH IN

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VISION SCIENCE.

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THIS LECTURE SERIES REALLY

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REFLECTS DR. SAYER'S DEEP

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COMMITMENT TO INTERDISCIPLINARY

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COLLABORATION, AND BY FOSTERING

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CONNECTIONS BETWEEN VISION

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SCIENCE AND OTHER FIELDS, IT'S

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REALLY BECOME A CORNERSTONE TO

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ADVANCING RESEARCH THAT CAN

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EVENTUALLY HAVE OBVIOUSLY FAR

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REACHING MEDICAL APPLICATIONS.

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SO THANKS TO DR. SAYER'S

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EFFORTS, WE'RE ABLE TO BE HERE

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TODAY TO CELEBRATE AND LEARN

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FROM THE WORK OF ESTEEMED

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SCIENTISTS LIKE DR. FELLER THAT

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REALLY EMBODY THE SPIRIT OF

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INNOVATION.

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SO TODAY WE'RE REALLY HONORED TO

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HAVE DR. MARLA FELLER WITH US.

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I KNOW MANY OF YOU KNOW HER FROM

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BEFORE, AND WE SEE SOME OF YOU

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COMING UP HERE AND INTRODUCING

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YOURSELVES AND LOVE SEEING THAT.

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AND MANY OF YOU KNOW AND YOU'LL

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HEAR THAT HER RESEARCH ON REALLY

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PROVIDES INSIGHTS ON THE SORTS

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OF MECHANISM THAT SHAPE HOW WE

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SEE THE WORLD.

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SO I THINK THAT DR. FELLER'S

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WORK REALLY EXEMPLIFIES THE SORT

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OF TRANSFORMATIONAL SCIENCE THAT

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THE SAYER LECTURE IS REALLY

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MEANT TO HIGHLIGHT.

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SO AT THIS POINT, WHAT I WANT TO

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COULD IS WELCOME DR. JOE

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MINITSKI, SENIOR VICE PRESIDENT

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AND CHIEF TRANSLATIONAL SCIENCE

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OFFICER, AND HE'S GOING TO GIVE

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SOME REMARKS ON THE SIGNIFICANCE

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OF THIS COLLABORATION.

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SO WITH THAT, COULD YOU PLEASE

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JOIN ME IN WELCOMING JOE TO THE

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STAGE.

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[APPLAUSE]

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>> THANKS, DR. CLANG.

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 CHIANG.

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I AM DELIGHTED TO WELCOME YOU

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HERE TO THE 2024 SAYER VISION

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LECTURE AND TODAY WE ARE PLEASED

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TO HONOR DR. MARLA FELLER WHO

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WILL PRESENT TODAY'S LECTURE AND

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I AM LOOKING FORWARD TO THAT

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PRESENTATION BECAUSE I WAS

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LOOKING OVER YOUR WORK AND IT'S

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VERY COMPLICATED.

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[LAUGHTER]

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I'M A SIMPLE BIOCHEMIST.

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IT'S VERY INTERESTING.

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AS YOU MAY KNOW, ALL OF YOU MAY

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KNOW, THE FOUNDATION FOR NIH WAS

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ESTABLISHED ABOUT 25 YEARS AGO

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BY CONGRESS TO SUPPORT THE

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MISSION OF NIH IN THREE MAIN

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WAYS.

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THE FIRST IS TO ACCELERATE THE

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GENERATION OF NEW THERAPIES AND

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NEW DIAGNOSTICS.

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THE SECOND IS TO HELP DEVELOP

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AND ADVANCE GLOBAL HEALTH.

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AND THE THIRD IS WE CELEBRATE

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GREAT SCIENCE AND GREAT

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SCIENTISTS, AND THAT'S WHY WE'RE

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HERE TODAY.

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SO AS DR. CHIANG SAID IN 2006,

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DR. SAYER ESTABLISHED THE SAYER

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VISION RESEARCH FUND, AND TO

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HONOR HER FAMILY AND

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PARTICULARLY HER PARENTS.

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THE SAYER VISION LECTURE THAT

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WE'RE HAVING TODAY IS ORGANIZED

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BY NEI AND SO WITH THE HELP OF

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FNIH, AND THE ANNUAL

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PRESENTATION FEATURES AN

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INVESTIGATOR WHO IS CONDUCTING

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OUTSTANDING RESEARCH IN THE AREA

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OF VISION AND RELATE AREAS.

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AND DR. FELLER'S WORK IS EXACTLY

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THE TYPE OF RESEARCH THAT THIS

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LECTURE AND DR. SAYER WAS MEANT

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TO RECOGNIZE AND CELEBRATE.

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WE WERE DEEPLY SADDENED TO LEARN

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OF DR. SAYER'S PASSING LAST

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DECEMBER, HOWEVER, WE ARE

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PROFOUNDLY GRATEFUL FOR HER

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SUPPORT, WHICH WILL ALLOW US TO

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CARRY ON HER VISION WITH THIS

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LECTURE TODAY.

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TRYING TO KEEP THIS SHORT, I

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WILL NOW TURN THINGS BACK OVER

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TO DR. HENDRICK NEBORG TO

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INTRODUCE DR. FELLER.

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THANK YOU FOR JOINING US FOR

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THIS EVENT AND PLEASE ENJOY THIS

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LECTURE.

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[APPLAUSE]

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>> SO WELCOME FOR THE
THIRD TIME

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FOR THIS YEAR'S DR. JANE SAYER'S

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VISION RESEARCH LECTURE.

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I'M A SENIOR INVESTIGATOR AT THE

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NEI, AND IT'S A TRUE HONOR FOR

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ME TO INTRODUCE TODAY'S SPEAKER

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AND SAYER AWARD RECIPIENT,

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PROFESSOR MARLA FELLER.

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DR. FELLER IS DISTINGUISHED

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PROFESSOR, FORMER HEAD OF THE

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DIVISION OF FLUORO BIOLOGY AND

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DEPARTMENT OF MOLECULAR AND CELL

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BIOLOGY AND A MEMBER OF THE

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HELEN WILLS NEUROSCIENCE

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INSTITUTE AT THE UNIVERSITY OF

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CALIFORNIA, BERKELEY.

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WITH A BACHELOR'S AND A PH.D. IN

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PHYSICS ALSO FROM BERKELEY

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STUDYING THE PROPERTIES OF

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LIQUID CRYSTAL INTERFACES AND

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RESEARCH STATES AS BELL LABS,

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SHE IS A PHYSICIST TURNED GIANT

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IN NEUROSCIENCE.

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THE WAY IN WHICH DR. FELLER HAS

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LEVERAGED HER INTERDISCIPLINARY

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BACKGROUND TO ADDRESS DEEP

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QUESTIONS ABOUT THE DEVELOPMENT

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OF NEURAL CIRCUITS IS TRULY

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INSPIRING.

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WHEN SWITCHING TO NEUROSCIENCE

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AS A POSTDOC, SHE USED HER

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BACKGROUND IN PHYSICS TO PIONEER

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MICROSCOPY TECHNIQUES FOR

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IMAGING IN LARGE POPULATIONS OF

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CELLS.

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SHE THEN CAPITALIZED ON THESE

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TECHNIQUES TO REVEAL THE

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DYNAMICS OF SPONTANEOUS ACTIVITY

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IN THE RETINA THAT OCCURRED

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DURING EYE DEVELOPMENT EVEN

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BEFORE BIRTH, CALLED RETINAL

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WAVES.

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THIS FOUNDATIONAL DISCOVERY HAS

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BEEN CENTRAL TO HER LAB'S

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RESEARCH SINCE.

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SHE INITIALLY STARTED HER OWN

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LAB HERE AT NIH AT THE NINDS,

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BUT AFTER A VERY SHORT PERIOD

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ACTUALLY, SHE WAS RECRUITED AWAY

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FROM THE UNIVERSITY OF

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CALIFORNIA SAN DIEGO, WHERE SHE

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RAPIDLY MOVED THROUGH THE RANKS

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BEFORE RETURNING TO HER ALMA

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MATER, UC BERKELEY, WHERE SHE

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HAS BEEN SINCE.

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SHE EXAMINES THIS AT THE LEVEL

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OF THE RETINA BY COMBINING

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QUANTITATIVE IMAGING, PHYSICIAN

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PHYSIOLOGY, GENETIC AND MORE

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RECENTLY BEHAVIORAL APPROACHES

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IN MICE.

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HER LAB IS PRIMARILY FOCUSED ON

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INVESTIGATING THE MECHANISMS

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THAT UNDERLIE RETINAL WAVES IN

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THE DEVELOPMENT OF THE NERVOUS

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SYSTEM AND THE SIGNIFICANCE OF

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THIS IN THE FORMATION OF RETINAL

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NEURONAL CIRCUITS.

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HER FINDINGS REALLY CHANGED THE

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WAY WE THINK ABOUT HOW SENSORY

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SYSTEMS DEVELOP, SHOWING THAT

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THIS EARLY NEURAL ACTIVITY CAN

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REALLY SHAPE BRAIN ARCHITECTURE

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BEFORE AN INDIVIDUAL EVEN

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EXPERIENCES ANY TYPE OF VISUAL

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INPUT.

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AN INTRIGUING RECENT EXAMPLE OF

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THIS IS HER GROUP'S WORK ON MAPS

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OF THE -- THESE MAPS SHOW SKEWS

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FOR THE REPRESENTATION OF OPTIC

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FLOW THAT IS BIASES FOR THE

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MOTION GENERATED BY AN ANIMAL'S

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MOVEMENT THROUGH SPACE.

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YET HER GROUP'S WORK FOUND THAT

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THESE BIASES ARE PRESENT EVEN

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BEFORE AN ANIMAL EVER HAD ANY

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EXPERIENCE OF OPTIC FLOW.

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00:09:04,846 --> 00:09:06,648
AND HER LAB DISCOVERED THAT THE

259
00:09:06,648 --> 00:09:10,218
DEVELOPMENT OF A PARTICULAR TYPE

260
00:09:10,218 --> 00:09:13,388
OF RETINAL GANGLION CELLS DEPEND

261
00:09:13,388 --> 00:09:19,861
ON THESE RETINAL WAVES.

262
00:09:19,861 --> 00:09:22,697
SHE LEADS A LAB WELL-FUNDED BY

263
00:09:22,697 --> 00:09:25,200
SEVERAL GRANTS.

264
00:09:25,200 --> 00:09:27,836
SHE IS A MEMBER OF THE AMERICAN

265
00:09:27,836 --> 00:09:28,537
ACADEMY OF ARTS AND SCIENCES, AS

266
00:09:28,537 --> 00:09:30,005
WELL AS THE NATIONAL ACADEMY OF

267
00:09:30,005 --> 00:09:31,239
SCIENCES.

268
00:09:31,239 --> 00:09:33,175
SHE HAS BEEN AND IS SERVING ON

269
00:09:33,175 --> 00:09:34,843
MANY EDITORIAL AND ADVISORY

270
00:09:34,843 --> 00:09:36,578
BOARDS AND HAS RECEIVED NUMEROUS

271
00:09:36,578 --> 00:09:42,150
AWARDS INCLUDING THE BRIAN

272
00:09:42,150 --> 00:09:43,685
BOYCOT PRIZE IN RETINAL

273
00:09:43,685 --> 00:09:44,886
NEUROBIOLOGY AND VISUAL

274
00:09:44,886 --> 00:09:46,855
PROCESSING BUT PERHAPS JUST AS

275
00:09:46,855 --> 00:09:48,623
IMPORTANTLY, PROFESSOR FELLER IS

276
00:09:48,623 --> 00:09:50,559
A COMMITTED MENTOR AND TEACHER

277
00:09:50,559 --> 00:09:52,093
AS EVIDENCED BY THE MANY

278
00:09:52,093 --> 00:09:54,830
TEACHING AWARDS SHE HAS

279
00:09:54,830 --> 00:09:57,032
RECEIVED, AND THE GENUINELY

280
00:09:57,032 --> 00:09:58,233
IMPRESSIVE COHORT OF TRAINEES

281
00:09:58,233 --> 00:09:59,868
WHO HAVE GONE ON TO TOP

282
00:09:59,868 --> 00:10:00,735
INSTITUTIONS WORLDWIDE TO MAKE

283
00:10:00,735 --> 00:10:02,504
THEIR OWN SIGNIFICANT

284
00:10:02,504 --> 00:10:05,006
CONTRIBUTIONS TO THE FIELD.

285
00:10:05,006 --> 00:10:06,875
TODAY WE ARE REALLY FORTUNATE TO

286
00:10:06,875 --> 00:10:09,644
HEAR ABOUT HER WORK BY RIDING

287
00:10:09,644 --> 00:10:11,246
THE RETINAL WAVE THROUGH VISUAL

288
00:10:11,246 --> 00:10:12,781
SYSTEM DEVELOPMENT.

289
00:10:12,781 --> 00:10:14,249
PLEASE JOIN ME IN WELCOMING

290
00:10:14,249 --> 00:10:14,783
PROFESSOR FELLER.

291
00:10:14,783 --> 00:10:24,960
[APPLAUSE]

292
00:10:25,827 --> 00:10:26,661
>> OKAY.

293
00:10:26,661 --> 00:10:28,196
WOW, THANK YOU FOR THAT AMAZING

294
00:10:28,196 --> 00:10:28,530
INTRODUCTION.

295
00:10:28,530 --> 00:10:32,167
THANK YOU TO THE FOUNDATION, TO

296
00:10:32,167 --> 00:10:33,668
NATIONAL EYE INSTITUTE FOR

297
00:10:33,668 --> 00:10:35,370
SELECTING ME FOR THIS INCREDIBLE

298
00:10:35,370 --> 00:10:37,372
HONOR AND THIS OPPORTUNITY TO

299
00:10:37,372 --> 00:10:41,109
GIVE THIS PRESENTATION TODAY.

300
00:10:41,109 --> 00:10:44,112
MY LAB IS ENTIRELY FUNDED BY THE

301
00:10:44,112 --> 00:10:45,046
NATIONAL EYE INSTITUTE, SO I

302
00:10:45,046 --> 00:10:48,750
THANK YOU FOR THAT AS WELL.

303
00:10:48,750 --> 00:10:51,152
OKAY, SO TODAY, I AM GOING TO

304
00:10:51,152 --> 00:10:53,889
TALK TO YOU ABOUT THE RESEARCH

305
00:10:53,889 --> 00:10:58,026
THAT'S GOING ON IN THE LAB.

306
00:10:58,026 --> 00:11:00,795
MY GOALS FOR TODAY ARE OUTLINED

307
00:11:00,795 --> 00:11:01,196
HERE.

308
00:11:01,196 --> 00:11:03,398
LET'S SEE, I'M NOT SURE YOU GUYS

309
00:11:03,398 --> 00:11:04,499
CAN SEE THE LITTLE POINTER

310
00:11:04,499 --> 00:11:05,033
THERE?

311
00:11:05,033 --> 00:11:06,234
OKAY.

312
00:11:06,234 --> 00:11:08,103
SO I'M GOING TO START WITH

313
00:11:08,103 --> 00:11:09,971
ACTUALLY A VERY LONG

314
00:11:09,971 --> 00:11:11,072
INTRODUCTION THAT SORT OF

315
00:11:11,072 --> 00:11:12,274
INTRODUCES THE CONCEPT OF

316
00:11:12,274 --> 00:11:12,807
RETINAL WAVES.

317
00:11:12,807 --> 00:11:14,442
I KNOW NOT A LOT OF PEOPLE HERE

318
00:11:14,442 --> 00:11:16,177
WORK ON DEVELOPMENT, AND SO I

319
00:11:16,177 --> 00:11:18,380
JUST AM HOPING THAT THROUGH THIS

320
00:11:18,380 --> 00:11:20,282
INTRODUCTION, YOU CAN SEE HOW

321
00:11:20,282 --> 00:11:22,884
IMPORTANT SORT OF THIS EARLY

322
00:11:22,884 --> 00:11:23,919
DEVELOPMENTAL PHENOMENON IS FOR

323
00:11:23,919 --> 00:11:25,020
SETTING UP LOTS OF CIRCUITS

324
00:11:25,020 --> 00:11:26,354
WITHIN THE VISUAL SYSTEM, AND

325
00:11:26,354 --> 00:11:27,589
THEN I'M GOING TO FOCUS ON A

326
00:11:27,589 --> 00:11:29,858
COUPLE QUESTIONS THAT WE'RE

327
00:11:29,858 --> 00:11:33,361
CURRENTLY WORKING ON IN THE LAB.

328
00:11:33,361 --> 00:11:35,230
AND HOPEFULLY IF THERE'S TIME AT

329
00:11:35,230 --> 00:11:37,766
THE END, ENDING WITH SOME REALLY

330
00:11:37,766 --> 00:11:38,833
VERY NEW WORK WE HAVE

331
00:11:38,833 --> 00:11:40,035
UNDERSTANDING HOW RETINAL WAVES

332
00:11:40,035 --> 00:11:41,703
MIGHT ACTUALLY BE IMPORTANT FOR

333
00:11:41,703 --> 00:11:43,305
SETTING UP THE VASCULATURE

334
00:11:43,305 --> 00:11:44,639
NETWORK WITHIN THE RETINA.

335
00:11:44,639 --> 00:11:46,808
SO WE'LL SEE HOW WE GO ON TIME.

336
00:11:46,808 --> 00:11:47,309
OKAY.

337
00:11:47,309 --> 00:11:49,144
SO WE'RE GOING TO START, AS

338
00:11:49,144 --> 00:11:50,745
YOU'VE HEARD, MY LAB WORKS ON

339
00:11:50,745 --> 00:11:52,180
DEVELOPMENT AND I WANTED TO

340
00:11:52,180 --> 00:11:54,249
START BY SHOWING YOU THIS

341
00:11:54,249 --> 00:11:56,017
SCHEMATIC OF HUMAN BRAIN

342
00:11:56,017 --> 00:11:57,552
DEVELOPMENT BEFORE BIRTH.

343
00:11:57,552 --> 00:12:00,722
AND SO THE EYE AND RETINA

344
00:12:00,722 --> 00:12:01,723
DEVELOP INDEPENDENTLY OF THE

345
00:12:01,723 --> 00:12:03,558
BRAIN.

346
00:12:03,558 --> 00:12:05,427
AND AT THIS INCREDIBLY EARLY

347
00:12:05,427 --> 00:12:06,728
GESTATIONAL AGE IS WHEN THE

348
00:12:06,728 --> 00:12:07,929
OPTIC NERVE EMERGES AND STARTS

349
00:12:07,929 --> 00:12:10,665
TO MAKE CONNECTIONS AND THE

350
00:12:10,665 --> 00:12:12,000
VISUAL SYSTEM STARTS TO WIRE UP.

351
00:12:12,000 --> 00:12:13,068
CLEARLY BEFORE THERE'S ANY SORT

352
00:12:13,068 --> 00:12:14,603
OF VISUAL EXPERIENCE THAT'S

353
00:12:14,603 --> 00:12:18,640
GOING ON FOR THE ANIMAL.

354
00:12:18,640 --> 00:12:19,975
HUMANS ACTUALLY OPEN THEIR EYES

355
00:12:19,975 --> 00:12:22,711
AT AROUND FIVE MONTHS IN

356
00:12:22,711 --> 00:12:23,912
GESTATION, AND THIS IS ABOUT THE

357
00:12:23,912 --> 00:12:25,647
AGE WHEN MICE ARE BORN, AND THIS

358
00:12:25,647 --> 00:12:27,015
IS SORT OF THE STATE -- AND WE

359
00:12:27,015 --> 00:12:28,483
USE MICE AS OUR MODEL ORGANISM

360
00:12:28,483 --> 00:12:31,119
TO STUDY THESE VERY EARLY

361
00:12:31,119 --> 00:12:33,088
DEVELOPMENTAL PHENOMENON.

362
00:12:33,088 --> 00:12:34,956
AND SO AT THIS INCREDIBLY EARLY

363
00:12:34,956 --> 00:12:36,691
STAGE OF DEVELOPMENT, ALTHOUGH

364
00:12:36,691 --> 00:12:39,227
VISION IS NOT PLAYING A ROLE IN

365
00:12:39,227 --> 00:12:40,996
SORT OF SETTING UP ANY

366
00:12:40,996 --> 00:12:41,830
CONNECTIONS, IT TURNS OUT THAT

367
00:12:41,830 --> 00:12:42,931
NEURAL ACTIVITY ACTUALLY IS

368
00:12:42,931 --> 00:12:44,699
PLAYING A ROLE, AND THIS NEURAL

369
00:12:44,699 --> 00:12:46,234
ACTIVITY THAT IS THERE AT THIS

370
00:12:46,234 --> 00:12:48,637
AGE IS SPONTANEOUSLY GENERATED,

371
00:12:48,637 --> 00:12:51,039
AND THE PHENOMENON THAT WE CALL

372
00:12:51,039 --> 00:12:52,007
THE SPONTANEOUS ACTIVITY IS

373
00:12:52,007 --> 00:12:52,874
RETINAL WAVES.

374
00:12:52,874 --> 00:12:54,542
AND SO RETINAL WAVES HAVE BEEN

375
00:12:54,542 --> 00:12:56,711
MEASURED THROUGH A VARIETY OF

376
00:12:56,711 --> 00:12:57,812
DIFFERENT MODALITIES, AND I

377
00:12:57,812 --> 00:12:59,114
WANTED TO GO THROUGH ALL OF THEM

378
00:12:59,114 --> 00:13:00,281
TO SORT OF ALSO GIVE YOU THE

379
00:13:00,281 --> 00:13:01,282
HISTORY OF THE FIELD.

380
00:13:01,282 --> 00:13:04,052
SO RETINA SPONTANEOUS ACTIVITY

381
00:13:04,052 --> 00:13:09,391
WAS FIRST RECORDED IN THE RETINA

382
00:13:09,391 --> 00:13:12,794
BY GALLI AND MAFFEI IN A LAB IN

383
00:13:12,794 --> 00:13:14,896
ITALY WHERE THEY TOOK A FETAL

384
00:13:14,896 --> 00:13:16,498
RAT PUP WHILE IT WAS STILL

385
00:13:16,498 --> 00:13:18,033
ATTACHED BY THE UMBILICAL CORD

386
00:13:18,033 --> 00:13:19,901
TO THE MOTHER, AND THEY DID

387
00:13:19,901 --> 00:13:21,102
RECORDINGS FROM THE RETINA, AND

388
00:13:21,102 --> 00:13:22,404
THEY WERE ABLE TO SEE THAT THERE

389
00:13:22,404 --> 00:13:24,539
WERE THESE SPONTANEOUS BURSTS OF

390
00:13:24,539 --> 00:13:25,840
ACTION POTENTIALS OF ACTIVITY

391
00:13:25,840 --> 00:13:27,242
THAT ARE BEING GENERATED AT THE

392
00:13:27,242 --> 00:13:29,644
RETINA AT THIS EARLY AGE.

393
00:13:29,644 --> 00:13:32,280
SOON AFTER THAT, THERE WAS A

394
00:13:32,280 --> 00:13:33,915
TECHNOLOGY THAT WAS DEVELOPED BY

395
00:13:33,915 --> 00:13:38,720
MARCUS MEISTER WHO COLLABORATED

396
00:13:38,720 --> 00:13:41,022
WITH WONG, WHERE THAT ALLOWED

397
00:13:41,022 --> 00:13:44,859
THEM TO DISSECT THE RETINA,

398
00:13:44,859 --> 00:13:46,828
PLACE IT ON THIS BED OF

399
00:13:46,828 --> 00:13:48,463
ELECTRODES AND MEASURE THE

400
00:13:48,463 --> 00:13:49,531
ACTION POTENTIALS BEING

401
00:13:49,531 --> 00:13:51,066
GENERATED BY THE RETINA, AND YOU

402
00:13:51,066 --> 00:13:53,468
CAN SEE THESE SPONTANEOUS BURSTS

403
00:13:53,468 --> 00:13:55,236
OF ACTION POTENTIALS THAT ARE

404
00:13:55,236 --> 00:13:57,305
PROPAGATING ACROSS THE TISSUE.

405
00:13:57,305 --> 00:13:59,174
MY LAB AND OTHERS, INCLUDING

406
00:13:59,174 --> 00:14:01,643
RACHEL WONG WONG'S LAB, TURNED O

407
00:14:01,643 --> 00:14:02,777
USING IMAGING TO LOOK AT THIS

408
00:14:02,777 --> 00:14:03,111
ACTIVITY.

409
00:14:03,111 --> 00:14:06,081
THIS IS AN EXAMPLE OF AN ARARE,

410
00:14:06,081 --> 00:14:08,783
AGAIN OF A RETINA THAT'S BEEN

411
00:14:08,783 --> 00:14:12,320
DISSECTED AND IT IS SOAKED WITH

412
00:14:12,320 --> 00:14:13,855
A FLUORESCENT DITHAT ALLOWS YOU

413
00:14:13,855 --> 00:14:15,390
TO LOOK AT NEURAL ACTIVITY.

414
00:14:15,390 --> 00:14:16,858
THIS DYE IS PARTICULARLY

415
00:14:16,858 --> 00:14:17,559
SENSITIVE TO CALCIUM.

416
00:14:17,559 --> 00:14:19,127
ONE OF THE NICE THINGS ABOUT

417
00:14:19,127 --> 00:14:21,730
USING THESE FLUORESCENT DYES IS

418
00:14:21,730 --> 00:14:24,032
YOU CAN IMAGE OVER THESE VERY

419
00:14:24,032 --> 00:14:25,700
LARGE AREAS THEE ARE RECENT

420
00:14:25,700 --> 00:14:27,635
MOVIES TAKEN BY THE LAB WHERE

421
00:14:27,635 --> 00:14:29,037
WE'VE DISSECTED THE ENTIRE

422
00:14:29,037 --> 00:14:32,707
RETINA OUT OF A MOUSE PUP AND

423
00:14:32,707 --> 00:14:34,709
BEEN ABLE TO LOOK AT WHAT THE

424
00:14:34,709 --> 00:14:36,644
SPONTANEOUS ACTIVITY LOOKS LIKE

425
00:14:36,644 --> 00:14:37,712
ACROSS THE ENTIRE DISSECTED

426
00:14:37,712 --> 00:14:40,348
RETINA.

427
00:14:40,348 --> 00:14:41,549
SO THIS ROBUST ACTIVITY IS

428
00:14:41,549 --> 00:14:42,884
THERE, WE KIND OF THINK OF IT AS

429
00:14:42,884 --> 00:14:44,853
A TEST PATTERN THAT'S BEING

430
00:14:44,853 --> 00:14:48,356
GENERATED IN THE RETINA THAT'S

431
00:14:48,356 --> 00:14:49,324
PROPAGATING UP THROUGH THE

432
00:14:49,324 --> 00:14:50,024
VISUAL SYSTEM THAT'S IMPORTANT

433
00:14:50,024 --> 00:14:51,392
FOR THINGS TO GET WIRED UP

434
00:14:51,392 --> 00:14:52,160
DURING DEVELOPMENT.

435
00:14:52,160 --> 00:14:54,896
SO IT'S BEEN THIS QUESTION THAT

436
00:14:54,896 --> 00:14:56,531
HAS REALLY FASCINATE AND DRIVEN

437
00:14:56,531 --> 00:14:58,299
OUR RESEARCH FOR A LONG TIME.

438
00:14:58,299 --> 00:15:00,168
SO LET'S JUST TAKE A STEP

439
00:15:00,168 --> 00:15:01,669
BACK -- OH, I WANTED TO SAY THAT

440
00:15:01,669 --> 00:15:03,772
ALTHOUGH WE STUDY THIS IN THE

441
00:15:03,772 --> 00:15:05,840
RETINA, IT TURNS OUT THIS

442
00:15:05,840 --> 00:15:06,708
PHENOMENON OF SPONTANEOUSLY

443
00:15:06,708 --> 00:15:09,010
GENERATING THESE KIND OF BURSTS

444
00:15:09,010 --> 00:15:10,545
OF ACTIVITY ARE FOUND THROUGHOUT

445
00:15:10,545 --> 00:15:11,846
THE DEVELOPING NERVOUS SYSTEM.

446
00:15:11,846 --> 00:15:13,948
SO IN ALL OF THESE CIRCUITS,

447
00:15:13,948 --> 00:15:17,218
RETINA, SPINAL CORD,

448
00:15:17,218 --> 00:15:18,419
HIPPOCAMPUS, CEREBELLUM,

449
00:15:18,419 --> 00:15:20,288
COCHLEA, THEY ALL GENERATE VERY

450
00:15:20,288 --> 00:15:21,589
SIMILAR, REMARKABLY SIMILAR

451
00:15:21,589 --> 00:15:23,892
ACTIVITY, BURSTS OF ACTION

452
00:15:23,892 --> 00:15:24,893
POTENTIALS, CORRELATED ACROSS

453
00:15:24,893 --> 00:15:26,394
LARGE NUMBERS OF CELLS THAT

454
00:15:26,394 --> 00:15:27,662
OCCUR ABOUT ONCE A MINUTE.

455
00:15:27,662 --> 00:15:29,564
SO VERY INFREQUENT, BUT THESE

456
00:15:29,564 --> 00:15:30,999
LARGE POPULATION EVENTS.

457
00:15:30,999 --> 00:15:32,634
AND DESPITE THE FACT THAT THESE

458
00:15:32,634 --> 00:15:34,035
CIRCUITS ARE INCREDIBLY

459
00:15:34,035 --> 00:15:36,371
DIFFERENT IN THEIR MECHANISMS BY

460
00:15:36,371 --> 00:15:39,641
WHICH THEY GENERATE THIS

461
00:15:39,641 --> 00:15:40,842
ACTIVITY, WHETHER OR NOT THERE'S

462
00:15:40,842 --> 00:15:41,943
EXCITATION OR INHIBITION OR

463
00:15:41,943 --> 00:15:43,378
SOMETIMES EVEN TRANSIENT ORGANS

464
00:15:43,378 --> 00:15:44,813
THAT ARE THERE TO HELP MEDIATE

465
00:15:44,813 --> 00:15:46,114
THIS ACTIVITY, THEY ALL HAVE

466
00:15:46,114 --> 00:15:50,919
THIS KIND OF SIMILAR FUNCTION SO

467
00:15:50,919 --> 00:15:52,453
WE THINK OF THIS AS NOT BEING

468
00:15:52,453 --> 00:15:53,555
UNIQUE THROUGH THE VISUAL

469
00:15:53,555 --> 00:15:54,856
SYSTEM, IT'S FOUND THROUGHOUT

470
00:15:54,856 --> 00:15:56,090
THE NERVOUS SYSTEM, WE KIND OF

471
00:15:56,090 --> 00:15:57,392
THINK OF IT AS THE BRAIN IS

472
00:15:57,392 --> 00:15:58,359
GETTING WIRED UP, THIS IS A

473
00:15:58,359 --> 00:15:59,661
PERIOD OF ITS DEVELOPMENT THAT

474
00:15:59,661 --> 00:16:02,630
IS IMPORTANT TO TAKE INTO

475
00:16:02,630 --> 00:16:03,164
CONSIDERATION.

476
00:16:03,164 --> 00:16:04,165
BUT WE WILL BE FOCUSING ON HOW

477
00:16:04,165 --> 00:16:05,366
THIS ACTIVITY IS GENERATED IN

478
00:16:05,366 --> 00:16:07,001
THE RETINA, AND WHAT ROLE IT

479
00:16:07,001 --> 00:16:08,203
PLAYS IN VISUAL SYSTEM

480
00:16:08,203 --> 00:16:10,505
DEVELOPMENT.

481
00:16:10,505 --> 00:16:12,407
SO I CERTAINLY DON'T NEED TO

482
00:16:12,407 --> 00:16:13,875
TELL A NATIONAL EYE INSTITUTE

483
00:16:13,875 --> 00:16:15,643
AUDIENCE WHAT THE RETINA IS, BUT

484
00:16:15,643 --> 00:16:16,945
JUST IN CASE THERE'S SOMEONE OUT

485
00:16:16,945 --> 00:16:17,846
THERE IN THE WORLD WHERE THIS IS

486
00:16:17,846 --> 00:16:20,448
NEW TO THEM, THE WAY THAT VISION

487
00:16:20,448 --> 00:16:22,517
BEGINS IS THERE'S LIGHT PHOTONS

488
00:16:22,517 --> 00:16:24,052
REFLECTED OFF OF OBJECTS OUT IN

489
00:16:24,052 --> 00:16:24,752
THE VISUAL WORLD.

490
00:16:24,752 --> 00:16:26,120
THERE'S A BIG LENS IN YOUR EYE

491
00:16:26,120 --> 00:16:28,489
THAT FOCUSES THAT LIGHT ON TO

492
00:16:28,489 --> 00:16:29,958
THE RETINA, WHICH IS THIS LITTLE

493
00:16:29,958 --> 00:16:31,159
NEURAL TISSUE THAT LINES THE

494
00:16:31,159 --> 00:16:32,393
BACK OF THE EYE.

495
00:16:32,393 --> 00:16:36,431
THE RETINA IS NOT JUST A PIXEL

496
00:16:36,431 --> 00:16:38,066
ATED CAMERA BUT IT IS A LITTLE

497
00:16:38,066 --> 00:16:39,601
NEURAL CIRCUIT WHOSE JOB IS TO

498
00:16:39,601 --> 00:16:41,569
EXTRACT SALIENT FEATURES OF THE

499
00:16:41,569 --> 00:16:43,538
VISUAL WORLD SO THAT IT CAN SEND

500
00:16:43,538 --> 00:16:44,639
IT UP TO THE BRAIN.

501
00:16:44,639 --> 00:16:45,607
SO LIGHT PASSES THROUGH THIS

502
00:16:45,607 --> 00:16:48,443
CHUNK OF NEURAL TISSUE,

503
00:16:48,443 --> 00:16:49,544
ACTIVATES THE PHOTORECEPTORS OF

504
00:16:49,544 --> 00:16:50,311
THE BACK OF THE EYE.

505
00:16:50,311 --> 00:16:52,013
THERE ARE A SERIES OF

506
00:16:52,013 --> 00:16:53,715
INTERNEURONS THAT PROCESS THAT

507
00:16:53,715 --> 00:16:54,782
INFORMATION FROM THE

508
00:16:54,782 --> 00:16:57,752
PHOTORECEPTORS, AND THAT

509
00:16:57,752 --> 00:16:59,387
INFORMATION CONVERGES ON THE

510
00:16:59,387 --> 00:17:00,822
RETINAL GANGLION CELLS AND THERE

511
00:17:00,822 --> 00:17:03,091
ARE AXONS THAT FORM THE OPTIC

512
00:17:03,091 --> 00:17:05,627
NEVNERVE THAT GO UP TO THE BRAI.

513
00:17:05,627 --> 00:17:06,494
SO DURING THIS PERIOD OF

514
00:17:06,494 --> 00:17:07,395
DEVELOPMENT WHEN THERE ARE

515
00:17:07,395 --> 00:17:09,063
RETINAL WAVES, THE RETINA IS

516
00:17:09,063 --> 00:17:10,665
QUITE IMMATURE, AND SO HERE WE

517
00:17:10,665 --> 00:17:14,135
HAVE THE ADULT ON THE LEFT, BUT

518
00:17:14,135 --> 00:17:15,270
THIS IS SORT OF WHAT WE'RE

519
00:17:15,270 --> 00:17:16,571
LOOKING AT ON THE RIGHT IS WHAT

520
00:17:16,571 --> 00:17:20,275
HAPPENS BEFORE VISION IS

521
00:17:20,275 --> 00:17:20,708
POSSIBLE.

522
00:17:20,708 --> 00:17:22,343
SO THE OUTER RETINA DEVELOPS,

523
00:17:22,343 --> 00:17:23,244
THE PHOTORECEPTORS ARE

524
00:17:23,244 --> 00:17:24,512
DEVELOPING, THEY HAVE VERY SMALL

525
00:17:24,512 --> 00:17:27,048
OUOUTER SEGMENTS, THEY'RE STARTG

526
00:17:27,048 --> 00:17:29,150
TO FORM SYNAPSES WITH SOME POST

527
00:17:29,150 --> 00:17:30,251
SYNAPTIC PARTNERS CALLED

528
00:17:30,251 --> 00:17:31,653
HORIZONTAL CELLS.

529
00:17:31,653 --> 00:17:34,822
THE GANGLION CELLS ARE THE FIRST

530
00:17:34,822 --> 00:17:36,424
TO MATURE, THEY MY GATE TO THE

531
00:17:36,424 --> 00:17:37,792
RIGHT PART OF THE RETINA, THEY

532
00:17:37,792 --> 00:17:39,093
SEND THEIR AXONS UP TO THE

533
00:17:39,093 --> 00:17:40,094
BRAIN, ALL THE WAY UP THERE

534
00:17:40,094 --> 00:17:41,629
WHILE THE REST OF THE RETINA IS

535
00:17:41,629 --> 00:17:42,931
UNDERGOING THIS DEVELOPMENT.

536
00:17:42,931 --> 00:17:44,132
AND THEY'RE STARTING TO FORM

537
00:17:44,132 --> 00:17:48,169
SNAP TIB CIRCUITSYNAPTIC CIRCUIT

538
00:17:48,169 --> 00:17:49,270
IMPORTANTLY AT THESE EARLY

539
00:17:49,270 --> 00:17:50,672
STAGES OF DEVELOPMENT, THESE

540
00:17:50,672 --> 00:17:51,906
NEURONS THAT CONNECT THE OUTER

541
00:17:51,906 --> 00:17:53,541
RETINA TO THE INNER RETINA, THAT

542
00:17:53,541 --> 00:17:55,076
CONNECT THOSE PHOTORECEPTORS TO

543
00:17:55,076 --> 00:17:56,911
THE GANGLION CELLS HAVE NOT

544
00:17:56,911 --> 00:17:58,513
FORMED THEIR SYNAPSES, SO EVEN

545
00:17:58,513 --> 00:18:00,315
IF YOU CAN GET A WEAK, LIGHT

546
00:18:00,315 --> 00:18:03,718
RESPONSE EARLY IN DEVELOPMENT,

547
00:18:03,718 --> 00:18:05,353
THE RETINAL GANGLION CELLS ARE

548
00:18:05,353 --> 00:18:08,957
BLIND TO THAT LIGHT, BUT INSTEAD

549
00:18:08,957 --> 00:18:10,591
THEY'RE GENERATING THIS ACTIVITY

550
00:18:10,591 --> 00:18:13,761
SPONTANEOUSLY.

551
00:18:13,761 --> 00:18:14,762
SO ONE OF THE WAYS THAT WE LOOK

552
00:18:14,762 --> 00:18:16,264
AT THIS TO SORT OF EXPLAIN HOW

553
00:18:16,264 --> 00:18:17,699
WE DO THESE EXPERIMENTS IS I

554
00:18:17,699 --> 00:18:21,002
JUST WANTED TO -- IS VIA

555
00:18:21,002 --> 00:18:23,438
IMAGING, SO WHAT WE DO IS WE

556
00:18:23,438 --> 00:18:24,605
DISSECT OUT RETINAS, WE PLACE

557
00:18:24,605 --> 00:18:25,907
THEM IN A CHAMBER THAT'S SHOWN

558
00:18:25,907 --> 00:18:27,542
HERE IN THE LOWER LEFT, WE

559
00:18:27,542 --> 00:18:29,077
PERFUSE THE RETINA WITH THE

560
00:18:29,077 --> 00:18:30,178
SOLUTIONS THAT IT WOULD NORMALLY

561
00:18:30,178 --> 00:18:32,480
BE EXPOSED TO WHEN IT'S IN THE

562
00:18:32,480 --> 00:18:32,814
EYE.

563
00:18:32,814 --> 00:18:35,316
WE PUT IT UNDER A MICROSCOPE

564
00:18:35,316 --> 00:18:36,517
OBJECTIVE AND WE HAVE A

565
00:18:36,517 --> 00:18:37,552
SPECIALIZED MICROSCOPE IN THIS

566
00:18:37,552 --> 00:18:40,121
CASE CALLED A 2 PHOTON

567
00:18:40,121 --> 00:18:43,958
MICROSCOPE THAT ALLOWS US TO

568
00:18:43,958 --> 00:18:45,293
RECORD FLUORESCENT SIGNALS

569
00:18:45,293 --> 00:18:47,362
GENERATED BY THE RETINA, AND IN

570
00:18:47,362 --> 00:18:48,730
THIS CASE THOSE FLUORESCENT

571
00:18:48,730 --> 00:18:49,664
SIGNALS ARE GENERATED BECAUSE

572
00:18:49,664 --> 00:18:52,266
WE'VE SOAKED THE RETINA IN A

573
00:18:52,266 --> 00:18:53,568
FLUORESCENT DYE THAT GOES INTO

574
00:18:53,568 --> 00:18:55,870
THE CELLS AND ARE SENSITIVE TO

575
00:18:55,870 --> 00:18:56,537
CALCIUM.

576
00:18:56,537 --> 00:18:57,939
SO WE'RE GOING TO NOW LOOK AT

577
00:18:57,939 --> 00:19:00,475
MOVIES THAT ARE GENERATED BY

578
00:19:00,475 --> 00:19:03,311
IMAGING AT THE GANGLION CELL

579
00:19:03,311 --> 00:19:05,046
LAYER, AND JUST TO GIVE YOU A

580
00:19:05,046 --> 00:19:06,381
SENSE, THIS IS -- IF YOU LOOK AT

581
00:19:06,381 --> 00:19:07,482
THE WHOLE RETINA, THIS IS

582
00:19:07,482 --> 00:19:08,783
ROUGHLY THE FIELD OF VIEW OVER

583
00:19:08,783 --> 00:19:11,185
WHICH WE IMAGE, AND THIS IS THE

584
00:19:11,185 --> 00:19:14,355
SAME MOVIE THAT YOU SAW BEFORE.

585
00:19:14,355 --> 00:19:15,456
EXCEPT THIS MOVIE ISN'T PLAYING.

586
00:19:15,456 --> 00:19:17,091
IT WAS THE SAME MOVIE YOU SAW

587
00:19:17,091 --> 00:19:19,727
BEFORE, WI WHERE YOU COULD SEE E

588
00:19:19,727 --> 00:19:21,462
SPONTANEOUS INCREASES IN

589
00:19:21,462 --> 00:19:22,463
FLUORESCENCE FOR PROPAGATING

590
00:19:22,463 --> 00:19:23,531
ACTIVITY ACROSS THE TISSUE.

591
00:19:23,531 --> 00:19:24,499
SORRY ABOUT THAT MOVIE NOT

592
00:19:24,499 --> 00:19:29,137
WORKING.

593
00:19:29,137 --> 00:19:31,439
SO MY LAB IS SUPER INTERESTED IN

594
00:19:31,439 --> 00:19:32,840
HOW THIS IS BEING GENERATED.

595
00:19:32,840 --> 00:19:34,042
THIS IS CLEARLY SOMETHING THE

596
00:19:34,042 --> 00:19:36,477
ADULT RETINA DOES NOT DO, IF WE

597
00:19:36,477 --> 00:19:37,879
HAD SPONTANEOUS DEPOLARIZATIONS

598
00:19:37,879 --> 00:19:39,614
PROPAGATING AGAINST OUR RETINAS,

599
00:19:39,614 --> 00:19:40,815
VISION WOULD BE VERY CONFUSING

600
00:19:40,815 --> 00:19:41,582
SO THERE'S SOMETHING ABOUT THE

601
00:19:41,582 --> 00:19:42,583
DEVELOPING RETINA AT THIS STAGE

602
00:19:42,583 --> 00:19:43,851
OF DEVELOPMENT THAT GENERATES

603
00:19:43,851 --> 00:19:44,552
THIS ACTIVITY.

604
00:19:44,552 --> 00:19:46,621
YOU NEED SOMETHING TO

605
00:19:46,621 --> 00:19:47,221
SPONTANEOUSLY DEPOLARIZATION,

606
00:19:47,221 --> 00:19:48,589
YOU NEED SOMETHING TO CARRY --

607
00:19:48,589 --> 00:19:51,893
TO PROPAGATE THAT ACTIVITY LAD

608
00:19:51,893 --> 00:19:53,294
LATERALLY ACROSS THE RETINA.

609
00:19:53,294 --> 00:19:56,030
SO TO SORT OF GET AT THIS

610
00:19:56,030 --> 00:19:57,799
PHENOMENA, WE STARTED USING

611
00:19:57,799 --> 00:19:58,566
PHYSIOLOGICAL TECHNIQUES.

612
00:19:58,566 --> 00:20:01,069
A BIG ONE THAT WE USE IS CALLED

613
00:20:01,069 --> 00:20:02,937
WHOLE CELL VOLTAGE CLAMP

614
00:20:02,937 --> 00:20:03,237
RECORDINGS.

615
00:20:03,237 --> 00:20:05,006
THIS IS WHERE WE CAN STICK AN

616
00:20:05,006 --> 00:20:06,541
ELECTRODE ON AN INDIVIDUAL

617
00:20:06,541 --> 00:20:08,042
GANGLION CELL AND THESE

618
00:20:08,042 --> 00:20:08,943
DEFLECTIONS THAT YOU'RE LOOKING

619
00:20:08,943 --> 00:20:12,980
AT ON THE BOTTOM TRACE REPRESENT

620
00:20:12,980 --> 00:20:14,048
EVIDENT THAT THERE ARE SYNAPTIC

621
00:20:14,048 --> 00:20:14,949
CIRCUITS THAT EXIST AT THIS

622
00:20:14,949 --> 00:20:15,283
TIME.

623
00:20:15,283 --> 00:20:16,918
SO THESE ARE CURRENTS THAT ARE

624
00:20:16,918 --> 00:20:19,554
DUE TO EXCITATORY

625
00:20:19,554 --> 00:20:20,955
NEUROTRANSMITTER, BINDING TO THE

626
00:20:20,955 --> 00:20:21,756
RECEPTORS ON THE CELL, SO

627
00:20:21,756 --> 00:20:23,324
CIRCUIT ARE STARTING TO EMERGE.

628
00:20:23,324 --> 00:20:25,460
WE CAN TAKE A SECOND ELECTRODE.

629
00:20:25,460 --> 00:20:27,528
THESE ARE EXPERIMENTS THAT WERE

630
00:20:27,528 --> 00:20:28,963
DONE BY BLANK INSHIP WHILE A

631
00:20:28,963 --> 00:20:30,331
STUDENT IN THE LAP WHERE WE CAN

632
00:20:30,331 --> 00:20:31,466
LOOK AT THE MEMBRANE POTENTIAL

633
00:20:31,466 --> 00:20:32,700
CHANGES IN CELLS AND YOU CAN SEE

634
00:20:32,700 --> 00:20:34,202
THAT THEY FIRE BURST OF ACTION

635
00:20:34,202 --> 00:20:35,403
POTENTIALS AND IF WE

636
00:20:35,403 --> 00:20:36,504
SIMULTANEOUSLY DO IMAGING AT

637
00:20:36,504 --> 00:20:40,274
THAT TIME, YOU SEE THAT THERE'S

638
00:20:40,274 --> 00:20:41,209
INCREASES IN FLUORESCENCE THAT

639
00:20:41,209 --> 00:20:44,178
YOU SAW IN THE MOVIES DUE TO

640
00:20:44,178 --> 00:20:45,279
ACTION POTENTIALS WHICH ARE DUE

641
00:20:45,279 --> 00:20:47,815
TO A BARRAGE OF EXCITATORY

642
00:20:47,815 --> 00:20:48,483
SYNAPTIC CURRENTS ON TO THE

643
00:20:48,483 --> 00:20:48,916
CELLS.

644
00:20:48,916 --> 00:20:50,985
SO WE KNOW THAT THIS ACTIVITY IS

645
00:20:50,985 --> 00:20:52,620
GENERATED BY THIS KIND OF EARLY

646
00:20:52,620 --> 00:20:56,090
SYNAPTIC CIRCUITS.

647
00:20:56,090 --> 00:20:57,525
MY LAB HAS SPENT A LOT OF TIME

648
00:20:57,525 --> 00:20:58,626
SORT OF IDENTIFYING WHAT THESE

649
00:20:58,626 --> 00:20:59,193
CIRCUITS ARE.

650
00:20:59,193 --> 00:20:59,927
AND ONE OF THE THINGS THAT I

651
00:20:59,927 --> 00:21:01,696
FIND REALLY -- HAVE BEEN REALLY

652
00:21:01,696 --> 00:21:03,331
FASCINATING ABOUT THIS QUESTION

653
00:21:03,331 --> 00:21:04,765
IS THAT RETINAL WAVES PERSIST

654
00:21:04,765 --> 00:21:07,168
FOR AN INCREDIBLY LONG PERIOD OF

655
00:21:07,168 --> 00:21:07,602
DEVELOPMENT.

656
00:21:07,602 --> 00:21:08,803
AND IN FACT I'LL JUST REVEAL ALL

657
00:21:08,803 --> 00:21:11,339
OF THESE.

658
00:21:11,339 --> 00:21:12,640
AND DURING THIS PERIOD OF

659
00:21:12,640 --> 00:21:13,741
DEVELOPMENT, THE RETINA ITSELF

660
00:21:13,741 --> 00:21:16,144
IS UNDERGOING A TREMENDOUS

661
00:21:16,144 --> 00:21:17,645
AMOUNT OF DEVELOPMENT.

662
00:21:17,645 --> 00:21:21,149
SO THE EARLIEST AGE AT WHICH WE

663
00:21:21,149 --> 00:21:23,584
SEE THESE RETINAL WAVES IN MICE

664
00:21:23,584 --> 00:21:26,854
IS EMBRYONIC DAY 16, WHICH IS

665
00:21:26,854 --> 00:21:28,723
WHEN THE RETINA -- WHERE THE

666
00:21:28,723 --> 00:21:29,557
GANGLION CELLS ARE REALLY THE

667
00:21:29,557 --> 00:21:31,092
ONLY CELLS THAT HAVE

668
00:21:31,092 --> 00:21:31,893
DIFFERENTIATED, THEY SENT THEIR

669
00:21:31,893 --> 00:21:33,161
AXONS TO THE BRAIN, AND THE REST

670
00:21:33,161 --> 00:21:36,697
OF THE RETINA IS KIND OF A

671
00:21:36,697 --> 00:21:37,698
DIVIDING NEUROEPITHELIAL LAYER

672
00:21:37,698 --> 00:21:40,201
WITH JUST A FEW CELLS THAT ARE

673
00:21:40,201 --> 00:21:41,636
STARTING TO MATURE, THAT ARE

674
00:21:41,636 --> 00:21:46,674
SHOWN THERE IN THE BLUE.

675
00:21:46,674 --> 00:21:48,409
THEN WAVES PERSIST UNTIL

676
00:21:48,409 --> 00:21:52,013
POSTNATAL DAY 12, OR 13 IN MICE,

677
00:21:52,013 --> 00:21:53,047
AND THAT'S WHEN MICE OPEN THEIR

678
00:21:53,047 --> 00:21:53,314
EYES.

679
00:21:53,314 --> 00:21:54,982
WHEN A MOUSE OPENS THEIR EYES,

680
00:21:54,982 --> 00:21:55,516
THEY CAN SEE.

681
00:21:55,516 --> 00:21:57,251
SO THE REST OF THE CIRCUIT IS

682
00:21:57,251 --> 00:21:58,686
MATURE, AND SO AT THIS STAGE, AT

683
00:21:58,686 --> 00:22:02,089
THE LATER STAGE OF RETINAL

684
00:22:02,089 --> 00:22:02,957
WAVES, ALL OF THE CELLS ARE

685
00:22:02,957 --> 00:22:04,258
WIRED IN, SO THERE'S A BRIEF

686
00:22:04,258 --> 00:22:05,059
PERIOD OF TIME WHERE THERE'S

687
00:22:05,059 --> 00:22:06,027
KIND OF VISION THAT'S COMING

688
00:22:06,027 --> 00:22:08,429
THROUGH THE CLOSED EYELIDS, AND

689
00:22:08,429 --> 00:22:10,064
RETINAL WAVES ARE BEING

690
00:22:10,064 --> 00:22:10,498
GENERATED.

691
00:22:10,498 --> 00:22:14,235
AND THEN THERE'S THIS MEDIUM

692
00:22:14,235 --> 00:22:15,770
TIME WHERE WE SPENT MOST OF OUR

693
00:22:15,770 --> 00:22:17,505
EFFORTS WHERE WE'VE IDENTIFIED A

694
00:22:17,505 --> 00:22:22,143
CIRCUIT THAT'S MEDIATED BY

695
00:22:22,143 --> 00:22:23,444
ACETYLCHOLINE THAT'S THERE

696
00:22:23,444 --> 00:22:24,512
TRANSIENTLY DURING DEVELOPMENT.

697
00:22:24,512 --> 00:22:26,480
SO WE KNOW THAT THERE'S A

698
00:22:26,480 --> 00:22:27,215
PARTICULAR CLASS OF CELLS,

699
00:22:27,215 --> 00:22:29,650
THEY'RE CALLED STARBURST AM KRON

700
00:22:29,650 --> 00:22:30,618
CELLS, YOU'RE GOING TO HEAR

701
00:22:30,618 --> 00:22:32,687
ABOUT THEM QUITE A FEW TIMES

702
00:22:32,687 --> 00:22:33,821
TODAY IN THE TALK.

703
00:22:33,821 --> 00:22:34,989
IT'S A BEAUTIFUL INTERNEURON

704
00:22:34,989 --> 00:22:37,858
THAT RELEASES ACETYLCHOLINE.

705
00:22:37,858 --> 00:22:40,761
THEY SPONTANEOUSLY DEPOLARIZE

706
00:22:40,761 --> 00:22:42,663
VERY INFREQUENTLY, THEY RELEASE

707
00:22:42,663 --> 00:22:44,966
ACETYLCHOLINE AND THAT

708
00:22:44,966 --> 00:22:47,568
ACETYLCHOLINE ACTIVATES

709
00:22:47,568 --> 00:22:48,903
NICOTINIC RECEPTORS AND THAT IS

710
00:22:48,903 --> 00:22:50,204
WHAT DRIVES RETINAL WAVE

711
00:22:50,204 --> 00:22:53,274
PROPAGATION.

712
00:22:53,274 --> 00:22:55,009
SO THESE STAGES OF DEVELOPMENT,

713
00:22:55,009 --> 00:22:56,978
OR THIS SPANS ALMOST THREE WEEKS

714
00:22:56,978 --> 00:23:00,147
OF DEVELOPMENT, AND THE CIRCUITS

715
00:23:00,147 --> 00:23:01,682
THAT ARE MEDIATING WAVES ARE

716
00:23:01,682 --> 00:23:02,783
CHANGING AND SO DURING THAT TIME

717
00:23:02,783 --> 00:23:04,652
AS THE CIRCUITS CHANGE, ACTUALLY

718
00:23:04,652 --> 00:23:05,953
THE PROPAGATION PROPERTIES OF

719
00:23:05,953 --> 00:23:06,621
THE WAVES CHANGE.

720
00:23:06,621 --> 00:23:09,724
SO WHAT YOU'RE LOOKING AT HERE

721
00:23:09,724 --> 00:23:11,092
ARE WAVES ON THE LEFT THAT ARE

722
00:23:11,092 --> 00:23:13,194
SHOWN ON EMBRYONIC DAY 17 SO

723
00:23:13,194 --> 00:23:15,229
RIGHT BEFORE THE MOUSE IS BORN,

724
00:23:15,229 --> 00:23:18,666
IN THE MIDDLE OF THE FIRST

725
00:23:18,666 --> 00:23:20,701
POSTNATAL WEEK AND IN THE SECOND

726
00:23:20,701 --> 00:23:23,004
POSE NATAL WEEK AND IN THE TOP

727
00:23:23,004 --> 00:23:25,206
ARE WHAT WAVES LOOK LIKE IN

728
00:23:25,206 --> 00:23:25,473
REALTIME.

729
00:23:25,473 --> 00:23:27,742
AND THE BOTTOM IS THE

730
00:23:27,742 --> 00:23:28,709
SEGMENTATION ALGORITHM THAT WAS

731
00:23:28,709 --> 00:23:29,410
WRITTEN TO IDENTIFY THE WAVES

732
00:23:29,410 --> 00:23:31,078
AND YOU CAN SEE THAT AS THE

733
00:23:31,078 --> 00:23:32,546
CIRCUITS THAT MEDIATE WAVES

734
00:23:32,546 --> 00:23:33,648
CHANGE, ACTUALLY THE PROPERTIES

735
00:23:33,648 --> 00:23:36,150
OF THE WAVES CHANGE A LOT.

736
00:23:36,150 --> 00:23:37,718
SO IN THE STAGE TWO, WHICH WE

737
00:23:37,718 --> 00:23:39,220
SPENT -- THIS IS THIS

738
00:23:39,220 --> 00:23:40,087
CHOLINERGIC CIRCUIT, WE THINK OF

739
00:23:40,087 --> 00:23:41,389
THEM AS WAVES ON THE BEACH, YOU

740
00:23:41,389 --> 00:23:43,691
MAY NOTICE THERE'S BEEN ONE WAVE

741
00:23:43,691 --> 00:23:46,994
THAT'S PROPAGATING ACROSS THAT

742
00:23:46,994 --> 00:23:50,164
ENTIRE WAVE WHILE I'VE BEEN

743
00:23:50,164 --> 00:23:51,999
TALKING, THEY STILL PROPAGATE

744
00:23:51,999 --> 00:23:53,968
RATHER STOWLY, WHILE AT STAGE

745
00:23:53,968 --> 00:23:55,303
III, THEY'RE RAPID, SMALL AND

746
00:23:55,303 --> 00:23:56,937
MORE CIRCUITOUS.

747
00:23:56,937 --> 00:23:58,472
SO ALL OF THESE PROPERTIES OF

748
00:23:58,472 --> 00:24:00,541
THE WAVES ARE REALLY CHANGING AS

749
00:24:00,541 --> 00:24:02,743
THE CIRCUITS THAT MEDIATE

750
00:24:02,743 --> 00:24:03,711
CHANGE, AND I WILL ARGUE THAT

751
00:24:03,711 --> 00:24:05,813
THESE CHANGING PROPERTIES OF THE

752
00:24:05,813 --> 00:24:08,316
WAVES ARE SERVING -- SENDING

753
00:24:08,316 --> 00:24:09,650
DIFFERENT SIGNALS UP TO THE

754
00:24:09,650 --> 00:24:11,252
BRAIN THAT ARE CRITICAL FOR

755
00:24:11,252 --> 00:24:13,020
WHATEVER IS DEVELOPING IN THE

756
00:24:13,020 --> 00:24:14,355
VISUAL SYSTEM AT THAT TIME.

757
00:24:14,355 --> 00:24:16,190
SO TO CONVINCE YOU THAT THIS

758
00:24:16,190 --> 00:24:18,259
ACTIVITY ACTUALLY IS PROPAGATING

759
00:24:18,259 --> 00:24:19,794
UP THROUGH THE BRAIN, THESE ARE

760
00:24:19,794 --> 00:24:21,329
ACTUALLY EXPERIMENTS THAT WERE

761
00:24:21,329 --> 00:24:24,598
DONE BY MIKE CRER'S LAB WHO WAS

762
00:24:24,598 --> 00:24:27,468
ABLE TO DO RECORDINGS IN THE

763
00:24:27,468 --> 00:24:29,103
SUPERIOR COLLICULUS, WHILE THE

764
00:24:29,103 --> 00:24:30,071
MOUSE IS EXPERIENCING RETINAL

765
00:24:30,071 --> 00:24:30,404
WAVES.

766
00:24:30,404 --> 00:24:33,808
SO WHAT YOU'RE LOOKING AT HERE,

767
00:24:33,808 --> 00:24:35,009
WHAT HE'S DONE IS TWO DIFFERENT

768
00:24:35,009 --> 00:24:35,676
KINDS OF EXPERIMENTS.

769
00:24:35,676 --> 00:24:37,745
ONE IN WHICH HE'S PUT A CALCIUM

770
00:24:37,745 --> 00:24:39,146
DYE IN THE RETINA LIKE WE HAVE,

771
00:24:39,146 --> 00:24:42,783
BUT NOW THAT GOES DOWN THE AXON,

772
00:24:42,783 --> 00:24:44,485
THE AXONS PROJECT TO THE SURFACE

773
00:24:44,485 --> 00:24:46,287
OF THE COLLICULUS, AND YOU CAN

774
00:24:46,287 --> 00:24:48,923
SEE THAT THEY HAVE VERY SIMILAR

775
00:24:48,923 --> 00:24:49,890
PROPAGATION PROPERTIES TO WHAT'S

776
00:24:49,890 --> 00:24:50,658
HAPPENING IN THE RETINA, BUT

777
00:24:50,658 --> 00:24:52,860
THEN HE CAN ALSO PUT A CALCIUM

778
00:24:52,860 --> 00:24:54,595
DYE IN THE POST SYNAPTIC CELLS

779
00:24:54,595 --> 00:24:55,596
IN THE COLLICULUS AND THAT'S

780
00:24:55,596 --> 00:24:57,231
SHOWN IN THE BOTTOM, SEE IF WE

781
00:24:57,231 --> 00:25:04,572
CAN PLAY THAT AGAIN.

782
00:25:04,572 --> 00:25:06,674
WHERE YOU CAN SEE THIS ACTIVITY

783
00:25:06,674 --> 00:25:08,943
GENERATED BY THE RETINA IS VERY

784
00:25:08,943 --> 00:25:10,678
RELIABLY RADIATING DOWN TO THE

785
00:25:10,678 --> 00:25:12,313
COLLICULUS AND DEPOSING THE

786
00:25:12,313 --> 00:25:12,780
COLLICULUS.

787
00:25:12,780 --> 00:25:15,082
THEY PROPAGATE TO THE LGN, TO

788
00:25:15,082 --> 00:25:16,417
THE PRIMARY VISUAL CORTEX, AND

789
00:25:16,417 --> 00:25:17,351
IN FACT THERE'S BEEN SIGNATURES

790
00:25:17,351 --> 00:25:19,086
OF RETINAL WAVES ACTIVATING

791
00:25:19,086 --> 00:25:22,056
LARGE AREAS OF VISUAL CORTEX,

792
00:25:22,056 --> 00:25:24,024
BOTH DURING THESE VERY EARLY

793
00:25:24,024 --> 00:25:26,093
STAGE TWO WAVES AND STAGE III

794
00:25:26,093 --> 00:25:29,397
WAVES FROM THE CORTEX ITSELF IS

795
00:25:29,397 --> 00:25:31,265
JUST DEVELOPING SO THIS IS

796
00:25:31,265 --> 00:25:32,133
REALLY PROPAGATING UP THROUGH

797
00:25:32,133 --> 00:25:33,434
THE VISUAL SYSTEM BEFORE THE

798
00:25:33,434 --> 00:25:35,069
ANIMAL CAN SEE.

799
00:25:35,069 --> 00:25:36,070
SO ONE OF THE FEATURES AND

800
00:25:36,070 --> 00:25:37,438
SOMETHING I'D LIKE TO EMPHASIZE

801
00:25:37,438 --> 00:25:38,672
THAT MAKES ALL OF THIS POSSIBLE

802
00:25:38,672 --> 00:25:41,642
EARLY IN DEVELOPMENT IS THE FACT

803
00:25:41,642 --> 00:25:42,843
THAT WE DON'T THINK OF -- SO AS

804
00:25:42,843 --> 00:25:44,478
I SAID, THESE SEEM TO BE

805
00:25:44,478 --> 00:25:45,579
MEDIATED BY SYNAPSES, AND FOR

806
00:25:45,579 --> 00:25:47,014
THOSE OF US WHO STUDY THE

807
00:25:47,014 --> 00:25:48,115
NERVOUS SYSTEM, WE LIKE TO THINK

808
00:25:48,115 --> 00:25:51,152
OF SYNAPSES AS BEING KIND OF

809
00:25:51,152 --> 00:25:52,820
POINT-TO-POINT CONNECTORS,

810
00:25:52,820 --> 00:25:54,755
NEURON A ACTIVATES NEURON B BUT

811
00:25:54,755 --> 00:25:56,524
NOT NEURON C OR D SO WE REALLY

812
00:25:56,524 --> 00:25:58,492
WANT TO HAVE THIS VERY PRECISE

813
00:25:58,492 --> 00:25:58,826
WIRING.

814
00:25:58,826 --> 00:26:00,060
TURNS OUT ONE OF THE FEATURES

815
00:26:00,060 --> 00:26:01,862
THAT'S CRITICAL FOR PROPAGATING

816
00:26:01,862 --> 00:26:03,464
RETINAL WAVES IS THAT EARLY IN

817
00:26:03,464 --> 00:26:04,131
DEVELOPMENT, NEUROTRANSMITTERS

818
00:26:04,131 --> 00:26:05,299
SEEM TO BE RELEASE IN THIS VERY

819
00:26:05,299 --> 00:26:05,733
DIFFUSE WAY.

820
00:26:05,733 --> 00:26:07,902
SO YOU HAVE THIS KIND OF BEFORE

821
00:26:07,902 --> 00:26:09,103
SYNAPSES HAVE MATURED, YOU HAVE

822
00:26:09,103 --> 00:26:10,871
CELLS THAT ARE RELEASING

823
00:26:10,871 --> 00:26:11,639
NEUROTRANSMITTER BUT THEY'RE

824
00:26:11,639 --> 00:26:13,374
RELEASING THEM IN CLOUDS.

825
00:26:13,374 --> 00:26:15,309
SO THIS IS TRUE FOR BOTH STAGE

826
00:26:15,309 --> 00:26:16,977
TWO AND STAGE III WAVES WHERE

827
00:26:16,977 --> 00:26:18,078
THERE'S THIS DIFFUSE RELEASE,

828
00:26:18,078 --> 00:26:19,280
AND I JUST WANT TO SHOW YOU THE

829
00:26:19,280 --> 00:26:20,915
KINDS OF EXPERIMENTS WE'VE DONE

830
00:26:20,915 --> 00:26:22,883
TO DEMONSTRATE THIS VOLUMETRIC

831
00:26:22,883 --> 00:26:24,218
RELEASE OF NEUROTRANSMITTER.

832
00:26:24,218 --> 00:26:26,187
SO ONE OF THEM WERE EXPERIMENTS

833
00:26:26,187 --> 00:26:28,589
CARRIED OUT BY KEVIN FORD WHO

834
00:26:28,589 --> 00:26:30,658
USED A REALLY AMAZING -- WHAT'S

835
00:26:30,658 --> 00:26:34,295
CALLED CELL-BASED SENSOR.

836
00:26:34,295 --> 00:26:41,035
THIS IS A HEX CELL EXPRESSING A

837
00:26:41,035 --> 00:26:41,936
MUSCARINIC ACETYLCHOLINE

838
00:26:41,936 --> 00:26:43,237
RECEPTOR, COUPLED TO RELEASING

839
00:26:43,237 --> 00:26:44,338
CALCIUM FROM STORES.

840
00:26:44,338 --> 00:26:48,275
THIS HEX CELL IS ALSO EXPRESSING

841
00:26:48,275 --> 00:26:51,445
A CALCIUM SENSOR AND THE IDEA IS

842
00:26:51,445 --> 00:26:52,980
WHEN ACETYLCHOLINE BINDS TO THIS

843
00:26:52,980 --> 00:26:54,715
G PROTEIN COUPLED RECEPTOR YOU

844
00:26:54,715 --> 00:26:56,016
GET A RELEASE FROM STORES AND

845
00:26:56,016 --> 00:26:57,151
YOU'LL SEE A SIGNATURE IN THE

846
00:26:57,151 --> 00:26:57,451
CALCIUM.

847
00:26:57,451 --> 00:26:59,653
SO THIS IS A HEX CELL, SO HOW

848
00:26:59,653 --> 00:27:00,955
ARE WE GOING TO USE THIS TO

849
00:27:00,955 --> 00:27:01,789
RECORD ANYTHING IN RELATION TO

850
00:27:01,789 --> 00:27:02,690
THE RETINA?

851
00:27:02,690 --> 00:27:05,059
WHAT KEVIN DID IS HE LITERALLY

852
00:27:05,059 --> 00:27:06,660
THREW IT ON THE SURFACE OF THE

853
00:27:06,660 --> 00:27:08,062
RETINA WHILE HE'S DOING

854
00:27:08,062 --> 00:27:09,597
RECORDING FROM A GANGLION CELL.

855
00:27:09,597 --> 00:27:12,666
SO HERE ARE EXAMPLES OF HEX

856
00:27:12,666 --> 00:27:13,534
CELLS EXPRESSING THESE

857
00:27:13,534 --> 00:27:14,201
INDICATORS.

858
00:27:14,201 --> 00:27:15,603
WHAT KEVIN FOUND IS THAT EVERY

859
00:27:15,603 --> 00:27:17,471
TIME YOU COULD USE THIS VOLTAGE

860
00:27:17,471 --> 00:27:19,874
CLAMP RECORDING TO SAY I KNOW

861
00:27:19,874 --> 00:27:20,774
ACETYLCHOLINE IS BEING RELEASED

862
00:27:20,774 --> 00:27:21,942
AT THIS STAGE BECAUSE WE CAN SEE

863
00:27:21,942 --> 00:27:23,143
THE SYNAPTIC CURRENTS, HE SAW

864
00:27:23,143 --> 00:27:28,315
THIS VERY RELIABLE CLOUD OF

865
00:27:28,315 --> 00:27:29,817
ACETYLCHOLINE NOT ONLY DIFFUSING

866
00:27:29,817 --> 00:27:32,152
THROUGH THE SURFACE OF THE

867
00:27:32,152 --> 00:27:34,755
RETINA, TO THE HEX CELL SITTING

868
00:27:34,755 --> 00:27:35,189
MICRONS AWAY.

869
00:27:35,189 --> 00:27:37,057
SO THIS IS REALLY EVIDENCE THAT

870
00:27:37,057 --> 00:27:37,825
ACETYLCHOLINE IS BEING RELEASED

871
00:27:37,825 --> 00:27:40,227
IN A CLOUD.

872
00:27:40,227 --> 00:27:42,530
WE'VE ALSO USED SOME GENETICALLY

873
00:27:42,530 --> 00:27:43,163
ENCODED INDICATORS.

874
00:27:43,163 --> 00:27:45,032
THIS IS AN EXAMPLE OF SOMETHING

875
00:27:45,032 --> 00:27:46,467
CALLED GLUE SNIFFER, GREAT NAME,

876
00:27:46,467 --> 00:27:48,435
IT'S A WAY OF DETECTING DIFFUSE

877
00:27:48,435 --> 00:27:49,203
RELEASE OF GLUTAMATE.

878
00:27:49,203 --> 00:27:50,504
WE COULD EXPRESS THAT IN THE

879
00:27:50,504 --> 00:27:54,975
RETINA AND YOU CAN SEE DURING

880
00:27:54,975 --> 00:27:55,976
STAGE 3 WAVES, THIS IS GOING TO

881
00:27:55,976 --> 00:27:57,378
BE GLUTAMATE THAT'S NOT CONFINED

882
00:27:57,378 --> 00:27:59,580
TO SYNAPSES, BUT IT'S JUST

883
00:27:59,580 --> 00:28:00,915
GETTING RELEASED IN CLOUDS

884
00:28:00,915 --> 00:28:04,385
DURING THIS TIME.

885
00:28:04,385 --> 00:28:05,486
THIS IS GOING TO BE VERY

886
00:28:05,486 --> 00:28:06,820
IMPORTANT WHEN I TALK LATER

887
00:28:06,820 --> 00:28:07,688
ABOUT SOME CURRENT WORK IN THE

888
00:28:07,688 --> 00:28:09,990
LAB, IF I GET TO IT, ABOUT

889
00:28:09,990 --> 00:28:11,725
MATURATION OF SAY THE

890
00:28:11,725 --> 00:28:12,826
VASCULATURE BECAUSE NOW YOU HAVE

891
00:28:12,826 --> 00:28:14,328
THIS CLOUD OF NEUROTRANSMITTER

892
00:28:14,328 --> 00:28:15,329
THAT'S BEING RELEASED AND

893
00:28:15,329 --> 00:28:16,864
THERE'S A LOT OF DEVELOPMENT OF

894
00:28:16,864 --> 00:28:18,165
OTHER CELL TYPES IN THE RETINA

895
00:28:18,165 --> 00:28:19,934
THAT MIGHT BE INFLUENCED BY

896
00:28:19,934 --> 00:28:22,236
RELEASE OF NEUROTRANSMITTERS.

897
00:28:22,236 --> 00:28:24,638
SO THIS DIFFUSE RELEASE GOES

898
00:28:24,638 --> 00:28:26,607
AWAY AS THE ANIMALS MATURE, SO

899
00:28:26,607 --> 00:28:27,474
IT'S DEFINITELY A FEATURE OF

900
00:28:27,474 --> 00:28:30,210
SOMETHING THAT JUST HAPPENS

901
00:28:30,210 --> 00:28:35,015
DURING RETINAL WAVES.

902
00:28:35,015 --> 00:28:36,884
SO THAT GIVES YOU A KIND OF A

903
00:28:36,884 --> 00:28:37,751
FEEL OF EXPERIMENTS WE DO IN THE

904
00:28:37,751 --> 00:28:38,285
LAB.

905
00:28:38,285 --> 00:28:39,286
WE WANT TO UNDERSTAND THE

906
00:28:39,286 --> 00:28:40,387
CIRCUIT BASIS OF HOW THESE WAVES

907
00:28:40,387 --> 00:28:41,789
ARE GENERATED BUT FOR ANYONE TO

908
00:28:41,789 --> 00:28:43,123
CARE ABOUT THIS, WE HAVE TO SHOW

909
00:28:43,123 --> 00:28:46,393
THERE'S A ROLE THEY PLAY, A ROLE

910
00:28:46,393 --> 00:28:47,595
FOR THESE WAVES IN DEVELOPMENT.

911
00:28:47,595 --> 00:28:50,965
SO TO GET -- SO WHAT'S GOING ON

912
00:28:50,965 --> 00:28:54,068
DURING DEVELOPMENT?

913
00:28:54,068 --> 00:28:56,236
WELL, IF DURING THE FIRST

914
00:28:56,236 --> 00:28:57,004
POSTNATAL WEEK IS WHEN THE

915
00:28:57,004 --> 00:28:58,339
RETINA IS MAKING ITS CONNECTIONS

916
00:28:58,339 --> 00:28:59,773
TO THE BRAIN, AND WHEN THE

917
00:28:59,773 --> 00:29:01,175
RETINA MAKES ITS CONNECTIONS TO

918
00:29:01,175 --> 00:29:06,313
THE BRAIN, RETINAL GANGLION CELL

919
00:29:06,313 --> 00:29:12,753
AXONS ASH RISE AN ARBORIZE AND A

920
00:29:12,753 --> 00:29:13,754
VARIETY OF REFINEMENTS.

921
00:29:13,754 --> 00:29:15,623
THE WAY THAT WE WANTED TO SEE IF

922
00:29:15,623 --> 00:29:18,025
RETINAL WAVES WERE INVOLVED IN

923
00:29:18,025 --> 00:29:20,327
THIS DEVELOPMENTAL PROCESS IS WE

924
00:29:20,327 --> 00:29:22,262
TOOK ADVANTAGE OF KNOWING THAT

925
00:29:22,262 --> 00:29:24,598
THIS WAS A CIRCUIT MEDIATED BY

926
00:29:24,598 --> 00:29:25,366
ACETYLCHOLINE SO WE MADE MICE

927
00:29:25,366 --> 00:29:27,334
THAT WERE LACKING THE BETA

928
00:29:27,334 --> 00:29:32,906
2 SUBUNIT OF THE AN ANY COTINGE

929
00:29:32,906 --> 00:29:34,008
ACETYLCHOLINE RECEPTORS AND WERE

930
00:29:34,008 --> 00:29:36,510
ABLE TO SHOW THIS MOUSE HAD

931
00:29:36,510 --> 00:29:39,013
REDUCED RETINAL WAVES AND WOULD

932
00:29:39,013 --> 00:29:41,782
BE A GOOD MODEL CY SYSTEM.

933
00:29:41,782 --> 00:29:43,584
THIS IS A MULTIELECTRODE ARRAY

934
00:29:43,584 --> 00:29:44,618
RECORDING FROM A WILD TYPE

935
00:29:44,618 --> 00:29:45,085
MOUSE.

936
00:29:45,085 --> 00:29:46,387
I JUST LOVE TO SHOW THIS TO SHOW

937
00:29:46,387 --> 00:29:48,022
YOU WHAT THE PATTERN IS.

938
00:29:48,022 --> 00:29:49,890
WHAT'S ALONG THE Y AXIS IS A

939
00:29:49,890 --> 00:29:51,191
DIFFERENT GANGLION CELL, ALONG

940
00:29:51,191 --> 00:29:52,726
THE X AXIS IS TIME AND YOU CAN

941
00:29:52,726 --> 00:29:53,961
SEE WHEN A WAVE COMES THROUGH,

942
00:29:53,961 --> 00:29:55,562
YOU GET A BURST OF ACTION

943
00:29:55,562 --> 00:29:56,563
POTENTIALS AND THEN NOTHING.

944
00:29:56,563 --> 00:29:58,298
THEN A BURST OF ACTION

945
00:29:58,298 --> 00:29:59,500
POTENTIALS THAT PROPAGATE ACROSS

946
00:29:59,500 --> 00:30:02,536
AND THEN NOTHING.

947
00:30:02,536 --> 00:30:05,272
IN THE BETA 2 KNOCKOUT, WAVES

948
00:30:05,272 --> 00:30:06,106
ARE MUCH LESS FREQUENT.

949
00:30:06,106 --> 00:30:07,841
YOU CAN'T SEE IT IN THIS TIME

950
00:30:07,841 --> 00:30:09,843
SCALE BUT INSTEAD OF IT BEING A

951
00:30:09,843 --> 00:30:10,577
PROPAGATING WAVE, THEY HAD

952
00:30:10,577 --> 00:30:11,345
FLASHES.

953
00:30:11,345 --> 00:30:14,515
SO THEY PROPAGATED SUPER FAST

954
00:30:14,515 --> 00:30:17,051
AND MOSTLY THE RETINA WAS

955
00:30:17,051 --> 00:30:20,354
SILENT.

956
00:30:20,354 --> 00:30:22,356
SO WHAT HAPPENS TO THE RETINAL

957
00:30:22,356 --> 00:30:23,424
PROJECTIONS IN THE BRAIN IN THIS

958
00:30:23,424 --> 00:30:23,991
MODEL OF MICE?

959
00:30:23,991 --> 00:30:25,059
THE FIRST SET OF EXPERIMENTS WE

960
00:30:25,059 --> 00:30:30,297
DID IS WE LOOKED AT THE

961
00:30:30,297 --> 00:30:30,998
RETINOTOPIC PROJECTION FROM THE

962
00:30:30,998 --> 00:30:32,332
RETINA TO THE SUPERIOR

963
00:30:32,332 --> 00:30:32,866
COLLICULUS.

964
00:30:32,866 --> 00:30:34,268
SO THE WAY WE WOULD LOOK AT THIS

965
00:30:34,268 --> 00:30:37,137
IS THESE WERE IN LAB RANGE OF

966
00:30:37,137 --> 00:30:39,206
MOTION WITH TODD MCLAUGHLIN

967
00:30:39,206 --> 00:30:42,276
WHILE A POSTDOC IN DENNIS

968
00:30:42,276 --> 00:30:43,243
O'LEARY'S LAB AT THE SALK

969
00:30:43,243 --> 00:30:43,811
INSTITUTE.

970
00:30:43,811 --> 00:30:45,779
SO WE PUT A LITTLE CRYSTAL OF A

971
00:30:45,779 --> 00:30:48,615
FLUORESCENT DYE IN THE RETINA SO

972
00:30:48,615 --> 00:30:50,184
A FEW GANGLION CELLS WOULD TAKE

973
00:30:50,184 --> 00:30:51,985
UP THIS CRYSTAL AND IT WOULD

974
00:30:51,985 --> 00:30:53,787
DIFFUSE DOWN THEIR AXONS, AND

975
00:30:53,787 --> 00:30:55,856
YOU COULD SEE WHERE THOSE AXONS

976
00:30:55,856 --> 00:30:56,857
PROJECT IN THE SUPERIOR

977
00:30:56,857 --> 00:30:58,492
COLLICULUS.

978
00:30:58,492 --> 00:31:01,562
AND SO WHEN YOU DO THAT, SO WHAT

979
00:31:01,562 --> 00:31:02,663
YOU'RE LOOKING AT HERE IS AN

980
00:31:02,663 --> 00:31:04,198
IMAGE OF THE SUPERIOR COLLICULUS

981
00:31:04,198 --> 00:31:05,833
AFTER WE'VE PUT THIS CRYSTAL IN,

982
00:31:05,833 --> 00:31:07,267
WE WAIT 24 HOURS, WE CAN DISSECT

983
00:31:07,267 --> 00:31:09,670
OUT THE COLLICULUS AND SEE THESE

984
00:31:09,670 --> 00:31:11,238
FEW GANGLION CELLS PROJECT TO A

985
00:31:11,238 --> 00:31:12,840
VERY SMALL REGION IN THE

986
00:31:12,840 --> 00:31:14,041
COLLICULUS AND THIS IS THE BASIS

987
00:31:14,041 --> 00:31:15,275
OF THE RETINOTOPIC MAP.

988
00:31:15,275 --> 00:31:17,444
SO AS YOU MOVE ACROSS THE RETINA

989
00:31:17,444 --> 00:31:18,679
AT DIFFERENT LOCATIONS, YOU MOVE

990
00:31:18,679 --> 00:31:20,214
ACROSS THE COLLICULUS IN A VERY

991
00:31:20,214 --> 00:31:21,615
SMOOTH MAPPING.

992
00:31:21,615 --> 00:31:23,117
YOU DO THAT SAME EXPERIMENT,

993
00:31:23,117 --> 00:31:25,753
THIS IS POSTNATAL DAY 8, JUST

994
00:31:25,753 --> 00:31:27,421
ONE WEEK EARLIER, AND YOU SEE

995
00:31:27,421 --> 00:31:29,289
THAT THOSE RETINAL GANGLION

996
00:31:29,289 --> 00:31:30,824
CELLS, THAT SMALL CLUSTER OF

997
00:31:30,824 --> 00:31:32,126
RETINAL GANGLION CELLS PROJECT

998
00:31:32,126 --> 00:31:33,093
ALL OVER THE COLLICULUS, AND

999
00:31:33,093 --> 00:31:35,195
THEN THIS FIRST POSTNATAL WEEK

1000
00:31:35,195 --> 00:31:37,531
REPRESENTS THIS PERIOD OF

1001
00:31:37,531 --> 00:31:39,700
REFINEMENT, SO THIS NOW BEFORE

1002
00:31:39,700 --> 00:31:41,335
VISION, THIS IS WHEN THERE ARE

1003
00:31:41,335 --> 00:31:42,569
RETINAL WAVES, SO WE LOOK TO SEE

1004
00:31:42,569 --> 00:31:45,739
WHAT HAPPENS TO THIS REFINEMENT

1005
00:31:45,739 --> 00:31:47,141
PROCESS IN THE BETA 2 KNOCKOUT.

1006
00:31:47,141 --> 00:31:48,809
THESE ARE TWO EXAMPLES OF WHAT

1007
00:31:48,809 --> 00:31:49,676
WE SAW ON THE RIGHT.

1008
00:31:49,676 --> 00:31:51,879
SO NORMALLY AT POSTNATAL DAY 8,

1009
00:31:51,879 --> 00:31:53,313
WE HAVE THIS NICE -- WE CALL

1010
00:31:53,313 --> 00:31:54,815
THEM TERMINATION ZONES, WE HAVE

1011
00:31:54,815 --> 00:31:56,150
THIS NICE NARROW PROJECTION

1012
00:31:56,150 --> 00:31:57,117
PATTERN BUT IN THE MOUSE THAT

1013
00:31:57,117 --> 00:31:58,552
DEPARTMENT HAVE WAVES OR HAD

1014
00:31:58,552 --> 00:31:59,787
REDUCED WAVES AT THAT TIME, YOU

1015
00:31:59,787 --> 00:32:01,188
GET SOME REFINEMENT BUT NOT

1016
00:32:01,188 --> 00:32:02,956
NEARLY AS MUCH REFINEMENT AS YOU

1017
00:32:02,956 --> 00:32:08,428
WOULD GET IN A WILD TYPE.

1018
00:32:08,428 --> 00:32:10,397
THIS SORT OF RETINAL GANGLION

1019
00:32:10,397 --> 00:32:13,033
CELLS PROJECTING BROADLY MEANT

1020
00:32:13,033 --> 00:32:14,334
THEY HAD BLURRY VISION AND THAT

1021
00:32:14,334 --> 00:32:15,669
WAS ONE OF THE THINGS THEY FOUND

1022
00:32:15,669 --> 00:32:16,436
FOR THESE MICE.

1023
00:32:16,436 --> 00:32:17,938
SO WE THINK RETINAL WAVES ARE

1024
00:32:17,938 --> 00:32:19,273
IMPORTANT FOR DRIVING THIS

1025
00:32:19,273 --> 00:32:20,507
RETINOTOPIC REFINEMENT AND EVEN

1026
00:32:20,507 --> 00:32:22,242
WHEN THIS MOUSE OPENS ITS EYES

1027
00:32:22,242 --> 00:32:23,177
AND HAS VISION, THEY GET A

1028
00:32:23,177 --> 00:32:25,212
LITTLE BIT OF REFINEMENT BUT IT

1029
00:32:25,212 --> 00:32:26,413
DOESN'T MAKE UP FOR WHAT THEY

1030
00:32:26,413 --> 00:32:28,415
LACKED WHEN THEY DIDN'T HAVE

1031
00:32:28,415 --> 00:32:28,982
RETINAL WAVES.

1032
00:32:28,982 --> 00:32:31,952
SO WAVES ARE IMPORTANT FOR

1033
00:32:31,952 --> 00:32:33,487
SETTING UP THIS SMOOTH

1034
00:32:33,487 --> 00:32:34,488
RETINOTOPIC MAP, THAT'S

1035
00:32:34,488 --> 00:32:37,958
IMPORTANT FOR SHARP VISION.

1036
00:32:37,958 --> 00:32:40,060
OH, AND ANOTHER THING THAT

1037
00:32:40,060 --> 00:32:41,195
PEOPLE MAY HAVE HEARD ABOUT IS

1038
00:32:41,195 --> 00:32:44,097
THAT THERE'S A FEATURE IN VISUAL

1039
00:32:44,097 --> 00:32:50,037
SYSTEMS CALLED OCULAR DOM NABS E

1040
00:32:50,037 --> 00:32:52,206
COLUMNS, SO OCULAR DOMINANCE

1041
00:32:52,206 --> 00:32:56,176
COLUMNS EMERGE FROM -- FIRST IN

1042
00:32:56,176 --> 00:32:57,010
EYE-SPECIFIC SEGREGATION THAT

1043
00:32:57,010 --> 00:32:58,011
HAPPENS IN THE THALAMUS.

1044
00:32:58,011 --> 00:32:58,912
SO THE WAY WE LOOK AT THIS IS

1045
00:32:58,912 --> 00:33:01,215
THE FOLLOWING, AS WE PUT ONE

1046
00:33:01,215 --> 00:33:03,517
COLOR DYE IN ONE EYE AND IT GETS

1047
00:33:03,517 --> 00:33:06,920
SEPTEMBER SENT DOWN THE AXONS O,

1048
00:33:06,920 --> 00:33:07,988
THEN YOU HAVE A DIFFERENT COLOR

1049
00:33:07,988 --> 00:33:09,356
IN THE OTHER EYE, AND YOU'LL

1050
00:33:09,356 --> 00:33:10,557
FIND THAT WHEN YOU LOOK IN THE

1051
00:33:10,557 --> 00:33:12,192
THALAMUS, THAT THERE IS THIS

1052
00:33:12,192 --> 00:33:13,193
SEGREGATION FROM THE LEFT EYE TO

1053
00:33:13,193 --> 00:33:14,928
THE RIGHT EYE, AND IT'S THOSE

1054
00:33:14,928 --> 00:33:17,030
NEURONS WITHIN THOSE TWO PARTS

1055
00:33:17,030 --> 00:33:18,699
OF THE LGN THAT WILL GO UP AND

1056
00:33:18,699 --> 00:33:22,402
FORM THE OCULAR DOMINANCE

1057
00:33:22,402 --> 00:33:22,936
COLUMNS.

1058
00:33:22,936 --> 00:33:26,240
THESE WERE DONE BY ALEX TIRIAC.

1059
00:33:26,240 --> 00:33:29,243
ALEX JUST STARTED HIS OWN LAB AT

1060
00:33:29,243 --> 00:33:29,977
VANDERBILT UNIVERSITY.

1061
00:33:29,977 --> 00:33:31,178
WHAT ALEX DID FOR THESE

1062
00:33:31,178 --> 00:33:32,512
EXPERIMENTS WAS HE WOULD DO

1063
00:33:32,512 --> 00:33:34,147
THESE INJECTIONS, HE'D WAIT 24

1064
00:33:34,147 --> 00:33:35,682
HOURS FOR THIS TRANSPORT TO

1065
00:33:35,682 --> 00:33:37,084
HAPPEN, AND THEN HE WOULD USE

1066
00:33:37,084 --> 00:33:39,286
THIS METHOD CALLED CUBIC THAT

1067
00:33:39,286 --> 00:33:41,054
ALLOWED YOU TO CLEAR THE WHOLE

1068
00:33:41,054 --> 00:33:42,256
BRAIN, AND THEN HE COULD LOOK AT

1069
00:33:42,256 --> 00:33:43,790
THE RETINAL PROJECTIONS

1070
00:33:43,790 --> 00:33:45,325
EVERYWHERE IN THE BRAIN, BOTH IN

1071
00:33:45,325 --> 00:33:46,860
A WILD TYPE AND IN KNOCKOUT.

1072
00:33:46,860 --> 00:33:48,295
SO WHEN YOU DO THAT, WHILE

1073
00:33:48,295 --> 00:33:53,634
LOOKING THROUGH THE LATERAL

1074
00:33:53,634 --> 00:33:55,736
NUCLEUS YOU SEE A STRON

1075
00:33:55,736 --> 00:33:56,703
CONTRALATERAL PROJECTION, NOW

1076
00:33:56,703 --> 00:33:57,504
WE'RE SORT OF TRAVELING THROUGH

1077
00:33:57,504 --> 00:33:59,473
THE THALAMUS, THE VISUAL

1078
00:33:59,473 --> 00:34:02,109
THALAMUS, AND YOU CAN SEE

1079
00:34:02,109 --> 00:34:03,410
THERE'S AN IPSILATERAL

1080
00:34:03,410 --> 00:34:05,178
PROJECTION THAT'S SEGREGATED SO

1081
00:34:05,178 --> 00:34:12,152
IN WILD TYPE DOMINATED BY

1082
00:34:12,152 --> 00:34:16,423
CONTRALATERAL PRO JEX, AND THATY

1083
00:34:16,423 --> 00:34:17,758
START INITIALLY BY OVERLAPPING

1084
00:34:17,758 --> 00:34:19,192
AND THE SEGREGATION OCCURS

1085
00:34:19,192 --> 00:34:20,661
DURING THE FIRST POSTNATAL WEEK

1086
00:34:20,661 --> 00:34:22,262
AND IN THE MICE THAT ARE LACKING

1087
00:34:22,262 --> 00:34:23,897
RETINAL WAVES, WE SEE VERY

1088
00:34:23,897 --> 00:34:24,564
LITTLE SEGREGATION.

1089
00:34:24,564 --> 00:34:26,767
IT STAYS FROZEN IN THE IMMATURE

1090
00:34:26,767 --> 00:34:29,403
PATTERN WHERE THE CONTRAIS NOT

1091
00:34:29,403 --> 00:34:31,305
DRIVEN OUT WHERE THE I PSI

1092
00:34:31,305 --> 00:34:34,007
PROJECTION IS AND THE IPSI

1093
00:34:34,007 --> 00:34:34,908
PROJECTION IS A LITTLE BIT

1094
00:34:34,908 --> 00:34:35,442
BROADER.

1095
00:34:35,442 --> 00:34:36,777
SO FROM THIS WE KNOW RETINAL

1096
00:34:36,777 --> 00:34:37,878
WAVES ARE IMPORTANT FOR DRIVING

1097
00:34:37,878 --> 00:34:39,513
THIS EYE-SPECIFIC SEGREGATION

1098
00:34:39,513 --> 00:34:41,415
AND INDEED THESE MICE WHEN THEY

1099
00:34:41,415 --> 00:34:44,685
GROW UP HAVE DEFICITS IN

1100
00:34:44,685 --> 00:34:47,087
BINOCULAR VISION, KIND OF WEAK

1101
00:34:47,087 --> 00:34:48,722
IN MICE TO BEGIN WITH BUT THEY

1102
00:34:48,722 --> 00:34:50,490
DO HAVE DEPTH PERCEPTION AND

1103
00:34:50,490 --> 00:34:52,993
IT'S IMPAIRED IN THESE MICE,

1104
00:34:52,993 --> 00:34:53,894
SOMETHING IMPORTANT FOR SETTING

1105
00:34:53,894 --> 00:34:55,329
UP THEREBY KNOCK LAR CIRCUITS.

1106
00:34:55,329 --> 00:34:58,932
OKAY.

1107
00:34:58,932 --> 00:35:00,801
SO ANOTHER THING HAPPENING

1108
00:35:00,801 --> 00:35:02,035
DURING THIS SECOND POSTNATAL

1109
00:35:02,035 --> 00:35:03,203
WEEK ARE THE CIRCUITS IN THE

1110
00:35:03,203 --> 00:35:04,438
RETINA THEMSELVES ARE GETTING

1111
00:35:04,438 --> 00:35:06,606
WIRED UP SO WE HAVE MORE

1112
00:35:06,606 --> 00:35:07,808
RECENTLY BEEN LOOKING TO SEE

1113
00:35:07,808 --> 00:35:08,809
WHETHER OR NOT RETINAL WAVES ARE

1114
00:35:08,809 --> 00:35:09,810
IMPORTANT FOR SETTING UP THE

1115
00:35:09,810 --> 00:35:11,011
CIRCUITS WITHIN THE RETINA.

1116
00:35:11,011 --> 00:35:13,146
THIS IS WHAT WAS REFERRED TO IN

1117
00:35:13,146 --> 00:35:16,783
THE INTRODUCTION.

1118
00:35:16,783 --> 00:35:18,318
SO THESE ARE RECENT EXPERIMENTS

1119
00:35:18,318 --> 00:35:23,857
LED BY ALEX TIRIAC AND TWO

1120
00:35:23,857 --> 00:35:25,025
GRADUATE STUDENTS, AND I'LL TALK

1121
00:35:25,025 --> 00:35:26,994
ABOUT THEIR WORK ABOUT HOW

1122
00:35:26,994 --> 00:35:28,095
RETINAL WAVES ARE IMPORTANT FOR

1123
00:35:28,095 --> 00:35:29,196
SENDING UP A PARTICULAR CIRCUIT

1124
00:35:29,196 --> 00:35:30,497
IN THE RETINA AND THIS WAS

1125
00:35:30,497 --> 00:35:36,837
PUBLISHED LAST YEAR.

1126
00:35:36,837 --> 00:35:38,605
SO WITHOUT GOING INTO TOO MANY

1127
00:35:38,605 --> 00:35:40,040
DETAILS BECAUSE IT WAS SO NICELY

1128
00:35:40,040 --> 00:35:40,907
INTRODUCED, THERE ARE CELLS IN

1129
00:35:40,907 --> 00:35:43,443
YOUR RETINA THAT ARE VERY

1130
00:35:43,443 --> 00:35:45,846
SENSITIVE TO THE DIRECTION THAT

1131
00:35:45,846 --> 00:35:46,713
SOMETHING MOVES IN THE VISUAL

1132
00:35:46,713 --> 00:35:48,048
WORLD AND I WANT TO SAY THESE

1133
00:35:48,048 --> 00:35:49,249
ARE VERY IMPORTANT BECAUSE THESE

1134
00:35:49,249 --> 00:35:51,251
ARE THE CELLS THAT ARE CALLED

1135
00:35:51,251 --> 00:35:52,019
DIRECTION-SELECTIVE GANGLION

1136
00:35:52,019 --> 00:35:53,320
CELLS, AND THESE CELLS ARE VERY

1137
00:35:53,320 --> 00:35:57,691
IMPORTANT FOR MICE WHEN MICE

1138
00:35:57,691 --> 00:35:58,792
MOVE THROUGH THE WORLD, THEY

1139
00:35:58,792 --> 00:36:00,027
HAVE OPTIC FLOW THAT GOES ACROSS

1140
00:36:00,027 --> 00:36:01,895
THE RETINAS, THEY HAVE

1141
00:36:01,895 --> 00:36:03,530
COMPENSATORY EYE MOVEMENTS THAT

1142
00:36:03,530 --> 00:36:06,366
ARE MEDIATED -- IT'S A REFLEXIVE

1143
00:36:06,366 --> 00:36:08,368
EYE MOVEMENT WHICH IS THEIR WAY

1144
00:36:08,368 --> 00:36:10,137
OF STABILIZING IMAGES, SO THEY

1145
00:36:10,137 --> 00:36:11,671
DON'T HAVE THE SAME SORT OF

1146
00:36:11,671 --> 00:36:12,672
MICRO -- THEY DON'T HAVE THE

1147
00:36:12,672 --> 00:36:18,145
SAME SORT OF MICRO SACCADIC

1148
00:36:18,145 --> 00:36:19,546
STRATEGIES THAT PRIMATES HAVE

1149
00:36:19,546 --> 00:36:21,748
BUT THEY HAVE THIS REFLEXIVE EYE

1150
00:36:21,748 --> 00:36:22,549
MOVEMENT THAT'S VERY IMPORTANT

1151
00:36:22,549 --> 00:36:22,983
FOR THAT.

1152
00:36:22,983 --> 00:36:25,485
SO THERE ARE FOUR TYPES OF THESE

1153
00:36:25,485 --> 00:36:28,355
DIRECTION SELECTIVE GANGLION

1154
00:36:28,355 --> 00:36:28,555
CELLS.

1155
00:36:28,555 --> 00:36:30,223
THERE ARE THE ONES THAT PREFER

1156
00:36:30,223 --> 00:36:32,359
LEFT, RIGHT, UP AND DOWN, AND

1157
00:36:32,359 --> 00:36:35,262
ONE OF THE THINGS THAT WE FOUND

1158
00:36:35,262 --> 00:36:36,129
VERY SURPRISING WAS THAT IN A

1159
00:36:36,129 --> 00:36:37,464
MOUSE THAT DOESN'T HAVE RETINAL

1160
00:36:37,464 --> 00:36:40,867
WAVES, THEY STILL HAVE AN UP

1161
00:36:40,867 --> 00:36:41,701
PREFERENCE, A DOWN PREFERENCE

1162
00:36:41,701 --> 00:36:43,170
BUT THEY NOW HAVE NO CELLS THAT

1163
00:36:43,170 --> 00:36:44,071
PREFER LEFT OR RIGHT.

1164
00:36:44,071 --> 00:36:45,372
AND THAT MEANS THAT THESE MICE

1165
00:36:45,372 --> 00:36:49,543
ACTUALLY DON'T HAVE A HORIZONTAL

1166
00:36:49,543 --> 00:36:51,078
OPTOKINETIC REFLEX BUT A

1167
00:36:51,078 --> 00:36:52,512
PERFECTLY NORMAL VERTICAL

1168
00:36:52,512 --> 00:36:53,180
OPTOKINETIC REFLEX.

1169
00:36:53,180 --> 00:36:56,817
TOTAL TOTALLY BIZARRE AND A BIG

1170
00:36:56,817 --> 00:36:58,018
QUESTION THE LAB IS TRYING TO

1171
00:36:58,018 --> 00:36:58,985
UNDERSTAND BUT WE KNOW WAVES ARE

1172
00:36:58,985 --> 00:37:01,521
IMPORTANT FOR SETTING UP THIS

1173
00:37:01,521 --> 00:37:02,289
REFLEX.

1174
00:37:02,289 --> 00:37:04,891
WE HAVE A HYPOTHESIS OF HOW THIS

1175
00:37:04,891 --> 00:37:06,026
MIGHT BE HAPPENING THAT YOU'LL

1176
00:37:06,026 --> 00:37:06,893
HEAR ABOUT SOON.

1177
00:37:06,893 --> 00:37:07,661
SO WE KNOW WAVES ARE IMPORTANT

1178
00:37:07,661 --> 00:37:08,128
FOR THAT.

1179
00:37:08,128 --> 00:37:09,863
SO WE ALSO WANT TO LOOK AND SEE

1180
00:37:09,863 --> 00:37:11,164
IF WAVES ARE IMPORTANT FOR

1181
00:37:11,164 --> 00:37:12,365
THINGS THAT ARE HAPPENING VERY

1182
00:37:12,365 --> 00:37:14,901
EARLY IN DEVELOPMENT.

1183
00:37:14,901 --> 00:37:19,039
SO WAVES ARE THERE AROUND

1184
00:37:19,039 --> 00:37:22,476
EMBRYONIC DAY 16, AND DURING

1185
00:37:22,476 --> 00:37:23,877
THAT TIME IS WHEN THERE'S A LOT

1186
00:37:23,877 --> 00:37:24,644
OF NEUROGENESIS.

1187
00:37:24,644 --> 00:37:26,179
THE CELLS ARE POSITIONING

1188
00:37:26,179 --> 00:37:27,614
THEMSELVES IN THE GANGLION CELL

1189
00:37:27,614 --> 00:37:29,149
LAYER, AND ACTUALLY THERE'S A

1190
00:37:29,149 --> 00:37:31,885
ROBUST PERIOD OF CELL DEATH THAT

1191
00:37:31,885 --> 00:37:36,356
OCCURS AROUND POSTNATAL DAY TWO,

1192
00:37:36,356 --> 00:37:39,893
AND CHRIS CLANE VOUFO, HER

1193
00:37:39,893 --> 00:37:41,661
THESIS WAS TO LOOK AND SEE IN

1194
00:37:41,661 --> 00:37:43,597
MICE THAT LACKED THESE STAGE I

1195
00:37:43,597 --> 00:37:44,831
WAVES, THESE EARLY WAVES,

1196
00:37:44,831 --> 00:37:46,266
WHETHER OR NOT THESE WERE

1197
00:37:46,266 --> 00:37:48,235
AFFECTED BY A LOSS OF RETINAL

1198
00:37:48,235 --> 00:37:49,536
WAVES AND IT TURNS OUT THEY WERE

1199
00:37:49,536 --> 00:37:50,971
NOT SO RETINAL WAVES DON'T SEEM

1200
00:37:50,971 --> 00:37:54,574
TO BE IMPORTANT FOR DRIVING CELL

1201
00:37:54,574 --> 00:37:55,675
DEATH AS HAS BEEN FOUND IN OTHER

1202
00:37:55,675 --> 00:37:56,910
PARTS OF THE NERVOUS SYSTEM.

1203
00:37:56,910 --> 00:38:00,647
MORE RECENTLY, IN A STUDY WE

1204
00:38:00,647 --> 00:38:01,615
JUST SUBMITTED LAST WEEK, WE

1205
00:38:01,615 --> 00:38:03,583
WANTED TO LOOK AND SEE WHETHER

1206
00:38:03,583 --> 00:38:05,051
RETINAL WAVES WERE IMPORTANT FOR

1207
00:38:05,051 --> 00:38:06,019
THE DIFFERENTIATION OF THE

1208
00:38:06,019 --> 00:38:07,020
DIFFERENT CELL TYPES WITHIN THE

1209
00:38:07,020 --> 00:38:07,454
RETINA.

1210
00:38:07,454 --> 00:38:08,555
I'M GOING TO SAY BECAUSE OF

1211
00:38:08,555 --> 00:38:10,223
TIME, I THINK I'M GOING TO SKIP

1212
00:38:10,223 --> 00:38:13,493
THE DETAILS HERE, BUT I JUST

1213
00:38:13,493 --> 00:38:15,629
WANT TO SORT OF HIGHLIGHT, THESE

1214
00:38:15,629 --> 00:38:17,597
WERE EXPERIMENTS LED BY A

1215
00:38:17,597 --> 00:38:21,535
POSTDOC IN MY LAB, AND MATTHEW

1216
00:38:21,535 --> 00:38:23,069
POE IS A GRADUATE STUDENT AND

1217
00:38:23,069 --> 00:38:25,405
OUR STRATEGY HERE WAS TO USE

1218
00:38:25,405 --> 00:38:28,141
SINGLE CELL RNA SEQUENCING AS A

1219
00:38:28,141 --> 00:38:30,076
WAY OF IDENTIFYING ALL THE

1220
00:38:30,076 --> 00:38:31,178
DIFFERENT GANGLION CELL TYPES

1221
00:38:31,178 --> 00:38:33,280
AND THESE ARE ALL THE DIFFERENT

1222
00:38:33,280 --> 00:38:34,181
GANGLION CELL TYPES THAT HAVE

1223
00:38:34,181 --> 00:38:37,217
BEEN IDENTIFIED IN THE MOUSE

1224
00:38:37,217 --> 00:38:40,787
RETINA, AND WHAT WE COMPARED IS

1225
00:38:40,787 --> 00:38:42,055
WILD TYPE RETINAS WHICH ARE

1226
00:38:42,055 --> 00:38:45,692
SHOWN IN THE BLUE HERE, THE

1227
00:38:45,692 --> 00:38:49,663
GREEN ARE MATURE, THE EXPRESSION

1228
00:38:49,663 --> 00:38:51,932
PROFILES OF MATURE RETINAL

1229
00:38:51,932 --> 00:38:52,933
GANGLION CELLS AND WHAT'S SHOWN

1230
00:38:52,933 --> 00:38:54,467
IN THE RED ARE THE MICE THAT

1231
00:38:54,467 --> 00:38:57,337
LACK BETA 2 -- THAT LACK WAVES

1232
00:38:57,337 --> 00:38:59,973
IN THE FIRST PO POSTNATAL WEEK.

1233
00:38:59,973 --> 00:39:01,541
AS YOU'LL SEE THEE THERE'S LINES

1234
00:39:01,541 --> 00:39:03,109
ALL LOOK PRETTY SIMILAR AS YOU

1235
00:39:03,109 --> 00:39:04,177
LOOK ALONG DIFFERENT CELL TYPES,

1236
00:39:04,177 --> 00:39:06,613
AND WE FOUND NO DRAMATIC IMPACT

1237
00:39:06,613 --> 00:39:10,116
ON THE DIFFERENTIATION OF CELL

1238
00:39:10,116 --> 00:39:13,286
TYPES AT THIS STAGE, IN FACT WE

1239
00:39:13,286 --> 00:39:15,522
LOOKED FOR ANY THINGS REGULATED

1240
00:39:15,522 --> 00:39:16,590
ON THE TRANSCRIPTIONAL LEVEL AND

1241
00:39:16,590 --> 00:39:18,558
WE FOUND VERY, VERY LITTLE.

1242
00:39:18,558 --> 00:39:22,095
SO THERE WERE SOME CELL TYPES OF

1243
00:39:22,095 --> 00:39:22,996
GANGLION CELL TYPES THAT

1244
00:39:22,996 --> 00:39:24,397
ACTUALLY WERE STRONGLY AFFECTED

1245
00:39:24,397 --> 00:39:25,265
BY ACTIVITY, BUT MOST OF THE

1246
00:39:25,265 --> 00:39:27,801
CELL TYPES WERE NOT, AND

1247
00:39:27,801 --> 00:39:29,069
NOTABLY, THOSE DIRECTION

1248
00:39:29,069 --> 00:39:30,103
SELECTIVE GANGLION CELLS WERE

1249
00:39:30,103 --> 00:39:31,771
ONE OF THE CELLS NOT AFFECTED BY

1250
00:39:31,771 --> 00:39:32,305
TRANSCRIPTION.

1251
00:39:32,305 --> 00:39:36,176
SO FROM THIS STUDY -- OR NOT

1252
00:39:36,176 --> 00:39:38,545
AFFECTED AT THIS TRA TRANSCRIPTN

1253
00:39:38,545 --> 00:39:38,778
LEVEL.

1254
00:39:38,778 --> 00:39:39,879
WE THINK WHATEVER WAVES ARE

1255
00:39:39,879 --> 00:39:42,983
DOING TO SET UP THE HORIZONTAL

1256
00:39:42,983 --> 00:39:44,951
DIRECTIONAL SELECTIVITY, IT'S

1257
00:39:44,951 --> 00:39:47,487
EITHER POST TRANSCRIPTIONAL OR

1258
00:39:47,487 --> 00:39:49,055
POTENTIALLY POST TRANSLATIONAL,

1259
00:39:49,055 --> 00:39:50,123
AND HAPPY TO TALK TO PEOPLE

1260
00:39:50,123 --> 00:39:51,224
ABOUT THAT LATER.

1261
00:39:51,224 --> 00:39:54,828
SO I'M GOING TO SKIP THIS.

1262
00:39:54,828 --> 00:39:56,363
SO THIS INTERIM STUDY BEFORE I

1263
00:39:56,363 --> 00:39:57,664
TALK ABOUT THE ONGOING WORK IN

1264
00:39:57,664 --> 00:40:00,433
THE LAB.

1265
00:40:00,433 --> 00:40:02,402
SO RETINAL WAVES ARE A ROBUST

1266
00:40:02,402 --> 00:40:04,804
SOURCE OF ACTIVITY.

1267
00:40:04,804 --> 00:40:05,805
BEFORE VISION AND IS REQUIRED

1268
00:40:05,805 --> 00:40:07,474
FOR THE PRECISE CONNECTIVITY TO

1269
00:40:07,474 --> 00:40:08,908
EMERGE THROUGHOUT THE VISUAL

1270
00:40:08,908 --> 00:40:09,442
SYSTEM.

1271
00:40:09,442 --> 00:40:12,112
DIFFERENT STAGES OF WAVES HAVE

1272
00:40:12,112 --> 00:40:14,814
DIFFERENT SPATIOTEMPORAL

1273
00:40:14,814 --> 00:40:17,017
PROPERTIES AND THERE'S TRANSIENT

1274
00:40:17,017 --> 00:40:18,818
ELEMENTS SUCH AS VOLUME RELEASE

1275
00:40:18,818 --> 00:40:19,686
OF NEUROTRANSMITTER IMPORTANT

1276
00:40:19,686 --> 00:40:20,320
FOR DRIVING THIS.

1277
00:40:20,320 --> 00:40:22,289
THAT RETINAL ACTIVITY HAS BEEN

1278
00:40:22,289 --> 00:40:26,259
IMPLICATED IN THE WIRE FG DS

1279
00:40:26,259 --> 00:40:27,694
CIRCUITS SETTING EXCITABILITY OF

1280
00:40:27,694 --> 00:40:31,164
CELLS BUT NOT DIFFERENTIATION OF

1281
00:40:31,164 --> 00:40:31,865
CELL TYPES.

1282
00:40:31,865 --> 00:40:33,833
SO WHY ARE WAVES DOING ANY OF

1283
00:40:33,833 --> 00:40:34,601
THESE THINGS?

1284
00:40:34,601 --> 00:40:35,602
WHAT ABOUT WAVES IS IMPORTANT

1285
00:40:35,602 --> 00:40:39,973
FOR SETTING UP ANY OF THESE

1286
00:40:39,973 --> 00:40:40,540
CIRCUITS?

1287
00:40:40,540 --> 00:40:42,742
THE IDEA THAT THE FIELD HAS SORT

1288
00:40:42,742 --> 00:40:44,177
OF COME TO SETTLE ON IS THE IDEA

1289
00:40:44,177 --> 00:40:45,612
IS, WELL, DIFFERENT FEATURES OF

1290
00:40:45,612 --> 00:40:47,147
WAVES MIGHT BE IMPORTANT FOR

1291
00:40:47,147 --> 00:40:49,115
SETTING UP DIFFERENT ASPECTS OF

1292
00:40:49,115 --> 00:40:50,550
DIFFERENT MAPS.

1293
00:40:50,550 --> 00:40:53,953
SO FOR EXAMPLE, THIS IS THE

1294
00:40:53,953 --> 00:40:54,721
RETINOTOPIC REFINEMENT.

1295
00:40:54,721 --> 00:40:56,122
THE IDEA HERE IS THAT WELL, IF

1296
00:40:56,122 --> 00:40:57,590
YOU HAVE PROPAGATING ACTIVITY,

1297
00:40:57,590 --> 00:41:00,126
YOU'RE GOING TO HAVE NEIGHBORING

1298
00:41:00,126 --> 00:41:01,227
CELLS THAT ARE MORE CORRELATED

1299
00:41:01,227 --> 00:41:02,862
IN THEIR FIRING THAN DISTANT

1300
00:41:02,862 --> 00:41:07,801
CELLS SO THERE'S INFORMATION

1301
00:41:07,801 --> 00:41:12,639
ABOUT RETINOTOWY THPY THAT LEADO

1302
00:41:12,639 --> 00:41:13,973
THIS SORT OF REFINEMENT.

1303
00:41:13,973 --> 00:41:15,875
IF WE HAVE FOUR RETINAL GANGLION

1304
00:41:15,875 --> 00:41:18,244
CELLS THAT ARE TRANSIENTLY

1305
00:41:18,244 --> 00:41:20,213
CONNECTED TO TWO TACTILE NEURAL

1306
00:41:20,213 --> 00:41:21,381
TARGET CELLS, IF INITIALLY

1307
00:41:21,381 --> 00:41:24,451
THEY'RE MAKING A LOT OF

1308
00:41:24,451 --> 00:41:30,190
CONNECTIONS USING -- BROADLY U 

1309
00:41:30,190 --> 00:41:32,859
USING CELLS THAT ARE FIRED

1310
00:41:32,859 --> 00:41:34,394
TOGETHER, WIRED TOGETHER, YOU'RE

1311
00:41:34,394 --> 00:41:35,929
GOING TO GET THIS KIND OF MATURE

1312
00:41:35,929 --> 00:41:37,697
PATTERN WHERE YOU GET

1313
00:41:37,697 --> 00:41:38,365
RETINOTOPIC REFINEMENT.

1314
00:41:38,365 --> 00:41:40,066
SO THIS IDEA THAT A PROPAGATING

1315
00:41:40,066 --> 00:41:43,970
WAVE IS IMPORTANT FOR

1316
00:41:43,970 --> 00:41:44,504
RETINOTOPY.

1317
00:41:44,504 --> 00:41:47,907
FOR EYE SPECIFIC SEGREGATIONS,

1318
00:41:47,907 --> 00:41:49,242
YOU HAVE STRONG CORRELATIONS

1319
00:41:49,242 --> 00:41:50,977
WITHIN A RETINA BUT VERY WEAK

1320
00:41:50,977 --> 00:41:52,412
CORRELATIONS ACROSS A RETINA.

1321
00:41:52,412 --> 00:41:54,614
ONE RETINA WILL FIRE A WAVE AND

1322
00:41:54,614 --> 00:41:56,282
IT'S SILENT FOR A MINUTE,

1323
00:41:56,282 --> 00:41:57,584
CHANCES ARE THE OTHER RETINA

1324
00:41:57,584 --> 00:41:58,585
WILL FIRE DURING THAT

1325
00:41:58,585 --> 00:41:59,786
INTERVENING TIME.

1326
00:41:59,786 --> 00:42:01,588
SO THE LACK OF -- THE LOW

1327
00:42:01,588 --> 00:42:04,424
FREQUENCY OF WAVES MIGHT BE

1328
00:42:04,424 --> 00:42:06,393
IMPORTANT FOR EYE-SPECIFIC

1329
00:42:06,393 --> 00:42:07,494
SEGREGATION.

1330
00:42:07,494 --> 00:42:09,028
SO THERE'S A NEW FEATURE OF

1331
00:42:09,028 --> 00:42:10,530
WAVES THAT WE'VE BEEN TALKING A

1332
00:42:10,530 --> 00:42:13,266
LOT ABOUT THE FIELD AND THAT HAS

1333
00:42:13,266 --> 00:42:16,035
TO DO WITH SOMETHING THAT IS THE

1334
00:42:16,035 --> 00:42:17,370
PROPAGATION BIAS OF RETINAL

1335
00:42:17,370 --> 00:42:17,570
WAVES.

1336
00:42:17,570 --> 00:42:18,705
IT TURNS OUT THAT RETINAL WAVES,

1337
00:42:18,705 --> 00:42:20,140
THEY LOOKED RANDOM AND SOME OF

1338
00:42:20,140 --> 00:42:21,474
THE VIDEOS I WAS SHOWING YOU,

1339
00:42:21,474 --> 00:42:25,311
BUT IT TURNS OUT MOST WAVES

1340
00:42:25,311 --> 00:42:26,613
PROPAGATE NASALLY ON THE RETINA

1341
00:42:26,613 --> 00:42:28,248
AND THAT'S ACTUALLY REPRESENTS

1342
00:42:28,248 --> 00:42:28,848
OPTIC FLOW.

1343
00:42:28,848 --> 00:42:31,217
SO THE IDEA IS THAT MAYBE

1344
00:42:31,217 --> 00:42:33,319
RETINAL WAVES HAVE

1345
00:42:33,319 --> 00:42:35,722
EVOLUTIONARILY COME ABOUT

1346
00:42:35,722 --> 00:42:37,557
BECAUSE MAMMALS DON'T MOVE

1347
00:42:37,557 --> 00:42:38,491
DURING THIS PERIOD OF

1348
00:42:38,491 --> 00:42:40,794
DEVELOPMENT AS OPPOSED TO SAY

1349
00:42:40,794 --> 00:42:41,327
FROGS.

1350
00:42:41,327 --> 00:42:42,929
FROGS DON'T HAVE RETINAL WAVES,

1351
00:42:42,929 --> 00:42:44,030
THEY HAVE VISION, AT THE SAME

1352
00:42:44,030 --> 00:42:46,566
TIME WHEN THE RETINA IS WIRING

1353
00:42:46,566 --> 00:42:48,101
UP, THEY HAVE OPTIC FLOW BECAUSE

1354
00:42:48,101 --> 00:42:49,102
THEY'RE CONSTANTLY SWIMMING.

1355
00:42:49,102 --> 00:42:50,437
SO THIS IDEA THAT THERE MIGHT BE

1356
00:42:50,437 --> 00:42:53,706
A PROPAGATION BIAS THAT RETINAL

1357
00:42:53,706 --> 00:42:55,141
WAVES GIVE US A SIGNATURE OF

1358
00:42:55,141 --> 00:42:59,846
OPTIC FLOW BEFORE YOU HAVE ANY

1359
00:42:59,846 --> 00:43:00,947
EXPERIENCE IN THIS.

1360
00:43:00,947 --> 00:43:02,949
OPTIC FLOW IS SOMETHING WE'VE

1361
00:43:02,949 --> 00:43:04,484
DESCRIBED, WHAT'S CALLED THE

1362
00:43:04,484 --> 00:43:05,785
ROSE PLOT WHERE YOU HAVE MORE

1363
00:43:05,785 --> 00:43:08,087
WAVES PROPAGATING NASAL ON THE

1364
00:43:08,087 --> 00:43:11,157
RETINA VERSUS THE OTHER

1365
00:43:11,157 --> 00:43:13,293
DIRECTIONS, AND THIS IS

1366
00:43:13,293 --> 00:43:18,631
SOMETHING MIKE CRAIR'S LAB IS

1367
00:43:18,631 --> 00:43:19,933
INVESTIGATING, THAT HE'S ALSO

1368
00:43:19,933 --> 00:43:21,067
SEEN PROPAGATING UP TO THE

1369
00:43:21,067 --> 00:43:21,568
TECTUM.

1370
00:43:21,568 --> 00:43:24,471
SO THERE IS THIS PROPAGATION

1371
00:43:24,471 --> 00:43:26,673
BIAS OF RETINAL WAVES AND THAT

1372
00:43:26,673 --> 00:43:27,540
MIGHT BE IMPORTANT.

1373
00:43:27,540 --> 00:43:33,546
IN FACT MIKE CRIAR'S WAVE AS

1374
00:43:33,546 --> 00:43:34,981
SHOWN IF YOU GET RID OF OPTIC

1375
00:43:34,981 --> 00:43:37,750
FLOW USING A VARIETY OF

1376
00:43:37,750 --> 00:43:39,285
MANIPULATIONS, THE PROPAGATION

1377
00:43:39,285 --> 00:43:40,954
BIAS WHICH MIMICS OPTIC FLOW,

1378
00:43:40,954 --> 00:43:44,023
THAT YOU GET RID OF DIRECTION

1379
00:43:44,023 --> 00:43:45,992
SELECTIVITY AS RECORDED IN THE

1380
00:43:45,992 --> 00:43:46,960
COLLICULUS, SO HE THINKS IT'S

1381
00:43:46,960 --> 00:43:48,094
VERY IMPORTANT FOR THAT.

1382
00:43:48,094 --> 00:43:48,428
OKAY.

1383
00:43:48,428 --> 00:43:50,296
SO TO BE COMPLETELY HONEST, I'M

1384
00:43:50,296 --> 00:43:53,566
NOT SO MUCH OF A ARE WAVES

1385
00:43:53,566 --> 00:43:55,034
IMPORTANT, I JUST CARE ABOUT HOW

1386
00:43:55,034 --> 00:43:56,236
THEY'RE GENERATED BECAUSE THAT'S

1387
00:43:56,236 --> 00:43:57,770
JUST THE KIND OF SCIENTIST I AM,

1388
00:43:57,770 --> 00:44:00,640
SO WE'VE BECOME VERY FASCINATED

1389
00:44:00,640 --> 00:44:01,975
WITH THIS QUESTION ABOUT WHAT

1390
00:44:01,975 --> 00:44:02,842
CAUSES PROPAGATION BIAS.

1391
00:44:02,842 --> 00:44:04,410
WHAT IN THE RETINA IS GOING TO

1392
00:44:04,410 --> 00:44:06,613
MAKE WAVES GO MORE NASALLY?

1393
00:44:06,613 --> 00:44:08,481
SO AS I TOLD YOU BEFORE, THERE'S

1394
00:44:08,481 --> 00:44:09,816
DIFFUSE RELEASE OF

1395
00:44:09,816 --> 00:44:12,151
NEUROTRANSMITTER.

1396
00:44:12,151 --> 00:44:12,919
NEUROTRANSMITTER IS BEING

1397
00:44:12,919 --> 00:44:13,887
RELEASED IN CLOUDS SO WHAT IS

1398
00:44:13,887 --> 00:44:17,090
THE BASIS OF THIS PROPAGATION

1399
00:44:17,090 --> 00:44:17,657
BIAS?

1400
00:44:17,657 --> 00:44:20,159
THIS HAS BEEN A PROPERTY THAT

1401
00:44:20,159 --> 00:44:22,128
MIAH PITCHER IN COLLABORATION

1402
00:44:22,128 --> 00:44:31,170
WITH DARIO TOMMASINI HAVE BEEN

1403
00:44:31,170 --> 00:44:32,839
CHARACTERIZING PROPAGATION BIAS

1404
00:44:32,839 --> 00:44:34,908
AND TESTING SOME BIASES.

1405
00:44:34,908 --> 00:44:36,676
ONE WAY YOU MIGHT GET

1406
00:44:36,676 --> 00:44:37,644
PROPAGATION BIAS IS YOU HAVE

1407
00:44:37,644 --> 00:44:39,646
MORE WAVES INITIATE -- IF THEY

1408
00:44:39,646 --> 00:44:40,713
ALL START ON ONE SIDE, THEN

1409
00:44:40,713 --> 00:44:41,748
YOU'RE GOING TO GET MORE GOING

1410
00:44:41,748 --> 00:44:42,916
THIS WAY.

1411
00:44:42,916 --> 00:44:45,151
SO THAT'S ONE POSSIBILITY.

1412
00:44:45,151 --> 00:44:46,119
THE OTHER POSSIBILITY IS THAT NO

1413
00:44:46,119 --> 00:44:47,120
MATTER WHERE THEY START, THEY

1414
00:44:47,120 --> 00:44:48,755
ALWAYS SEEM TO GO NASALLY, AND

1415
00:44:48,755 --> 00:44:51,224
THAT'S SOMETHING THAT WE CAN

1416
00:44:51,224 --> 00:44:54,060
DETERMINE EXPERIMENTALLY.

1417
00:44:54,060 --> 00:44:55,295
SO WE WANT TO ASK THIS QUESTION

1418
00:44:55,295 --> 00:44:58,865
ABOUT WHAT ARE THE -- IF THERE

1419
00:44:58,865 --> 00:45:00,233
IS AN ASYMMETRIC -- NO MATTER

1420
00:45:00,233 --> 00:45:02,201
WHERE IT STARTS, IT ALWAYS GOES

1421
00:45:02,201 --> 00:45:02,835
NASALLY, THERE HAS TO BE

1422
00:45:02,835 --> 00:45:03,770
SOMETHING IN THAT CIRCUIT THAT

1423
00:45:03,770 --> 00:45:05,505
IS CAUSING THAT BIAS FOR THEM TO

1424
00:45:05,505 --> 00:45:08,041
GO THAT DIRECTION.

1425
00:45:08,041 --> 00:45:09,475
SO WHAT'S CAUSING THOSE THINGS?

1426
00:45:09,475 --> 00:45:11,044
SO THE WAY THEY'VE BEEN GETTING

1427
00:45:11,044 --> 00:45:13,212
AT THIS IS USING -- SO YOU WERE

1428
00:45:13,212 --> 00:45:16,282
SEEING AN EXAMPLE OF A WAVE

1429
00:45:16,282 --> 00:45:17,784
THAT'S PROPAGATING AND HAS -- IF

1430
00:45:17,784 --> 00:45:19,152
YOU LOOK AT ITS CENTER OF MASS,

1431
00:45:19,152 --> 00:45:22,221
IT'S GOT THIS PROPAGATION

1432
00:45:22,221 --> 00:45:22,956
CONVOLUTED PATHWAY.

1433
00:45:22,956 --> 00:45:24,290
WE JUST GO FROM START TO FINISH

1434
00:45:24,290 --> 00:45:25,792
AND THAT'S HOW WE FIGURE OUT

1435
00:45:25,792 --> 00:45:28,628
WHAT DIRECTION IT'S MOVING.

1436
00:45:28,628 --> 00:45:30,096
AND SO WHEN WE DO THAT, THIS IS

1437
00:45:30,096 --> 00:45:33,032
WHAT WE FIND.

1438
00:45:33,032 --> 00:45:36,235
SO FIRST WE FIND INDEED THERE IS

1439
00:45:36,235 --> 00:45:38,137
AN INITIATION SITE BIAS.

1440
00:45:38,137 --> 00:45:39,339
WHAT YOU'RE LOOKING AT HERE IS

1441
00:45:39,339 --> 00:45:40,873
THE DENSITY OF INITIATION SITES,

1442
00:45:40,873 --> 00:45:42,942
AND MANY MORE WAVES START IN THE

1443
00:45:42,942 --> 00:45:45,612
TEMPLE EDGE OF THE RETINA.

1444
00:45:45,612 --> 00:45:46,879
SO THAT ABSOLUTELY SEEMS TO BE

1445
00:45:46,879 --> 00:45:47,146
TRUE.

1446
00:45:47,146 --> 00:45:49,148
SOME BUT NOT ALL OF THEM SEEM TO

1447
00:45:49,148 --> 00:45:49,949
START THERE.

1448
00:45:49,949 --> 00:45:51,050
AND IN FACT, WHAT YOU'RE LOOKING

1449
00:45:51,050 --> 00:45:53,886
AT HERE ARE THE MANY -- THERE

1450
00:45:53,886 --> 00:45:55,154
ARE A WHOLE BUNCH OF WAVES HERE

1451
00:45:55,154 --> 00:45:56,322
THAT STARTED IN THE LEFT HALF OF

1452
00:45:56,322 --> 00:45:57,523
THE RETINA, AND THEY ALSO SEEM

1453
00:45:57,523 --> 00:45:59,993
TO HAVE THIS PROPAGATION BIAS.

1454
00:45:59,993 --> 00:46:04,464
SO IT DOESN'T SEEM TO BE

1455
00:46:04,464 --> 00:46:07,100
AFFECTED BY -- SO THERE IS AN

1456
00:46:07,100 --> 00:46:11,237
INITIATION BIAS BUT THERE ALSO

1457
00:46:11,237 --> 00:46:13,339
SEEMS TO BE A LOCAL PROPAGATION

1458
00:46:13,339 --> 00:46:13,806
BIAS.

1459
00:46:13,806 --> 00:46:14,841
SO WHAT'S CAUSING THIS?

1460
00:46:14,841 --> 00:46:18,011
WHAT IS CAUSING THIS -- IS IT A

1461
00:46:18,011 --> 00:46:19,112
GRADIENT OF EXCITATION?

1462
00:46:19,112 --> 00:46:23,583
IS IT A GRADIENT OF INHIBITION?

1463
00:46:23,583 --> 00:46:25,752
WHAT MIKE CRIAR'S LAB AND

1464
00:46:25,752 --> 00:46:27,587
ACTUALLY A COUPLE OTHER LABS

1465
00:46:27,587 --> 00:46:34,994
VERY RECENTLY A AT CONFERENCES,

1466
00:46:34,994 --> 00:46:38,031
WE'VE TALKED ABOUT THE START

1467
00:46:38,031 --> 00:46:44,303
BURST AMACRINE CELLS RELEASING

1468
00:46:44,303 --> 00:46:45,938
ACETYLCHOLINE -- IT RELEASES

1469
00:46:45,938 --> 00:46:47,306
ACETYLCHOLINE AND GABA, THAT'S

1470
00:46:47,306 --> 00:46:49,175
NOT WHY THEY THINK THAT BUT IT'S

1471
00:46:49,175 --> 00:46:50,810
BOTH EXCITATORY AND INHIBITORY

1472
00:46:50,810 --> 00:46:53,446
SO IT COULD DO EITHER OF OUR

1473
00:46:53,446 --> 00:46:54,213
HYPOTHESES.

1474
00:46:54,213 --> 00:46:55,682
IT'S KNOWN TO BE ASYMMETRICALLY

1475
00:46:55,682 --> 00:46:57,850
WIRED INTO THE RETINA, THAT'S

1476
00:46:57,850 --> 00:46:58,951
IMPORTANT FOR DIRECTION

1477
00:46:58,951 --> 00:47:00,219
SELECTIVITY, AND KILLING THESE

1478
00:47:00,219 --> 00:47:04,390
CELLS OR THERE'S A MU TAKE IN

1479
00:47:04,390 --> 00:47:05,358
THESE CELLS THAT IT DOESN'T

1480
00:47:05,358 --> 00:47:06,559
MATTER WHAT THE MUTATION IS BUT

1481
00:47:06,559 --> 00:47:09,462
JUST A MUTATION IN THE CELL

1482
00:47:09,462 --> 00:47:11,531
ACTUALLY MIKE CRIAR'S LAB HAS

1483
00:47:11,531 --> 00:47:13,433
SHOWN BOTH THOSE CASES YOU GET

1484
00:47:13,433 --> 00:47:14,233
LESS PROPAGATION BIAS.

1485
00:47:14,233 --> 00:47:15,735
SO IF YOU KILL THE CELL OR DO A

1486
00:47:15,735 --> 00:47:17,170
MUTATION IN THE CELL THAT GETS

1487
00:47:17,170 --> 00:47:20,440
RID OF DIRECTION SELECTIVITY,

1488
00:47:20,440 --> 00:47:22,809
THAT GETS -- WE WANT TO KNOW --

1489
00:47:22,809 --> 00:47:24,644
AND THEY SAID THAT ALSO SEEMS TO

1490
00:47:24,644 --> 00:47:27,046
GET RID OF PROPAGATION BIAS.

1491
00:47:27,046 --> 00:47:31,350
SO WE THINK THE CELL IS INVOLVED

1492
00:47:31,350 --> 00:47:34,654
AND WE'RE TRYING TO TEST IS IT

1493
00:47:34,654 --> 00:47:35,555
EXCITATION OR INHIBITION FROM

1494
00:47:35,555 --> 00:47:36,255
THE CELL.

1495
00:47:36,255 --> 00:47:38,224
SO THE FIRST THING WE DID IS WE

1496
00:47:38,224 --> 00:47:40,960
HAVE OUR MOUSE, SO IT RELEASES

1497
00:47:40,960 --> 00:47:41,894
ACETYLCHOLINE SO WE HAVE A MOUSE

1498
00:47:41,894 --> 00:47:43,763
THAT IS LACKING THE BETA

1499
00:47:43,763 --> 00:47:45,932
2 SUBUNIT OF NICOTINIC

1500
00:47:45,932 --> 00:47:47,400
ACETYLCHOLINE RECEPTORS AND WE

1501
00:47:47,400 --> 00:47:48,735
FIND UNFORTUNATELY THAT THE

1502
00:47:48,735 --> 00:47:49,802
PROPAGATION BIAS WE SEE IN WILD

1503
00:47:49,802 --> 00:47:51,938
TYPE IS STILL PRESERVED IN THE

1504
00:47:51,938 --> 00:47:52,371
BETA 2 KNOCKOUT.

1505
00:47:52,371 --> 00:47:54,340
SO IT DOESN'T SEEM TO BE AT

1506
00:47:54,340 --> 00:47:56,109
LEAST MEDIATED BY THIS NICOTINIC

1507
00:47:56,109 --> 00:47:57,477
RECEPTOR.

1508
00:47:57,477 --> 00:47:59,078
SO THEN WE THOUGHT WELL, MAYBE

1509
00:47:59,078 --> 00:48:00,747
IT'S GABA, AND INDEED, WHEN WE

1510
00:48:00,747 --> 00:48:02,982
PUT ON GABA-A RECEPTOR BLOCKERS,

1511
00:48:02,982 --> 00:48:06,018
THE WAVES GO NUTS, BUT IN THERE

1512
00:48:06,018 --> 00:48:07,220
GOING NUTS, THEY ALSO SEEM TO

1513
00:48:07,220 --> 00:48:08,521
LOSE THEIR PROPAGATION BIAS.

1514
00:48:08,521 --> 00:48:09,822
THEY MIGHT HAVE A LITTLE BIT OF

1515
00:48:09,822 --> 00:48:12,992
IT LEFT BUT THEY SEEM TO LOSE

1516
00:48:12,992 --> 00:48:13,693
THEIR PROPAGATION BIAS.

1517
00:48:13,693 --> 00:48:14,894
SO THAT'S CONSISTENT WITH THE

1518
00:48:14,894 --> 00:48:16,662
IDEA THAT IT'S MEDIATED BY THE

1519
00:48:16,662 --> 00:48:18,097
RELEASE OF GABA RECEPTORS.

1520
00:48:18,097 --> 00:48:20,733
YOU CAN SEE PROPAGATION BIAS IS

1521
00:48:20,733 --> 00:48:23,669
NOT AS STRONG IN THE PRESENCE OF

1522
00:48:23,669 --> 00:48:24,737
GABA-A ANTAGONISTS.

1523
00:48:24,737 --> 00:48:26,739
BUT THEN WE TOOK ADVANTAGE OF A

1524
00:48:26,739 --> 00:48:35,148
MOUSE LINE THAT WAS GENERATED B-

1525
00:48:35,148 --> 00:48:40,419
WHERE YOU CAN RELEASE GABA JUST

1526
00:48:40,419 --> 00:48:41,454
FROM THE STARBURST CELLS.

1527
00:48:41,454 --> 00:48:43,523
WE LOOK JUST AT THAT MOUSE, NO

1528
00:48:43,523 --> 00:48:45,091
GABA RELEASE FROM STARBURST

1529
00:48:45,091 --> 00:48:47,160
CELLS, IT STILL HAS PROPAGATION

1530
00:48:47,160 --> 00:48:48,127
BIAS, AND SO WE DON'T KNOW THE

1531
00:48:48,127 --> 00:48:48,594
ANSWER.

1532
00:48:48,594 --> 00:48:49,562
SORRY.

1533
00:48:49,562 --> 00:48:51,264
SO WE'RE STILL WORKING ON IT.

1534
00:48:51,264 --> 00:48:52,999
BUT I WANTED TO THROW THAT OUT

1535
00:48:52,999 --> 00:48:54,467
THERE AS A PUZZLE FOR YOU

1536
00:48:54,467 --> 00:48:55,735
CIRCUIT PEOPLE OUT THERE, IF YOU

1537
00:48:55,735 --> 00:48:57,203
HAVE ANY IDEAS IN WHAT WE CAN

1538
00:48:57,203 --> 00:48:57,770
PURSUE.

1539
00:48:57,770 --> 00:48:58,971
OKAY.

1540
00:48:58,971 --> 00:49:00,840
OKAY.

1541
00:49:00,840 --> 00:49:02,308
SO -- AND ONE OF THE

1542
00:49:02,308 --> 00:49:04,410
POSSIBILITIES IS THAT, AGAIN, IT

1543
00:49:04,410 --> 00:49:06,379
COULD BE ACETYLCHOLINE RECEPTORS

1544
00:49:06,379 --> 00:49:08,581
THAT ARE NOT THE BAY A

1545
00:49:08,581 --> 00:49:10,316
2 CONTAINING ONES AND THOSE ARE

1546
00:49:10,316 --> 00:49:16,856
EXPERIMENTS THAT MAIAH IS DOING

1547
00:49:16,856 --> 00:49:18,057
THIS WEEK SO I CAN GET BACK TO

1548
00:49:18,057 --> 00:49:18,891
SOME OF YOU THAT CARE ABOUT

1549
00:49:18,891 --> 00:49:19,158
THIS.

1550
00:49:19,158 --> 00:49:20,359
SO THE LAST THING I WANT TO TALK

1551
00:49:20,359 --> 00:49:21,327
ABOUT IS A REALLY NEW DIRECTION

1552
00:49:21,327 --> 00:49:22,161
FOR THE LAB.

1553
00:49:22,161 --> 00:49:24,997
THIS WAS PROJECTS THAT WERE

1554
00:49:24,997 --> 00:49:26,999
INITIATED BY A GRADUATE STUDENT

1555
00:49:26,999 --> 00:49:28,568
IN THE LAB, WHO'S A CELL

1556
00:49:28,568 --> 00:49:29,869
BIOLOGIST, AND IT WAS ALL --

1557
00:49:29,869 --> 00:49:30,837
STARTED BY TWO THINGS.

1558
00:49:30,837 --> 00:49:32,705
ONE WAS THIS IMAGING EXPERIMENT

1559
00:49:32,705 --> 00:49:35,474
THAT WAS DONE, SO THIS IS A

1560
00:49:35,474 --> 00:49:36,876
CALCIUM IMAGING EXPERIMENT

1561
00:49:36,876 --> 00:49:37,910
LOOKING AT WAVES BUT YOU CAN SEE

1562
00:49:37,910 --> 00:49:39,045
ON THE SURFACE OF THE RETINA,

1563
00:49:39,045 --> 00:49:40,446
THERE IS SOME VASCULATURE, AND

1564
00:49:40,446 --> 00:49:41,848
THAT YOU CAN SEE THAT WHEN A

1565
00:49:41,848 --> 00:49:43,049
WAVE SORT OF GOES THROUGH THAT

1566
00:49:43,049 --> 00:49:44,784
REGION, THAT THERE'S A LOT OF

1567
00:49:44,784 --> 00:49:46,485
CALCIUM ACTIVITY THAT'S GOING ON

1568
00:49:46,485 --> 00:49:47,920
AROUND THE VASCULATURE.

1569
00:49:47,920 --> 00:49:49,222
I DON'T KNOW IF YOU CAN SEE IT

1570
00:49:49,222 --> 00:49:49,422
HERE.

1571
00:49:49,422 --> 00:49:50,656
IT'S REALLY BEAUTIFUL ON MY

1572
00:49:50,656 --> 00:49:50,957
SCREEN.

1573
00:49:50,957 --> 00:49:53,759
THIS LED TO THIS IDEA THAT

1574
00:49:53,759 --> 00:49:54,861
MAYBE -- IS THERE ANY SIGNALING

1575
00:49:54,861 --> 00:49:58,030
FROM NEURONS OR GLIA TO THE

1576
00:49:58,030 --> 00:50:00,399
VASCULATURE DURING THE PERIOD OF

1577
00:50:00,399 --> 00:50:01,934
TIME WHEN THE VASCULATURE IS

1578
00:50:01,934 --> 00:50:02,368
GROWING.

1579
00:50:02,368 --> 00:50:04,403
AND IT'S BECAUSE THE VASCULATURE

1580
00:50:04,403 --> 00:50:05,972
IS GROWING AT THE SAME TIME THAT

1581
00:50:05,972 --> 00:50:08,107
THERE ARE RETINAL WAVES.

1582
00:50:08,107 --> 00:50:09,508
SO LET ME JUST INTRODUCE YOU TO

1583
00:50:09,508 --> 00:50:12,144
THE VASCULATURE OF THE RETINA SO

1584
00:50:12,144 --> 00:50:13,512
ANOTHER REASON WHY -- WELL, I

1585
00:50:13,512 --> 00:50:16,249
LOVE THIS PROJECT IS BECAUSE THE

1586
00:50:16,249 --> 00:50:17,016
VASCULATURE IN THE MOUSE RETINA

1587
00:50:17,016 --> 00:50:19,418
IS GORGEOUS, AND SO -- AND

1588
00:50:19,418 --> 00:50:21,120
YOU'LL SEE IT APPEARS IN THREE

1589
00:50:21,120 --> 00:50:22,455
LAYERS.

1590
00:50:22,455 --> 00:50:24,724
THERE IS A SUPERFICIAL LAYER

1591
00:50:24,724 --> 00:50:26,259
THAT'S ALONG THE GANGLION CELL

1592
00:50:26,259 --> 00:50:26,792
LAYER.

1593
00:50:26,792 --> 00:50:28,728
THERE IS A DEEP VASCULATURE, AND

1594
00:50:28,728 --> 00:50:30,563
THEN THERE'S AN INTERMEDIATE

1595
00:50:30,563 --> 00:50:31,030
VASCULATURE.

1596
00:50:31,030 --> 00:50:33,532
AND THEY'RE ALL CONNECTED BY

1597
00:50:33,532 --> 00:50:36,636
THESE DIVING VESSELS THAT ARE

1598
00:50:36,636 --> 00:50:37,303
EXTREMELY PERPENDICULAR GOING

1599
00:50:37,303 --> 00:50:38,170
THROUGH THE RETINA.

1600
00:50:38,170 --> 00:50:39,772
SO WHAT I'M GOING TO SHOW YOU IS

1601
00:50:39,772 --> 00:50:42,174
A CONFOCAL IMAGE, HOPEFULLY THIS

1602
00:50:42,174 --> 00:50:44,343
WILL WORK, OF THE VASCULATURE

1603
00:50:44,343 --> 00:50:45,678
THAT'S BEEN LABELED WITH AN

1604
00:50:45,678 --> 00:50:45,945
ANTIBODY.

1605
00:50:45,945 --> 00:50:47,480
THIS IS THE SUPERFICIAL

1606
00:50:47,480 --> 00:50:48,681
VASCULATURE AND IT'S GOING BACK,

1607
00:50:48,681 --> 00:50:49,882
AND THEN YOU CAN SEE THOSE ARE

1608
00:50:49,882 --> 00:50:52,318
THE DIVING VESSELS, THAT'S THE

1609
00:50:52,318 --> 00:50:53,753
INTERMEDIATE VASCULATURE, DIVING

1610
00:50:53,753 --> 00:50:55,221
VESSELS AND THEN YOU CAN SEE THE

1611
00:50:55,221 --> 00:50:56,088
DEEP VA CLA TOUR.

1612
00:50:56,088 --> 00:50:57,757
IT'S INCREDIBLY WELL ORGANIZED.

1613
00:50:57,757 --> 00:51:01,961
IF YOU LOOK AT IT, HERE'S THE

1614
00:51:01,961 --> 00:51:03,262
SUPERFICIAL VASCULATURE, DEEP

1615
00:51:03,262 --> 00:51:04,363
AND IMMEDIATE.

1616
00:51:04,363 --> 00:51:06,098
THEY EMERGE IN A VERY

1617
00:51:06,098 --> 00:51:07,066
STEREOTYPICAL TIME COURSE DURING

1618
00:51:07,066 --> 00:51:08,000
DEVELOPMENT.

1619
00:51:08,000 --> 00:51:10,169
THE SUPERFICIAL VASCULATURE

1620
00:51:10,169 --> 00:51:12,171
GROWS OUT FIRST BETWEEN

1621
00:51:12,171 --> 00:51:14,507
POSTNATAL DAY ZERO, DONE BY

1622
00:51:14,507 --> 00:51:16,075
POSTNATAL DAY 9.

1623
00:51:16,075 --> 00:51:18,244
THEN THE DEEP VASCULATURE

1624
00:51:18,244 --> 00:51:22,381
EMERGES DURING THE SECOND WEEK.

1625
00:51:22,381 --> 00:51:23,516
YOU CAN SEE THIS IS ALL

1626
00:51:23,516 --> 00:51:24,150
HAPPENING AT THE SAME TIME AS

1627
00:51:24,150 --> 00:51:26,052
THERE ARE RETINAL WAVES.

1628
00:51:26,052 --> 00:51:27,820
SO WE REALLY WANTED TO KNOW IF

1629
00:51:27,820 --> 00:51:29,288
NEURAL SIGNALING WAS SOMEHOW

1630
00:51:29,288 --> 00:51:29,956
INFLUENCING THIS PROCESS.

1631
00:51:29,956 --> 00:51:32,458
I DO WANT TO MAKE NOTE IN THIS

1632
00:51:32,458 --> 00:51:33,626
DIAGRAM, THERE'S ALSO A GLIAL

1633
00:51:33,626 --> 00:51:35,161
CELL AND I'M GOING TO TALK ABOUT

1634
00:51:35,161 --> 00:51:36,462
THAT GLIAL CELL IN JUST A

1635
00:51:36,462 --> 00:51:38,864
MOMENT.

1636
00:51:38,864 --> 00:51:44,403
SO WE CHARACTERIZES THE

1637
00:51:44,403 --> 00:51:45,638
MATURATION OF THE VASCULATURE,

1638
00:51:45,638 --> 00:51:48,240
SO HERE'S THE SUPERVISOR VISUAL

1639
00:51:48,240 --> 00:51:52,011
VASCULATURE AS A FUDGES FUNCTIOF

1640
00:51:52,011 --> 00:51:53,112
AGE, AGE IS GOING DOWN.

1641
00:51:53,112 --> 00:51:57,016
WE MEASURED THE DENSITY OF THE

1642
00:51:57,016 --> 00:51:58,384
VASCULAR, BOTH PROXIMAL AND

1643
00:51:58,384 --> 00:51:59,919
DISTAL, AND THEN FOR EACH AGE,

1644
00:51:59,919 --> 00:52:04,190
EACH LINE HERE IS A RETINA, THIS

1645
00:52:04,190 --> 00:52:05,458
IS A WAY TO REPRESENT WHAT THE

1646
00:52:05,458 --> 00:52:07,860
DENSITY IS ACROSS THE

1647
00:52:07,860 --> 00:52:08,160
VASCULATURE.

1648
00:52:08,160 --> 00:52:10,296
WE THEN DO IT FOR THE DEEP AND

1649
00:52:10,296 --> 00:52:11,630
THEN THE INTERMEDIATE

1650
00:52:11,630 --> 00:52:12,298
VASCULATURE.

1651
00:52:12,298 --> 00:52:14,133
ONE OF THE THINGS I LIKE THAT

1652
00:52:14,133 --> 00:52:14,500
REPRESENTATION.

1653
00:52:14,500 --> 00:52:15,835
ONE OF THE THINGS I ACTUALLY

1654
00:52:15,835 --> 00:52:16,836
FOUND REMARKABLE, THIS IS KIND

1655
00:52:16,836 --> 00:52:19,038
OF AN ASIDE BUT FOR -- I STILL

1656
00:52:19,038 --> 00:52:20,172
THOUGHT IT WAS REMARKABLE, IS

1657
00:52:20,172 --> 00:52:21,407
THAT IF YOU LOOK AT THE DENSITY

1658
00:52:21,407 --> 00:52:24,543
OF THE VASCULATURE ACROSS THE

1659
00:52:24,543 --> 00:52:26,078
WHOLE RETINA EVEN DURING

1660
00:52:26,078 --> 00:52:27,446
DEVELOPMENT, IT IS INCREDIBLY

1661
00:52:27,446 --> 00:52:27,680
UNIFORM.

1662
00:52:27,680 --> 00:52:29,181
NO MATTER WHERE YOU ARE IN THE

1663
00:52:29,181 --> 00:52:30,583
RETINA, EVEN AS IT'S GROWING, IT

1664
00:52:30,583 --> 00:52:32,418
HAS THIS INCREDIBLE UNIFORM

1665
00:52:32,418 --> 00:52:33,619
DENSITY ACROSS THE RETINA, WHICH

1666
00:52:33,619 --> 00:52:34,954
I JUST FIND REMARKABLE.

1667
00:52:34,954 --> 00:52:37,823
THIS IS WHEN LIKE THE PHYSICIST

1668
00:52:37,823 --> 00:52:39,358
IN ONE COMES OUT, LIKE WHAT IS

1669
00:52:39,358 --> 00:52:40,760
REGULATING SORT OF THE

1670
00:52:40,760 --> 00:52:42,228
INCREDIBLE REGULARITY OF THAT.

1671
00:52:42,228 --> 00:52:43,863
THIS IS JUST AN ASIDE, MAYBE

1672
00:52:43,863 --> 00:52:44,864
WE'LL UNDERSTAND HOW THAT

1673
00:52:44,864 --> 00:52:47,133
EMERGES BUT YOU CAN SEE POSE

1674
00:52:47,133 --> 00:52:49,635
NATAL DAY 7 THE SUPERVISOR

1675
00:52:49,635 --> 00:52:51,037
VISUAL VASCULATURE IS VERY

1676
00:52:51,037 --> 00:52:52,671
UNIFORM, NOT FULLY GROWN OUT YET

1677
00:52:52,671 --> 00:52:54,607
AND THEN WHEN YOU LOOK AT A WEEK

1678
00:52:54,607 --> 00:52:56,108
LATER, THE DEEP VASCULATURE HAS

1679
00:52:56,108 --> 00:52:57,643
GOT A HIGHER DENSITY, THE

1680
00:52:57,643 --> 00:52:59,145
SUPERVISOR VISUAL VASCULATURE IS

1681
00:52:59,145 --> 00:53:00,579
REFINED BUT THAT REFINEMENT IS

1682
00:53:00,579 --> 00:53:03,849
REALLY QUITE REMARKABLY UNIFORM.

1683
00:53:03,849 --> 00:53:04,316
OKAY.

1684
00:53:04,316 --> 00:53:05,017
THAT'S MY LITTLE ASIDE.

1685
00:53:05,017 --> 00:53:07,753
SO IF WE LOOK NOW, THIS IS

1686
00:53:07,753 --> 00:53:09,422
DEVELOPMENT, WE LOOK IN THE WILD

1687
00:53:09,422 --> 00:53:12,525
TYPE, THIS IS NOW IN THE CENTRAL

1688
00:53:12,525 --> 00:53:13,926
RETINA VERSUS THE PERIPHERAL

1689
00:53:13,926 --> 00:53:15,461
RETINA, THE SUPERFICIAL

1690
00:53:15,461 --> 00:53:16,762
VASCULATURE IS THERE, IT

1691
00:53:16,762 --> 00:53:17,830
UNDERGOES A PERIOD OF

1692
00:53:17,830 --> 00:53:20,666
REFINEMENT, THE KEEP VASCULATURE

1693
00:53:20,666 --> 00:53:22,301
EMERGES AROUND POSTNATAL DAY 8,

1694
00:53:22,301 --> 00:53:23,602
THIS IS KIND OF THE PERIPHERY,

1695
00:53:23,602 --> 00:53:24,770
IT GROWS OUT A LITTLE LATER AND

1696
00:53:24,770 --> 00:53:27,006
WE LOOKED IN THE BETA TWO --

1697
00:53:27,006 --> 00:53:29,442
THIS HAS BEEN DESCRIBED BY

1698
00:53:29,442 --> 00:53:31,444
OTHERS BEFORE, WE LOOK IN THE

1699
00:53:31,444 --> 00:53:34,480
BETA TWO KNOCKOUT AND IT LOOKS

1700
00:53:34,480 --> 00:53:35,047
PERFECTLY NORMAL.

1701
00:53:35,047 --> 00:53:37,716
SO ANOTHER -- SO I WON'T SAY

1702
00:53:37,716 --> 00:53:38,584
IT'S PERFECTLY NORMAL.

1703
00:53:38,584 --> 00:53:41,287
IT'S A LITTLE BIT DELAYED, AND

1704
00:53:41,287 --> 00:53:44,223
ACTUALLY THERE WAS EXPERIMENTS

1705
00:53:44,223 --> 00:53:49,929
DONE BY BISWAS PUBLISHED THIS

1706
00:53:49,929 --> 00:53:50,930
YEAR THAT FOUND THE DELAY.

1707
00:53:50,930 --> 00:53:52,298
SO IT SEEMS LIKE ACTIVITY IS

1708
00:53:52,298 --> 00:53:54,800
REGULATING THE PACE AT WITH IT

1709
00:53:54,800 --> 00:53:55,568
HAPPENING BUT EVERYTHING SEEMS

1710
00:53:55,568 --> 00:53:56,469
TO GET THERE IN THE END.

1711
00:53:56,469 --> 00:53:57,636
SO IT DOESN'T SEEM IMPORTANT FOR

1712
00:53:57,636 --> 00:53:58,370
THAT.

1713
00:53:58,370 --> 00:54:00,039
SO WHAT WE'RE REALLY FOCUSING ON

1714
00:54:00,039 --> 00:54:02,374
NOW IS THIS OTHER CELL TYPE, AND

1715
00:54:02,374 --> 00:54:05,211
THAT IS THIS MUELLER GLIAL CELL

1716
00:54:05,211 --> 00:54:06,846
AND WHAT ROLE IT PLAYS IN

1717
00:54:06,846 --> 00:54:07,847
DEVELOPING THE VASCULATURE.

1718
00:54:07,847 --> 00:54:09,882
THIS IS IMPORTANT BECAUSE

1719
00:54:09,882 --> 00:54:11,083
MUELLER GLIAL CELLS ARE THE LAST

1720
00:54:11,083 --> 00:54:13,385
CELLS IN THE RETINA TO MATURE.

1721
00:54:13,385 --> 00:54:18,891
THEY TRAVERSE THE ENTIRE

1722
00:54:18,891 --> 00:54:20,793
THICKNESS OF THE -- AND THEY ARE

1723
00:54:20,793 --> 00:54:22,995
GROWING OUT THESE LATERAL

1724
00:54:22,995 --> 00:54:25,397
PROCESSES DURING THE SAME

1725
00:54:25,397 --> 00:54:26,232
STAPLING OF DEVELOPMENT.

1726
00:54:26,232 --> 00:54:28,300
THIS PROJECT WAS ACTUALLY

1727
00:54:28,300 --> 00:54:29,602
COMPLETELY MOTIVATED BY A STUDY

1728
00:54:29,602 --> 00:54:33,105
THAT CAME OUT FROM -- LED BY

1729
00:54:33,105 --> 00:54:36,342
WILL GRIMES WHO IS IN DIAMOND'S

1730
00:54:36,342 --> 00:54:39,512
LAB, APPARENTLY PAPER IS BEING

1731
00:54:39,512 --> 00:54:40,613
PUBLISHED NEXT WEEK AND IT'S

1732
00:54:40,613 --> 00:54:42,615
THIS INKREDZIBLE -- WHAT WILL

1733
00:54:42,615 --> 00:54:44,183
HAS BEEN ABLE TO SHOW IS THAT

1734
00:54:44,183 --> 00:54:46,919
THIS VASCULATURE IS COMPLETELY

1735
00:54:46,919 --> 00:54:49,388
ENCHIEFED BY THE MULLER GLIAL

1736
00:54:49,388 --> 00:54:49,822
CELLS.

1737
00:54:49,822 --> 00:54:52,124
EVERYWHERE YOU LOOK AT THAT

1738
00:54:52,124 --> 00:54:52,892
VASCULATURE, WHETHER IT'S A

1739
00:54:52,892 --> 00:54:55,161
DIVING VESSEL, LATERALIZED

1740
00:54:55,161 --> 00:54:56,695
CAPILLARY BED, THERE ARE GLIAL

1741
00:54:56,695 --> 00:54:57,796
CELLS EVERYWHERE THERE.

1742
00:54:57,796 --> 00:54:59,632
THERE ARE A FEW PATCHES WHERE

1743
00:54:59,632 --> 00:55:05,004
THERE AREN'T GLIAL CELLS BUT

1744
00:55:05,004 --> 00:55:07,406
95%, WELL, 96% IS COMPLETELY

1745
00:55:07,406 --> 00:55:09,708
COVERED BY GLIAL CELLS.

1746
00:55:09,708 --> 00:55:10,910
HE KNOWS THE ANSWER TO THAT.

1747
00:55:10,910 --> 00:55:12,778
THIS IS AN EXAMPLE THAT YOU CAN

1748
00:55:12,778 --> 00:55:13,312
SEE.

1749
00:55:13,312 --> 00:55:16,549
SO EACH MULLER GLIAL CELL HAS A

1750
00:55:16,549 --> 00:55:17,850
BUNCH OF LATERAL PROCESSES

1751
00:55:17,850 --> 00:55:20,819
COMING OUT AND IT SENDS ONE

1752
00:55:20,819 --> 00:55:22,321
PROCESS TO THE VASCULATURE SO

1753
00:55:22,321 --> 00:55:24,156
THE VASCULATURE IS COVERED BY A

1754
00:55:24,156 --> 00:55:26,025
SINGLE LATERAL PROCESSES FROM A

1755
00:55:26,025 --> 00:55:27,826
WHOLE BUNCH OF MULLER GLIAL

1756
00:55:27,826 --> 00:55:28,194
CELLS.

1757
00:55:28,194 --> 00:55:28,627
IT'S BEAUTIFUL.

1758
00:55:28,627 --> 00:55:30,829
THIS IS ALL EMERGING AT THE SAME

1759
00:55:30,829 --> 00:55:31,897
TIME IN DEVELOPMENT.

1760
00:55:31,897 --> 00:55:33,699
AND WE WERE INTERESTED IN THIS

1761
00:55:33,699 --> 00:55:36,535
BECAUSE A GRADUATE STUDENT IN MY

1762
00:55:36,535 --> 00:55:39,271
LAB, JOSH, WHO LIKES HUGGING

1763
00:55:39,271 --> 00:55:41,207
THINGS, WAS STUDYING THE

1764
00:55:41,207 --> 00:55:42,308
EMERGENCE OF THE LATERAL

1765
00:55:42,308 --> 00:55:43,275
PROCESSES FROM THESE GLIAL

1766
00:55:43,275 --> 00:55:46,245
CELLS, SO HERE'S A STALK, HERE'S

1767
00:55:46,245 --> 00:55:47,947
A STALK AND THESE LATERAL

1768
00:55:47,947 --> 00:55:48,747
PROCESSES ARE COMING IN.

1769
00:55:48,747 --> 00:55:50,683
IF YOU LOOK AT THIS ONE RIGHT

1770
00:55:50,683 --> 00:55:52,885
HERE, I'M CONVINCED THIS IS

1771
00:55:52,885 --> 00:55:56,121
GROWING OUT AND GROWING AROUND A

1772
00:55:56,121 --> 00:55:59,291
BLOOD VEST W VESSEL EMERGING.

1773
00:55:59,291 --> 00:56:01,227
THESE GUYS ARE INCREDIBLY

1774
00:56:01,227 --> 00:56:02,595
MOTILE, AND SO WE WANT TO SEE

1775
00:56:02,595 --> 00:56:03,629
WHETHER OR NOT THERE'S SOME SORT

1776
00:56:03,629 --> 00:56:08,033
OF SIGNALING BETWEEN THESE GLIAL

1777
00:56:08,033 --> 00:56:09,635
CELLS AND THE VASCULATURE.

1778
00:56:09,635 --> 00:56:13,772
IF YOU LOOK AT -- SO THESE ARE

1779
00:56:13,772 --> 00:56:16,242
EXPERIMENTS BEING DONE BY SAMIRA

1780
00:56:16,242 --> 00:56:19,311
WHERE IF YOU LOOK AT THE

1781
00:56:19,311 --> 00:56:20,846
VASCULATURE -- AT THE EARLIEST

1782
00:56:20,846 --> 00:56:23,115
AGES WHERE WE CAN SEE THE DIVING

1783
00:56:23,115 --> 00:56:25,284
VESSELS, THEY'RE COMPLETELY

1784
00:56:25,284 --> 00:56:26,819
ENSHEATHED BY GLIAL CELLS.

1785
00:56:26,819 --> 00:56:29,455
THE SUPERFICIAL LAYER, THEY'RE

1786
00:56:29,455 --> 00:56:30,689
COVERED AND THE DEEP

1787
00:56:30,689 --> 00:56:31,590
VASCULATURE, THEY ALSO APPEAR TO

1788
00:56:31,590 --> 00:56:33,559
BE COVERED AND I THINK THIS IS A

1789
00:56:33,559 --> 00:56:34,693
MOVIE THAT'S NOT WORKING THAT

1790
00:56:34,693 --> 00:56:35,594
WOULD SHOW YOU THAT WHEN YOU

1791
00:56:35,594 --> 00:56:37,463
LOOK AT A VESSEL, IT'S JUST

1792
00:56:37,463 --> 00:56:38,764
LITERALLY CRAWLING UP THROUGH

1793
00:56:38,764 --> 00:56:43,969
WHERE THE MULLER GLIA ARE.

1794
00:56:43,969 --> 00:56:45,604
WE'RE REALLY INTERESTED IN THIS

1795
00:56:45,604 --> 00:56:46,605
QUESTION WHETHER SIGNALING

1796
00:56:46,605 --> 00:56:47,573
BETWEEN THESE CELL TYPES MATTER

1797
00:56:47,573 --> 00:56:48,540
AND WE'RE INTERESTED IN THIS

1798
00:56:48,540 --> 00:56:50,376
BECAUSE RETINAL WAVES, IT TURNS

1799
00:56:50,376 --> 00:56:52,745
OUT, CAUSE CALCIUM TRANSIENCE IN

1800
00:56:52,745 --> 00:56:53,846
GLIAL CELLS, SO THESE ARE A

1801
00:56:53,846 --> 00:56:55,614
WHOLE BUNCH OF GLIAL STALKS.

1802
00:56:55,614 --> 00:56:57,349
THESE ARE THERE -- I THINK YOU

1803
00:56:57,349 --> 00:56:58,751
MIGHT BE ABLE TO SEE, WHEN A

1804
00:56:58,751 --> 00:57:00,052
WAVE GOES THROUGH THE TISSUE,

1805
00:57:00,052 --> 00:57:03,489
HOPEFULLY YOU'LL BE ABLE TO SEE

1806
00:57:03,489 --> 00:57:04,323
WHEN A WAVE GOES THROUGH, YOU

1807
00:57:04,323 --> 00:57:06,392
SEE ALL THE LATERAL PROCESSES

1808
00:57:06,392 --> 00:57:10,863
GET LIT UP, AND SOME -- IN SOME

1809
00:57:10,863 --> 00:57:15,668
EXPERIMENTS THAT ARE GOING ON BY

1810
00:57:15,668 --> 00:57:17,269
ANGEL GARCIA, YOU'RE LOOKING AT

1811
00:57:17,269 --> 00:57:18,270
A DIVING VESSEL HERE.

1812
00:57:18,270 --> 00:57:20,639
WE HAVE A CALCIUM DIVE EXPRESSED

1813
00:57:20,639 --> 00:57:21,540
ONLY IN THE GLIAL CELLS AND YOU

1814
00:57:21,540 --> 00:57:22,708
CAN SEE THAT THERE ARE SOME --

1815
00:57:22,708 --> 00:57:24,777
AND THEN THIS IS NOW IN THE DEEP

1816
00:57:24,777 --> 00:57:25,644
PLEXUS AND YOU CAN SEE THAT

1817
00:57:25,644 --> 00:57:30,249
THERE IS SOME CALCIUM TRANSIENCE

1818
00:57:30,249 --> 00:57:31,784
THAT ARE HAPPENING IN THE GLIAL

1819
00:57:31,784 --> 00:57:32,484
CELLS.

1820
00:57:32,484 --> 00:57:33,686
WILL HAS SHOWN THIS BEAUTIFULLY

1821
00:57:33,686 --> 00:57:35,354
IN THE ADULT VASCULATURE, AND

1822
00:57:35,354 --> 00:57:36,555
WE'RE LOOKING TO DO THIS EARLY

1823
00:57:36,555 --> 00:57:38,157
IN DEVELOPMENT, AND OUR QUESTION

1824
00:57:38,157 --> 00:57:40,492
IS, WHO'S LEADING WHOM?

1825
00:57:40,492 --> 00:57:43,295
DO THE BLOOD VESSELS GROW UP

1826
00:57:43,295 --> 00:57:45,030
ALONG THE GLIAL CELLS, DO THE

1827
00:57:45,030 --> 00:57:46,899
GLIAL CELLS COME UP TO THE BLOOD

1828
00:57:46,899 --> 00:57:47,866
VESSELS AND WHAT IS THE

1829
00:57:47,866 --> 00:57:49,501
SIGNALING BETWEEN THE CELLS THAT

1830
00:57:49,501 --> 00:57:50,903
MEDIATE THIS PHENOMENON.

1831
00:57:50,903 --> 00:57:52,237
OKAY.

1832
00:57:52,237 --> 00:57:54,540
SO THAT'S TO SUMMARIZE TODAY.

1833
00:57:54,540 --> 00:57:56,575
RETINAL WAVES ARE BOTH SOURCE OF

1834
00:57:56,575 --> 00:57:57,543
ACTIVITY BEFORE VISION, THEY'RE

1835
00:57:57,543 --> 00:57:58,410
IMPORTANT FOR SETTING UP

1836
00:57:58,410 --> 00:57:59,845
CONNECTIONS THROUGHOUT THE

1837
00:57:59,845 --> 00:58:01,013
VISUAL SYSTEM, THEY'RE IMPORTANT

1838
00:58:01,013 --> 00:58:02,381
FOR SETTING UP SOME CIRCUITS

1839
00:58:02,381 --> 00:58:05,384
WITHIN THE RETINA, BUT NOT FOR

1840
00:58:05,384 --> 00:58:07,553
DIFFERENTIATION OF CELL TYPES.

1841
00:58:07,553 --> 00:58:08,420
THERE IS A PROPAGATION BIAS

1842
00:58:08,420 --> 00:58:10,055
WHICH IS A FEATURE OF RETINAL

1843
00:58:10,055 --> 00:58:10,622
WAVES.

1844
00:58:10,622 --> 00:58:12,358
IT'S DEPENDENT ON GABA SIGNALING

1845
00:58:12,358 --> 00:58:13,659
BUT THE ORIGINS OF IT REMAIN

1846
00:58:13,659 --> 00:58:14,960
UNKNOWN.

1847
00:58:14,960 --> 00:58:16,395
RETINAL WAVES PLAY A LIMITED

1848
00:58:16,395 --> 00:58:19,031
ROLE IN ANGIOGENESIS AND THE

1849
00:58:19,031 --> 00:58:20,299
TIME COURSE OF IT, OR A LITTLE

1850
00:58:20,299 --> 00:58:21,734
BIT IN THE TIME COURSE BUT NOT

1851
00:58:21,734 --> 00:58:23,235
IN THE OVERALL STRUCTURE BUT WE

1852
00:58:23,235 --> 00:58:24,636
THINK GLIAL SIGNALING MAY BE

1853
00:58:24,636 --> 00:58:25,938
CRUCIAL FOR GUIDING THE

1854
00:58:25,938 --> 00:58:26,772
VASCULATURE DEVELOPMENT.

1855
00:58:26,772 --> 00:58:30,109
THIS IS THE FELLER LAB.

1856
00:58:30,109 --> 00:58:31,510
AND IN A RECENT VISIT TO --

1857
00:58:31,510 --> 00:58:34,346
THERE'S A MUSEUM OF THE EYE NEAR

1858
00:58:34,346 --> 00:58:39,518
FISHERMAN'SFISHERMAN'S WHARF.

1859
00:58:39,518 --> 00:58:42,187
I THINK I'VE DESCRIBED

1860
00:58:42,187 --> 00:58:43,722
EVERYONE'S PROJECT TODAY, AND I

1861
00:58:43,722 --> 00:58:45,858
WANT TO END BY SAYING THAT,

1862
00:58:45,858 --> 00:58:47,192
AGAIN, WE'RE FUNDED BY THE

1863
00:58:47,192 --> 00:58:48,394
NATIONAL EYE INSTITUTE, AND FOR

1864
00:58:48,394 --> 00:58:49,695
THAT, I AM TREMENDOUSLY

1865
00:58:49,695 --> 00:58:50,195
GRATEFUL.

1866
00:58:50,195 --> 00:58:50,896
SO THANK YOU VERY MUCH.

1867
00:58:50,896 --> 00:59:01,073
[APPLAUSE]

1868
00:59:01,340 --> 00:59:02,574
>> THANK YOU VERY MUCH FOR
A

1869
00:59:02,574 --> 00:59:02,941
WONDERFUL TALK.

1870
00:59:02,941 --> 00:59:05,477
WE HAVE TIME FOR TWO QUESTIONS.

1871
00:59:05,477 --> 00:59:07,012
>> BEAUTIFUL TALK.

1872
00:59:07,012 --> 00:59:12,718
I THINK YOU TALKED ABOUT YOUR

1873
00:59:12,718 --> 00:59:13,685
20, 30 YEARS OF WORK HERE AND

1874
00:59:13,685 --> 00:59:14,987
I'VE BEEN FOLLOWING YOUR WORK

1875
00:59:14,987 --> 00:59:16,288
BUT I HAVE JUST TONS OF

1876
00:59:16,288 --> 00:59:16,622
QUESTIONS.

1877
00:59:16,622 --> 00:59:19,358
I'LL TALK TO YOU MORE TOMORROW.

1878
00:59:19,358 --> 00:59:24,363
BUT I'M INTRIGUED THAT IF

1879
00:59:24,363 --> 00:59:26,765
NEUROTRANSMITTER LIKE GABA OR

1880
00:59:26,765 --> 00:59:28,066
CHOLINE OR GLUTAMATE ARE

1881
00:59:28,066 --> 00:59:29,568
INITIATING THIS, THEY'RE

1882
00:59:29,568 --> 00:59:30,869
RELEASED BY ALMOST, YOU KNOW,

1883
00:59:30,869 --> 00:59:34,473
DIFFERENT KINDS OF CELLS

1884
00:59:34,473 --> 00:59:34,940
EVERYWHERE.

1885
00:59:34,940 --> 00:59:38,210
WHAT KIND OF CELLS IN THE

1886
00:59:38,210 --> 00:59:40,245
TEMPORAL REGION ARE INITIATING

1887
00:59:40,245 --> 00:59:40,479
THAT?

1888
00:59:40,479 --> 00:59:42,214
DO YOU HAVE ANY IDEA WHAT THOSE

1889
00:59:42,214 --> 00:59:42,881
CELLS ARE?

1890
00:59:42,881 --> 00:59:45,451
AND IF YOU ABLATE THEM BY, SAY,

1891
00:59:45,451 --> 00:59:46,885
LASER OR SOMETHING, OR FOR THAT

1892
00:59:46,885 --> 00:59:49,955
MATTER, IF YOU INTERRUPT THESE

1893
00:59:49,955 --> 00:59:50,856
WAVES DURING DEVELOPMENT BY SORT

1894
00:59:50,856 --> 00:59:56,562
OF POINTING SOME LASERS, WHAT

1895
00:59:56,562 --> 00:59:57,696
WILL HAPPEN TO THE DEVELOPMENT

1896
00:59:57,696 --> 00:59:58,597
OF OTHER CELL TYPES?

1897
00:59:58,597 --> 01:00:02,568
>> YEAH, SO THAT IS -- I
WAS

1898
01:00:02,568 --> 01:00:04,269
GOING TO SHOW YOU THIS ONE

1899
01:00:04,269 --> 01:00:05,304
EXPERIMENT WE DID.

1900
01:00:05,304 --> 01:00:06,271
SO ONE OF THE CELLS -- THE SLIDE

1901
01:00:06,271 --> 01:00:07,573
I SKIPPED IS THIS ONE.

1902
01:00:07,573 --> 01:00:11,376
THIS IS AN EXPERIMENT WHERE --

1903
01:00:11,376 --> 01:00:13,412
OH, IT'S NOT THIS ONE.

1904
01:00:13,412 --> 01:00:15,848
ANYWAY, MAIH CUT THE RETINA IN

1905
01:00:15,848 --> 01:00:16,648
HALF AFTER THIS EXPERIMENT.

1906
01:00:16,648 --> 01:00:18,417
SHE FOUND WHEN SHE CUT THE

1907
01:00:18,417 --> 01:00:19,518
RETINA IN HALF, THAT YOU WOULD

1908
01:00:19,518 --> 01:00:22,788
GET WAVES THAT STARTED IN THE

1909
01:00:22,788 --> 01:00:23,655
TEMPORAL PART OF THE CUT.

1910
01:00:23,655 --> 01:00:24,623
THEY WOULD ALL START HERE.

1911
01:00:24,623 --> 01:00:27,826
SO I DON'T THINK THERE'S NIS

1912
01:00:27,826 --> 01:00:29,428
SAYERLY A HOT SPOT.

1913
01:00:29,428 --> 01:00:30,629
I THINK THAT THERE IS SOMETHING

1914
01:00:30,629 --> 01:00:34,366
THAT IS EITHER SAYING DON'T

1915
01:00:34,366 --> 01:00:35,567
PROPAGATE THIS DIRECTION IF IT'S

1916
01:00:35,567 --> 01:00:37,636
GABA OR DO PROPAGATE IN THIS

1917
01:00:37,636 --> 01:00:38,370
OTHER DIRECTION.

1918
01:00:38,370 --> 01:00:39,671
SO I DON'T KNOW WHAT IT IS.

1919
01:00:39,671 --> 01:00:42,941
I WILL SAY THAT IN THE

1920
01:00:42,941 --> 01:00:44,910
ZEBRAFISH, WHERE WAVES REALLY DO

1921
01:00:44,910 --> 01:00:46,845
ALSO ALL START FROM A HOT SPOT,

1922
01:00:46,845 --> 01:00:49,314
THEY SHOWED IN THE ZEBRAFISH

1923
01:00:49,314 --> 01:00:53,085
THAT THERE ARE AN ENRICHMENT OF

1924
01:00:53,085 --> 01:00:54,419
RECEPTORS IN BIPOLAR CELLS IN

1925
01:00:54,419 --> 01:00:55,721
THAT REGION SO THEY THINK IT'S

1926
01:00:55,721 --> 01:00:57,189
JUST A LITTLE BIT MORE EXCITABLE

1927
01:00:57,189 --> 01:00:58,991
THERE, AND THAT THERE MIGHT BE A

1928
01:00:58,991 --> 01:01:00,259
GRADIENT OF SORT OF EXPRESSION

1929
01:01:00,259 --> 01:01:01,660
OF ION CHANNELS THAT MAKE THE

1930
01:01:01,660 --> 01:01:03,228
CELLS MORE EXCITABLE.

1931
01:01:03,228 --> 01:01:04,630
SO AS YOU KNOW, ACROSS

1932
01:01:04,630 --> 01:01:05,964
DEVELOPMENT, THERE'S A LOT OF

1933
01:01:05,964 --> 01:01:07,666
DEVELOPMENTAL GRADIENTS, AND IT

1934
01:01:07,666 --> 01:01:09,101
COULD JUST BE THERE'S A

1935
01:01:09,101 --> 01:01:10,168
GRADIENT -- SO THERE'S NO

1936
01:01:10,168 --> 01:01:11,336
PARTICULAR CELL TYPE, BUT THIS

1937
01:01:11,336 --> 01:01:14,940
CELL TYPE MATURES EARLIER HERE.

1938
01:01:14,940 --> 01:01:16,408
BUT THE FACT THAT -- LIKE IF YOU

1939
01:01:16,408 --> 01:01:17,376
SEE DOWN HERE THERE WAS A BUNCH

1940
01:01:17,376 --> 01:01:18,544
OF INITIATIONS HERE, BECAUSE

1941
01:01:18,544 --> 01:01:19,511
THAT WAS KIND OF THE MOST -- YOU

1942
01:01:19,511 --> 01:01:21,046
KNOW, WE CUT THE RETINA, THAT'S

1943
01:01:21,046 --> 01:01:23,015
THE MOST TEMPORAL PART OF THAT.

1944
01:01:23,015 --> 01:01:24,750
SO IT FEELS LIKE WHATEVER IT IS

1945
01:01:24,750 --> 01:01:27,152
IS A GRADIENT ACROSS THE WHOLE

1946
01:01:27,152 --> 01:01:28,687
RETINA, AND IF YOU KEPT CUTTING

1947
01:01:28,687 --> 01:01:29,888
THE RETINA, THEY WOULD JUST

1948
01:01:29,888 --> 01:01:31,323
START AT THE MOST TEMPORAL PART

1949
01:01:31,323 --> 01:01:32,057
OF THE RETINA.

1950
01:01:32,057 --> 01:01:34,793
BUT I DON'T KNOW WHY.

1951
01:01:34,793 --> 01:01:37,529
>> SO SINCE YOU DID NOT
SEE ANY

1952
01:01:37,529 --> 01:01:39,598
CHANGE WITH THE KNOCKOUT OF YOUR

1953
01:01:39,598 --> 01:01:42,968
RECEPTOR AND ALSO THE BLEUT MATE

1954
01:01:42,968 --> 01:01:45,003
AND OTHER THINGS, THERE'S A LOT

1955
01:01:45,003 --> 01:01:45,771
OF -- IN THE SYSTEM, DID YOU

1956
01:01:45,771 --> 01:01:49,408
THINK ABOUT DOING SOME DOUBLE OR

1957
01:01:49,408 --> 01:01:51,109
TRIPLE KNOCKOUTS TO SEE -- SO ON

1958
01:01:51,109 --> 01:01:53,812
ITS OWN, IT MIGHT INTERRUPT THE

1959
01:01:53,812 --> 01:01:55,280
SIGNAL TO WAVES, BUT IT MAY NOT

1960
01:01:55,280 --> 01:01:58,984
BE JUST SORT OF SUFFICIENT TO

1961
01:01:58,984 --> 01:02:00,085
TAKE CARE OF WHATEVER THOSE

1962
01:02:00,085 --> 01:02:02,688
WAVES ARE DOING.

1963
01:02:02,688 --> 01:02:04,222
>> I THINK IT'S A GOOD
QUESTION.

1964
01:02:04,222 --> 01:02:05,791
THE ONLY WORLD WE'VE GONE DOWN

1965
01:02:05,791 --> 01:02:07,626
THE DOUBLE AND TRIPLE KNOCKOUT

1966
01:02:07,626 --> 01:02:09,494
HAS BEEN FOR GAP JUNCTIONS.

1967
01:02:09,494 --> 01:02:10,662
I HAVEN'T TALKED ABOUT

1968
01:02:10,662 --> 01:02:12,497
ELECTRICAL SYNAPSES, WE TRIED TO

1969
01:02:12,497 --> 01:02:14,066
KNOCK ALL OF THEM OUT AND IT WAS

1970
01:02:14,066 --> 01:02:16,001
JUST KIND OF A NIGHTMARE.

1971
01:02:16,001 --> 01:02:19,037
AND WE HAVE NOT DONE THAT.

1972
01:02:19,037 --> 01:02:20,672
TO GET RID OF ALL OF THE

1973
01:02:20,672 --> 01:02:21,573
NEUROTRANSMITTERS WE CAN

1974
01:02:21,573 --> 01:02:22,341
BASICALLY AND SEE WHAT HAPPENS

1975
01:02:22,341 --> 01:02:24,276
AFTER THAT.

1976
01:02:24,276 --> 01:02:25,711
I MEAN, I THINK THE REASON WE

1977
01:02:25,711 --> 01:02:26,578
HAVEN'T DONE THAT IS BECAUSE

1978
01:02:26,578 --> 01:02:27,980
WE'VE BEEN REALLY FOCUSING

1979
01:02:27,980 --> 01:02:31,116
MOSTLY IN OUR LAB ON RETINAL

1980
01:02:31,116 --> 01:02:32,551
DEVELOPMENT, AND IF YOU KNOCK

1981
01:02:32,551 --> 01:02:34,586
OUT ALL THE NEUROTRANSMITTER

1982
01:02:34,586 --> 01:02:36,622
THEN THE ANIMAL CAN'T SEE SO WE

1983
01:02:36,622 --> 01:02:38,123
NOW WE CAN'T TEST WHETHER OR NOT

1984
01:02:38,123 --> 01:02:40,158
IT'S GOT DIRECTION SELECTIVITY

1985
01:02:40,158 --> 01:02:40,626
OR SOMETHING.

1986
01:02:40,626 --> 01:02:42,928
SO IT WOULD BE GOOD FOR SORT OF

1987
01:02:42,928 --> 01:02:44,129
ANATOMY EXPERIMENTS BUT NOT FOR

1988
01:02:44,129 --> 01:02:44,796
ANYTHING FUNCTIONAL AND THAT'S

1989
01:02:44,796 --> 01:02:46,865
BEEN THE TRICKY THING.

1990
01:02:46,865 --> 01:02:50,135
>> THAT WAS BEAUTIFUL.

1991
01:02:50,135 --> 01:02:53,538
I AM INTERESTED IN A BUNCH OF

1992
01:02:53,538 --> 01:02:55,474
THINGS, BUT ONE IS YOU'RE

1993
01:02:55,474 --> 01:02:57,042
SPEWING ALL THIS

1994
01:02:57,042 --> 01:02:58,243
NEUROTRANSMITTER ALL OVER THE

1995
01:02:58,243 --> 01:02:59,978
PLACE AND PRESUMABLY MOPPING IT

1996
01:02:59,978 --> 01:03:01,480
UP IS AS IMPORTANT AS SPEWING IT

1997
01:03:01,480 --> 01:03:04,216
OUT SO PRESUMABLY YOU THOUGHT A

1998
01:03:04,216 --> 01:03:05,217
LOT ABOUT THE FUNCTIONAL ROLE

1999
01:03:05,217 --> 01:03:06,451
THAT MOPPING UP MECHANISMS MAY

2000
01:03:06,451 --> 01:03:08,286
BE PLAYING AND HOW IT'S

2001
01:03:08,286 --> 01:03:08,587
ASYMMETRIC.

2002
01:03:08,587 --> 01:03:09,221
>> YEAH.

2003
01:03:09,221 --> 01:03:11,289
>> THE THING I'M SORT OF
NEAR

2004
01:03:11,289 --> 01:03:15,394
AND DEAR TO MY HEART IS HOW

2005
01:03:15,394 --> 01:03:16,461
THESE SIGNALS MIGHT BE

2006
01:03:16,461 --> 01:03:17,729
INSTRUCTIVE FOR THE CORTICAL

2007
01:03:17,729 --> 01:03:20,932
CIRCUITS OR THE CENTRAL

2008
01:03:20,932 --> 01:03:22,100
CIRCUITS.

2009
01:03:22,100 --> 01:03:26,071
DO THEY MATCH NATURAL SEEN

2010
01:03:26,071 --> 01:03:27,139
STATISTICS AND ARE THEY SORT OF

2011
01:03:27,139 --> 01:03:28,340
FOLLOWING A TRAJECTORY OF

2012
01:03:28,340 --> 01:03:29,107
DEVELOPMENT THAT ACTUALLY

2013
01:03:29,107 --> 01:03:30,842
PROVIDES SOMETHING INSTRUCTIVE

2014
01:03:30,842 --> 01:03:32,411
TO THOSE CIRCUITS SO THAT WHEN

2015
01:03:32,411 --> 01:03:36,748
YOU OPENED YOUR EYES, YOU CAN

2016
01:03:36,748 --> 01:03:39,818
SEE, AND DON'T TAKE TOO MUCH

2017
01:03:39,818 --> 01:03:42,187
LONG BECAUSE I REALLY WANT TO

2018
01:03:42,187 --> 01:03:44,356
HEAR WHAT WEY LI'S QUESTION IS.

2019
01:03:44,356 --> 01:03:47,993
>> THERE WAS A PERIOD OF
TIME

2020
01:03:47,993 --> 01:03:48,960
MAYBE 10 OR 15 YEARS AGO WHERE

2021
01:03:48,960 --> 01:03:53,231
SOME LABS DID ANALYSIS ON HOW

2022
01:03:53,231 --> 01:03:55,367
SPAISH YOE TEMPORAL PROPERTIES

2023
01:03:55,367 --> 01:03:56,868
OF RETINAL WAVES MATCHED NATURAL

2024
01:03:56,868 --> 01:03:57,269
SCENES.

2025
01:03:57,269 --> 01:03:59,504
IN A COURSE ANALYSIS, THEY'RE

2026
01:03:59,504 --> 01:04:01,073
RIGHT IN THE MIDDLE KIND OF, OF

2027
01:04:01,073 --> 01:04:02,607
WHAT IS THE VISUAL EXPERIENCE OF

2028
01:04:02,607 --> 01:04:04,710
A MOUSE.

2029
01:04:04,710 --> 01:04:05,877
I THINK THEY DIDN'T DO THE

2030
01:04:05,877 --> 01:04:07,312
VISUAL EXPERIENCE OF A MOUSE

2031
01:04:07,312 --> 01:04:08,947
WHEN THEY DID THOSE OLD

2032
01:04:08,947 --> 01:04:09,214
ANALYSES.

2033
01:04:09,214 --> 01:04:10,582
THEY DID THE VISUAL EXPERIENCE

2034
01:04:10,582 --> 01:04:11,283
OF A PRIMATE.

2035
01:04:11,283 --> 01:04:14,319
AND I THINK THAT THERE IS -- THE

2036
01:04:14,319 --> 01:04:15,954
FIELD IS RIPE, THERE ARE MANY --

2037
01:04:15,954 --> 01:04:18,990
WE HAVE GIVEN THESE MOVIES TO

2038
01:04:18,990 --> 01:04:20,092
MANY DIFFERENT COMPUTATIONAL

2039
01:04:20,092 --> 01:04:20,859
LABS AT THIS POINT.

2040
01:04:20,859 --> 01:04:22,060
THERE CERTAINLY ARE A LOT OF

2041
01:04:22,060 --> 01:04:25,230
LABS THAT HAVE USED THESE AS

2042
01:04:25,230 --> 01:04:26,631
RUNNING SIMULATIONS THAT THEY

2043
01:04:26,631 --> 01:04:28,934
HAVE ON DEVELOPMENT OF VISUAL

2044
01:04:28,934 --> 01:04:30,335
CORTICAL CIRCUITS AND SO THERE

2045
01:04:30,335 --> 01:04:33,872
HAS BEEN A LOT OF WORK THAT'S

2046
01:04:33,872 --> 01:04:35,040
BEEN DONE IN THAT ARENA.

2047
01:04:35,040 --> 01:04:36,775
I'D BE CURIOUS TO THINK IF YOU

2048
01:04:36,775 --> 01:04:38,410
THOUGHT ANY OF IT WAS MEANINGFUL

2049
01:04:38,410 --> 01:04:40,946
OR NOT.

2050
01:04:40,946 --> 01:04:42,481
IN THE CORTICAL CIRCUIT REGIME,

2051
01:04:42,481 --> 01:04:44,983
ONE OF I THINK THE REALLY

2052
01:04:44,983 --> 01:04:46,918
INTERESTING AREAS WHICH YOU WILL

2053
01:04:46,918 --> 01:04:48,120
FIND NOT INTERESTING AT ALL IS

2054
01:04:48,120 --> 01:04:50,989
THAT IT TURNS OUT CORTICAL

2055
01:04:50,989 --> 01:04:52,290
INHIBITORY INTERNEURONS UNDERGO

2056
01:04:52,290 --> 01:04:53,692
A LOT OF CELL DEATH AND IT TURNS

2057
01:04:53,692 --> 01:04:55,127
OUT THE FREQUENCY WITH WHICH

2058
01:04:55,127 --> 01:04:56,862
THEY PARTICIPATE IN THESE

2059
01:04:56,862 --> 01:04:58,396
WAVE-DRIVEN EVENTUALLY

2060
01:04:58,396 --> 01:04:59,931
INFLUENCES HOW MANY CORTICAL

2061
01:04:59,931 --> 01:05:02,067
INHIBITORY INTERNEURONS SURVIVE.

2062
01:05:02,067 --> 01:05:03,735
SO THAT'S IMPORTANT FOR SHAPING

2063
01:05:03,735 --> 01:05:04,770
LOCAL CIRCUITS WITHIN CORTEX,

2064
01:05:04,770 --> 01:05:06,338
WHAT THAT MEANS ABOUT NATURAL

2065
01:05:06,338 --> 01:05:07,739
SCENES, I THINK NOW IS THE TIME

2066
01:05:07,739 --> 01:05:08,974
TO DO THAT BECAUSE I THINK WE

2067
01:05:08,974 --> 01:05:10,375
HAVE A LOT MORE INFORMATION TO

2068
01:05:10,375 --> 01:05:11,042
CHECK THAT OUT.

2069
01:05:11,042 --> 01:05:12,778
SO I WOULD LOVE TO TALK MORE

2070
01:05:12,778 --> 01:05:15,947
ABOUT THAT.

2071
01:05:15,947 --> 01:05:16,114
WEI.

2072
01:05:16,114 --> 01:05:17,582
>> MARLA, GREAT TALK.

2073
01:05:17,582 --> 01:05:17,849
BEAUTIFUL.

2074
01:05:17,849 --> 01:05:18,116
>> THANKS.

2075
01:05:18,116 --> 01:05:19,351
>> I PROBABLY SHOULD KNOW
THE

2076
01:05:19,351 --> 01:05:20,952
ANSWER, BUT IN YOUR BETA

2077
01:05:20,952 --> 01:05:23,722
2 KNOCKOUT WHERE YOU LOST

2078
01:05:23,722 --> 01:05:29,060
HORIZONTAL PREFERRED DSL, THEY

2079
01:05:29,060 --> 01:05:31,563
DIDN'T LOSE THE CELLS BUT THEY

2080
01:05:31,563 --> 01:05:32,430
LOST DIRECTION SELECTIVITY.

2081
01:05:32,430 --> 01:05:32,764
>> RIGHT.

2082
01:05:32,764 --> 01:05:34,065
>> SO DO YOU THINK THE
WAVE HAS

2083
01:05:34,065 --> 01:05:35,600
SOMETHING TO DO WITH THE SETTING

2084
01:05:35,600 --> 01:05:39,304
UP THIS VERY ASYMMETRIC

2085
01:05:39,304 --> 01:05:41,206
CONNECTION BETWEEN STARBURST AND

2086
01:05:41,206 --> 01:05:41,373
DSL?

2087
01:05:41,373 --> 01:05:44,776
>> SO WE HAVE A WHOLE TALK
ON

2088
01:05:44,776 --> 01:05:46,411
THAT WHICH I DID NOT GIVE, BUT

2089
01:05:46,411 --> 01:05:48,046
I'M HAPPY TO GIVE NOW.

2090
01:05:48,046 --> 01:05:50,015
JUST KIDDING.

2091
01:05:50,015 --> 01:05:52,217
SO YES, SO WE'RE WORKING ON

2092
01:05:52,217 --> 01:05:52,417
THAT.

2093
01:05:52,417 --> 01:05:54,186
SO IT IS -- SO THEY DO -- SO THE

2094
01:05:54,186 --> 01:05:54,953
CELLS DID NOT DIE.

2095
01:05:54,953 --> 01:05:57,122
THEY ARE EQUALLY RESPONSIVE TO

2096
01:05:57,122 --> 01:05:59,624
LIGHT MOVING IN ANY DIRECTION.

2097
01:05:59,624 --> 01:06:01,560
THEY RECEIVE LESS INHIBITION

2098
01:06:01,560 --> 01:06:03,795
FROM THE STARBURST CELL WHEN

2099
01:06:03,795 --> 01:06:05,931
THEY MOVE IN THE NULL DIRECTION,

2100
01:06:05,931 --> 01:06:07,599
WHICH IS SORT OF WHAT GAVE THEM

2101
01:06:07,599 --> 01:06:09,134
THEIR DIRECTION SELECTIVITY.

2102
01:06:09,134 --> 01:06:11,102
IT SEEMS LIKE THE STARBURST CELL

2103
01:06:11,102 --> 01:06:12,737
ITSELF HAS NOT LOST ITS ABILITY

2104
01:06:12,737 --> 01:06:16,341
TO RELEASE GABA IN THE BETA

2105
01:06:16,341 --> 01:06:18,410
2 KNOCKOUT BUT RATHER WE THINK

2106
01:06:18,410 --> 01:06:22,247
IT'S THE WIRING OF THE A STARBUT

2107
01:06:22,247 --> 01:06:25,183
CELLS TO THE DIRECT SELECTIVE

2108
01:06:25,183 --> 01:06:27,686
GANGLION CELLS, WE DID SINGLE

2109
01:06:27,686 --> 01:06:29,921
CELL RNA SEQ, WE KNOW WHICH ARE

2110
01:06:29,921 --> 01:06:30,856
THE HORIZONTAL, WHICH ARE THE

2111
01:06:30,856 --> 01:06:31,289
VERTICAL.

2112
01:06:31,289 --> 01:06:33,024
WHAT GOT LOST IN THE BETA

2113
01:06:33,024 --> 01:06:33,959
2 KNOCKOUT, WE LOOKED RIGHT AT

2114
01:06:33,959 --> 01:06:35,093
THE AGE WHEN WIRING IS HAPPENING

2115
01:06:35,093 --> 01:06:36,628
AND WE FOUND NOTHING.

2116
01:06:36,628 --> 01:06:39,231
NOTHING.

2117
01:06:39,231 --> 01:06:42,334
SO I DON'T THINK THAT'S

2118
01:06:42,334 --> 01:06:44,002
REGULATED AT A TRANSCRIPTIONAL

2119
01:06:44,002 --> 01:06:45,237
LEVEL AND WE'RE LOOKING AT

2120
01:06:45,237 --> 01:06:45,904
PROTEOMICS NOW.

2121
01:06:45,904 --> 01:06:46,805
>> THAT'S INTERESTING
BECAUSE

2122
01:06:46,805 --> 01:06:48,406
YOU'RE VERTICAL IS STILL THERE,

2123
01:06:48,406 --> 01:06:49,608
SO ASYMMETRIC WIRING STILL

2124
01:06:49,608 --> 01:06:51,543
HAPPENS IN THOSE VERTICAL ONES.

2125
01:06:51,543 --> 01:06:54,512
>> YEAH, BUT I WILL SAY, I
WAS

2126
01:06:54,512 --> 01:06:56,715
AT A MEETING WHICH I CAN'T

2127
01:06:56,715 --> 01:06:57,716
REMEMBER WHERE, WHERE I WAS

2128
01:06:57,716 --> 01:07:01,553
TOLD, AND THERE ARE OPTOMETRISTS

2129
01:07:01,553 --> 01:07:02,621
AND OPHTHALMOLOGISTS HERE WHO

2130
01:07:02,621 --> 01:07:03,488
CAN ANSWER THIS QUESTION.

2131
01:07:03,488 --> 01:07:05,257
SO IT TURNS OUT FOR HUMANS,

2132
01:07:05,257 --> 01:07:07,325
THERE ARE A LOT OF HUMAN GENETIC

2133
01:07:07,325 --> 01:07:09,828
DISORDERS WHERE THEY HAVE

2134
01:07:09,828 --> 01:07:13,198
NYSTAGMUS, AND ONE OF THOSE IS

2135
01:07:13,198 --> 01:07:18,670
THIS FMR -- FMRD7, THAT ACTUALLY

2136
01:07:18,670 --> 01:07:20,405
LEADS TO NYSTAGMUS, AND THIS

2137
01:07:20,405 --> 01:07:21,840
OPHTHALMOLOGIST I WAS TALKING TO

2138
01:07:21,840 --> 01:07:23,808
AT THIS MEETING TOLD ME THAT

2139
01:07:23,808 --> 01:07:25,343
WHEN HUMAN PATIENTS COME IN AND

2140
01:07:25,343 --> 01:07:28,813
THEY HAVE HORIZONTAL

2141
01:07:28,813 --> 01:07:30,015
OPTONYSTAGMUS, THEY THINK

2142
01:07:30,015 --> 01:07:30,982
THERE'S A GENETIC DEFICIT, IT

2143
01:07:30,982 --> 01:07:32,417
COULD BE IN THE RET KA, IT COULD

2144
01:07:32,417 --> 01:07:34,953
BE ELSEWHERE, BUT IF THEY HAVE

2145
01:07:34,953 --> 01:07:36,021
VERTICAL NYSTAGMUS, IT'S AN

2146
01:07:36,021 --> 01:07:37,589
INJURY TO THE BRAINSTEM.

2147
01:07:37,589 --> 01:07:40,392
THERE'S SOMETHING DIFFERENT

2148
01:07:40,392 --> 01:07:46,965
ABOUT THE OPTOKINETIC REFLEX --

2149
01:07:46,965 --> 01:07:48,934
NYSTAGMUS IN HORIZONTAL VERSUS

2150
01:07:48,934 --> 01:07:49,567
VERTICAL.

2151
01:07:49,567 --> 01:07:51,202
THOSE ARE DIFFERENT AXES EVEN

2152
01:07:51,202 --> 01:07:52,637
FOR REFLEXIVE EYE MOVEMENTS.

2153
01:07:52,637 --> 01:07:54,272
FOR THE MOUSE, THEY TRACK MUCH

2154
01:07:54,272 --> 01:07:55,607
MORE RELIABLY HORIZONTALLY THAN

2155
01:07:55,607 --> 01:07:58,343
THEY DO VERTICALLY, AND SO THEY

2156
01:07:58,343 --> 01:07:59,644
ARE DIFFERENT, RIGHT, AND SO I

2157
01:07:59,644 --> 01:08:01,346
DON'T KNOW IF SOMEONE -- SO WHY

2158
01:08:01,346 --> 01:08:04,783
ONE MIGHT BE MORE SUSCEPTIBLE TO

2159
01:08:04,783 --> 01:08:05,784
EXPERIENCE LIKE WAVES AND THE

2160
01:08:05,784 --> 01:08:06,651
OTHER ONE NOT, I DON'T KNOW.

2161
01:08:06,651 --> 01:08:09,587
>> SO THE VERTICAL ONE,
THE DS

2162
01:08:09,587 --> 01:08:11,456
IS ALSO ESTABLISHED BEFORE EYE

2163
01:08:11,456 --> 01:08:11,690
OPENING?

2164
01:08:11,690 --> 01:08:13,291
>> YEAH.

2165
01:08:13,291 --> 01:08:15,627
>> THAT KILLS MY THEORY
THAT

2166
01:08:15,627 --> 01:08:17,228
MAYBE BLINKING GIVES YOU A

2167
01:08:17,228 --> 01:08:17,896
NATURAL SORT OF DIRECTION.

2168
01:08:17,896 --> 01:08:19,764
>> OH, MY GOD, I LOVE
THAT.

2169
01:08:19,764 --> 01:08:21,499
NO, IT'S THERE BEFORE EYE

2170
01:08:21,499 --> 01:08:21,733
OPENING.

2171
01:08:21,733 --> 01:08:22,067
>> THANK YOU.

2172
01:08:22,067 --> 01:08:22,801
>> HI.

2173
01:08:22,801 --> 01:08:24,269
>> FANTASTIC TALK.

2174
01:08:24,269 --> 01:08:26,438
I'M INTERESTED IN THE

2175
01:08:26,438 --> 01:08:27,672
ANGIOGENESIS PART AND I ALSO

2176
01:08:27,672 --> 01:08:29,708
THINK FROM THE PERSPECTIVE OF

2177
01:08:29,708 --> 01:08:30,275
NEUROMETABOLISM.

2178
01:08:30,275 --> 01:08:33,111
SO YOU SHOWED THAT EARLY ON P7,

2179
01:08:33,111 --> 01:08:34,646
SOME OF THE PERIPHERAL BLOOD

2180
01:08:34,646 --> 01:08:35,747
VESSELS AREN'T THERE YET.

2181
01:08:35,747 --> 01:08:38,483
DO YOU SEE WAVES IN AREAS WHERE

2182
01:08:38,483 --> 01:08:39,684
THERE'S NO VASCULATURE?

2183
01:08:39,684 --> 01:08:40,986
SO YOU SHOWED THAT THE WAVES

2184
01:08:40,986 --> 01:08:43,188
AREN'T REALLY IMPORTANT FOR

2185
01:08:43,188 --> 01:08:45,156
ANGIOGENESIS, BUT IS

2186
01:08:45,156 --> 01:08:45,824
ANGIOGENESIS IMPORTANT FOR THE

2187
01:08:45,824 --> 01:08:47,058
WAVES?

2188
01:08:47,058 --> 01:08:48,193
SIMILARLY, THE GLIAL CELLS WHICH

2189
01:08:48,193 --> 01:08:50,929
WE KNOW ARE INVOLVED IN ENERGY

2190
01:08:50,929 --> 01:08:52,797
METABOLISM FOR THE NEURONS, IS

2191
01:08:52,797 --> 01:08:54,366
THAT IMPORTANT?

2192
01:08:54,366 --> 01:08:57,402
>> YEAH, SO WE HAVEN'T
SEEN

2193
01:08:57,402 --> 01:08:58,937
THAT, THERE WAS A RETINA

2194
01:08:58,937 --> 01:09:01,439
CONFERENCE WHERE EVELYN

2195
01:09:01,439 --> 01:09:03,008
CERNIGORE ACTUALLY MADE THE CASE

2196
01:09:03,008 --> 01:09:04,843
THAT SHE THOUGHT CONERGIC WAVES

2197
01:09:04,843 --> 01:09:09,114
INITIATED FROM THE LEADI LEADINE

2198
01:09:09,114 --> 01:09:13,251
OF THE PRIF  PERIPHERAL VASCULA.

2199
01:09:13,251 --> 01:09:14,219
WE HAVE NOT SEEN THAT BUT

2200
01:09:14,219 --> 01:09:15,887
HAVEN'T EXACTLY LOOKED FOR IT

2201
01:09:15,887 --> 01:09:17,722
AND SHE MADE THE CASE SHE

2202
01:09:17,722 --> 01:09:19,591
THOUGHT THAT WAS KIND OF A

2203
01:09:19,591 --> 01:09:20,125
METABOLISM ARGUMENT.

2204
01:09:20,125 --> 01:09:22,093
AND THAT IS A SUPER INTERESTING

2205
01:09:22,093 --> 01:09:22,660
QUESTION.

2206
01:09:22,660 --> 01:09:23,862
HOW DO WE TEST THAT?

2207
01:09:23,862 --> 01:09:25,730
I WOULD REALLY -- INSTEAD OF

2208
01:09:25,730 --> 01:09:26,831
THIS CORRELATION, HOW WOULD WE

2209
01:09:26,831 --> 01:09:27,365
TEST IT?

2210
01:09:27,365 --> 01:09:27,899
I LOVE THIS.

2211
01:09:27,899 --> 01:09:30,201
>> I DID MY PH.D. IN GARY

2212
01:09:30,201 --> 01:09:31,603
ELLEN'S LAB AND THERE'S A WHOLE

2213
01:09:31,603 --> 01:09:34,572
SLEW OF BEAUTIFUL

2214
01:09:34,572 --> 01:09:35,273
NEUROMETABOLISM BIOSENSORS SO

2215
01:09:35,273 --> 01:09:38,176
THAT WOULD BE ONE WAY, IS USE

2216
01:09:38,176 --> 01:09:39,377
OTHER BIOSENSORS THAT MIGHT GIVE

2217
01:09:39,377 --> 01:09:40,812
YOU A CLUE AS TO WHERE THE

2218
01:09:40,812 --> 01:09:41,446
STARTER AREAS ARE.

2219
01:09:41,446 --> 01:09:42,680
>> THAT IS A GREAT IDEA.

2220
01:09:42,680 --> 01:09:44,549
THANK YOU.

2221
01:09:44,549 --> 01:09:46,751
>> SURE.

2222
01:09:46,751 --> 01:09:47,285
>> HI.

2223
01:09:47,285 --> 01:09:48,820
IT WAS A BEAUTIFUL TALK, AND I

2224
01:09:48,820 --> 01:09:51,790
DID MY GRADUATE WORK THE A

2225
01:09:51,790 --> 01:09:57,362
BERKELEY, CHA CARLA SCHATZ ALWAS

2226
01:09:57,362 --> 01:09:59,431
WOULD TALK ABOUT YOUR RETINAL

2227
01:09:59,431 --> 01:10:00,298
WAVE WORK.

2228
01:10:00,298 --> 01:10:01,933
I WAS ALWAYS INTRIGUED BY THE

2229
01:10:01,933 --> 01:10:03,134
HYPOTHESIS THAT RETINAL WAVES

2230
01:10:03,134 --> 01:10:05,003
ARE INVOLVED IN THE DEVELOPMENT

2231
01:10:05,003 --> 01:10:09,040
OF PATTERNING AND YOU TALKED

2232
01:10:09,040 --> 01:10:10,041
ABOUT HOW DIFFERENT FEATURES OF

2233
01:10:10,041 --> 01:10:13,311
THE WAVES COULD BE INVOLVED IN

2234
01:10:13,311 --> 01:10:14,846
RETINOTOPY AND OCULAR DOMINANCE.

2235
01:10:14,846 --> 01:10:16,481
YOU MENTIONED A LITTLE ABOUT HOW

2236
01:10:16,481 --> 01:10:17,182
SOMETIMES THERE'S LIGHT COMING

2237
01:10:17,182 --> 01:10:19,317
IN BEFORE THE EYE OPENS, YOU'RE

2238
01:10:19,317 --> 01:10:20,752
GETTING SOME VISUAL INFORMATION

2239
01:10:20,752 --> 01:10:26,991
EVEN BEFORE EYE OPENING BUT I

2240
01:10:26,991 --> 01:10:30,929
GUESS HOW STEREOTYPICAL IS THE

2241
01:10:30,929 --> 01:10:32,330
RETINOTOPY FROM ONE ANIMAL TO

2242
01:10:32,330 --> 01:10:32,764
ANOTHER?

2243
01:10:32,764 --> 01:10:34,432
IS THE PATTERNING ENOUGH TO

2244
01:10:34,432 --> 01:10:35,633
AFFECT THE ANATOMY THAT YOU

2245
01:10:35,633 --> 01:10:36,701
COULD SAY THIS IS FROM THIS PART

2246
01:10:36,701 --> 01:10:38,570
OF THE RETINA VERSUS ANOTHER

2247
01:10:38,570 --> 01:10:41,206
PART, AND IF YOU WERE TO REAR

2248
01:10:41,206 --> 01:10:42,507
ANIMALS, I GUESS KIND OF A

2249
01:10:42,507 --> 01:10:45,877
BINDING QUESTION, AT SOME POINT

2250
01:10:45,877 --> 01:10:49,514
YOU HAVE SOME BILATERAL CELLS IN

2251
01:10:49,514 --> 01:10:52,350
THE COLLICULUS AND IN THE CORTEX

2252
01:10:52,350 --> 01:10:53,485
THAT HAVE INFORMATION IN BOTH

2253
01:10:53,485 --> 01:10:54,752
EYES AND THEY HAVE TO BE -- THEY

2254
01:10:54,752 --> 01:10:57,722
HAVE TO MATCH FOR THEIR INPUT,

2255
01:10:57,722 --> 01:11:00,792
IF YOU WERE TO REAR THE PUPS IN

2256
01:11:00,792 --> 01:11:02,427
PURE DARKNESS, DO THEY STILL

2257
01:11:02,427 --> 01:11:04,062
HAVE -- IS THERE ANY BINDING

2258
01:11:04,062 --> 01:11:05,130
ISSUES BETWEEN THE TWO EYES?

2259
01:11:05,130 --> 01:11:06,798
>> THAT'S A GOOD QUESTION.

2260
01:11:06,798 --> 01:11:09,000
I DON'T THINK I CAN ANSWER THE

2261
01:11:09,000 --> 01:11:09,567
LAST ONE.

2262
01:11:09,567 --> 01:11:10,401
IT'S BEEN DONE AND I DON'T KNOW

2263
01:11:10,401 --> 01:11:16,307
WHAT THE ANSWER IS.

2264
01:11:16,307 --> 01:11:18,109
KNOW J.C. KING HAS DONE THAT IN

2265
01:11:18,109 --> 01:11:20,378
THE COLLICULUS AND FOUND -- I

2266
01:11:20,378 --> 01:11:22,247
CAN'T REMEMBER -- BINDING

2267
01:11:22,247 --> 01:11:23,648
BETWEEN ORIENTATION SELECTIVE

2268
01:11:23,648 --> 01:11:24,516
CELLS, THERE WAS LIKE SOMETHING

2269
01:11:24,516 --> 01:11:27,152
HE FOUND, THERE WAS SOME FEATURE

2270
01:11:27,152 --> 01:11:28,486
THAT WAS INITIALLY ESTABLISHED

2271
01:11:28,486 --> 01:11:30,955
SO IN THE BETA 2 KNOCKOUT, IT

2272
01:11:30,955 --> 01:11:34,959
WAS LACKING, AND THEN NEVER

2273
01:11:34,959 --> 01:11:36,828
COULD GET THE TWO TO ALIGN SORT

2274
01:11:36,828 --> 01:11:38,463
OF WHEN THE EYES WERE OPEN, AND

2275
01:11:38,463 --> 01:11:40,965
I DON'T REMEMBER WHAT THAT

2276
01:11:40,965 --> 01:11:44,035
PARTICULAR FEATURE WAS.

2277
01:11:44,035 --> 01:11:46,871
THE RETINOTOPY IS EXTREMELY WELL

2278
01:11:46,871 --> 01:11:48,206
STEREOTYPED, I WOULD SAY, SO YOU

2279
01:11:48,206 --> 01:11:49,841
CAN SAY, YOU KNOW, IF YOU HAVE A

2280
01:11:49,841 --> 01:11:51,943
DEFICIT IN THIS PART OF THE

2281
01:11:51,943 --> 01:11:52,877
COLLICULUS, YOU KNOW WHAT PART

2282
01:11:52,877 --> 01:11:54,679
OF THE RETINA THAT DEFICIT HAS

2283
01:11:54,679 --> 01:11:55,446
EMERGED FROM.

2284
01:11:55,446 --> 01:11:58,983
SO THAT ANSWERS THAT QUESTION.

2285
01:11:58,983 --> 01:12:00,518
>> THAT COMES PURELY FROM
THE

2286
01:12:00,518 --> 01:12:00,919
RETINAL WAVES?

2287
01:12:00,919 --> 01:12:03,221
>> NO, THERE DEFINITELY
ARE

2288
01:12:03,221 --> 01:12:05,089
MOLECULAR GRADIENTS THAT HAVE

2289
01:12:05,089 --> 01:12:05,623
ESTABLISHED THAT.

2290
01:12:05,623 --> 01:12:06,958
IT'S ACTUALLY ANOTHER THING

2291
01:12:06,958 --> 01:12:10,328
THAT'S UNIQUE ABOUT THE

2292
01:12:10,328 --> 01:12:12,297
HORIZONTAL AXIS VERSUS THE

2293
01:12:12,297 --> 01:12:15,166
VERTICAL AXIS, SO THERE'S A VERY

2294
01:12:15,166 --> 01:12:17,468
FAMOUS -- IN TEXTBOOKS YOU LEARN

2295
01:12:17,468 --> 01:12:19,771
ABOUT FRNA AND FA, SO THERE'S

2296
01:12:19,771 --> 01:12:21,072
ONE GRADIENT IN THE RETINA,

2297
01:12:21,072 --> 01:12:23,474
THERE'S ANOTHER GRADIENT IN THE

2298
01:12:23,474 --> 01:12:24,042
TECTUM.

2299
01:12:24,042 --> 01:12:26,044
IT'S A REPULSIVE INTERACTION,

2300
01:12:26,044 --> 01:12:28,413
AND EXACTLY WHERE A PARTICULAR

2301
01:12:28,413 --> 01:12:30,181
RETINAL GANGLION CELL ENDS UP

2302
01:12:30,181 --> 01:12:31,616
SORT OF DEPENDS ON WHERE YOU

2303
01:12:31,616 --> 01:12:33,117
HAVE THAT -- WHERE THE REPULSION

2304
01:12:33,117 --> 01:12:34,686
IS MINIMAL BETWEEN THOSE TWO,

2305
01:12:34,686 --> 01:12:35,853
BUT THAT ONLY WORKS ON THE

2306
01:12:35,853 --> 01:12:36,154
HOARDS ONE.

2307
01:12:36,154 --> 01:12:39,958
SO THE VERTICAL ONE, WHICH IS

2308
01:12:39,958 --> 01:12:41,226
MEDIAL LATERAL ON THE

2309
01:12:41,226 --> 01:12:42,193
COLLICULUS, DOES NOT WORK THAT

2310
01:12:42,193 --> 01:12:42,627
WAY.

2311
01:12:42,627 --> 01:12:44,963
IT'S FBs BUT IT'S NOT A

2312
01:12:44,963 --> 01:12:46,030
GRADIENT AND THERE'S SOME SORT

2313
01:12:46,030 --> 01:12:47,465
OF SORTING THAT'S THOUGHT TO

2314
01:12:47,465 --> 01:12:49,100
HAPPEN IN THE OPTIC TRACK SO

2315
01:12:49,100 --> 01:12:50,301
THAT EVERYTHING GROWS IN THE

2316
01:12:50,301 --> 01:12:51,402
RIGHT PLACE, AND THEN THERE'S

2317
01:12:51,402 --> 01:12:52,604
KIND OF A REFINEMENT ONCE YOU

2318
01:12:52,604 --> 01:12:53,071
GET THERE.

2319
01:12:53,071 --> 01:12:53,871
SO THAT'S A LITTLE BIT

2320
01:12:53,871 --> 01:12:54,439
DIFFERENT.

2321
01:12:54,439 --> 01:12:57,542
BUT ALONG THE NASAL TEMPORAL

2322
01:12:57,542 --> 01:12:59,444
AXIS RETINA ANTERIOR POSTERIOR

2323
01:12:59,444 --> 01:13:01,512
AND THE TECTUM, THAT SEEMS TO BE

2324
01:13:01,512 --> 01:13:02,513
WELL-DEFINED BY WHERE YOU ARE IN

2325
01:13:02,513 --> 01:13:03,514
THE RETINA.

2326
01:13:03,514 --> 01:13:07,452
I DID WANT TO MENTION ONE THING

2327
01:13:07,452 --> 01:13:09,320
WHERE THIS IS AN IDEA FROM HOLLY

2328
01:13:09,320 --> 01:13:11,155
KLEIN'S LAB THAT PROPAGATION

2329
01:13:11,155 --> 01:13:13,057
BIAS MIGHT BE IMPORTANT FOR

2330
01:13:13,057 --> 01:13:16,628
RETINOTOPY AND SHE DID THESE

2331
01:13:16,628 --> 01:13:23,534
SPARE MENTZ IN XENIPUS, SHE DID

2332
01:13:23,534 --> 01:13:25,837
EXPERIMENTS WHERE SHE TOOK A

2333
01:13:25,837 --> 01:13:27,705
XENIPUS AND SHE FORCED TO HAVE

2334
01:13:27,705 --> 01:13:30,108
REVERSE OPTIC FLOW SO SHE KEPT

2335
01:13:30,108 --> 01:13:33,177
IT IN AGAR AND THE RETINOTOPIC

2336
01:13:33,177 --> 01:13:34,712
MAPS GOT MESSED UP SO SHE ARGUED

2337
01:13:34,712 --> 01:13:36,481
THAT THERE IS AN ACTIVITY,

2338
01:13:36,481 --> 01:13:39,651
SOMETHING LIKE -- THE RETINAL

2339
01:13:39,651 --> 01:13:41,152
WAVE VISION REPRAYSMENT ACTUALLY

2340
01:13:41,152 --> 01:13:43,354
DOES SET UP RETINOTOPY IN THAT

2341
01:13:43,354 --> 01:13:43,554
CASE.

2342
01:13:43,554 --> 01:13:45,256
SO IT'S NOT TOTALLY MESSED UP,

2343
01:13:45,256 --> 01:13:46,557
IT'S JUST -- IT HASN'T REFINED

2344
01:13:46,557 --> 01:13:56,868
AS MUCH AS OTHERS.

2345
01:13:59,337 --> 01:14:00,405
>> THANK YOU.

2346
01:14:00,405 --> 01:14:10,581
[APPLAUSE]

2347
01:14:12,917 --> 01:14:15,353
>> THANK YOU FOR
MODERATING THIS

2348
01:14:15,353 --> 01:14:15,820
Q & A.

2349
01:14:15,820 --> 01:14:18,122
MY JOB IS TO CLOSE US OUT AND TO

2350
01:14:18,122 --> 01:14:19,857
GET EVERYONE TO THE POST LECTURE

2351
01:14:19,857 --> 01:14:20,625
RECEPTION OUTSIDE.

2352
01:14:20,625 --> 01:14:21,993
BUT THERE'S MANY PEOPLE WHO I

2353
01:14:21,993 --> 01:14:23,728
REALLY WANT TO THANK HERE.

2354
01:14:23,728 --> 01:14:26,130
FOR MAKING TODAY HAPPEN.

2355
01:14:26,130 --> 01:14:29,400
OUR FOLKS AT THE NEI, WHO HELPED

2356
01:14:29,400 --> 01:14:31,269
COORDINATE THIS, JOE AND YOUR

2357
01:14:31,269 --> 01:14:33,771
CREW AT THE FNIH, THANKS TO YOUR

2358
01:14:33,771 --> 01:14:37,175
TEAM FOR WORKING WITH US.

2359
01:14:37,175 --> 01:14:38,643
AND OBVIOUSLY MOST OF ALL,

2360
01:14:38,643 --> 01:14:39,610
MARLA, THANK YOU TO YOU FOR

2361
01:14:39,610 --> 01:14:42,313
COMING HERE AND SHARING YOUR

2362
01:14:42,313 --> 01:14:43,881
SORT OF EXPERTISE WITH US.

2363
01:14:43,881 --> 01:14:45,516
THERE ARE SO MANY DIFFERENT

2364
01:14:45,516 --> 01:14:47,185
THINGS ABOUT LECTURE THAT I

2365
01:14:47,185 --> 01:14:48,286
REALLY LOVED.

2366
01:14:48,286 --> 01:14:49,921
WE USE THE PHRASE

2367
01:14:49,921 --> 01:14:52,924
INTERDISCIPLINARY COLLABORATION

2368
01:14:52,924 --> 01:14:54,292
IN THE BEGINNING, AND I LOVE

2369
01:14:54,292 --> 01:15:01,833
THAT YOU WEAVED IN SORT OF

2370
01:15:01,833 --> 01:15:03,234
NEUROSCIENCE, ELECTROPHYSIOLOGY,

2371
01:15:03,234 --> 01:15:05,103
ANATOMY, ALL INTO THIS.

2372
01:15:05,103 --> 01:15:07,205
AND I DIDN'T REALIZE YOU WERE A

2373
01:15:07,205 --> 01:15:09,073
PHYSICIST BY BACKGROUND, AND I

2374
01:15:09,073 --> 01:15:10,608
THINK THAT CAME THROUGH, THAT

2375
01:15:10,608 --> 01:15:12,577
YOU APPROACH THESE PROBLEMS WITH

2376
01:15:12,577 --> 01:15:16,714
THE MIND OF A PHYSICIST.

2377
01:15:16,714 --> 01:15:21,219
AND I SORT OF LOVED FROM A

2378
01:15:21,219 --> 01:15:22,387
PERSONAL PERSPECTIVE -- WELL,

2379
01:15:22,387 --> 01:15:24,288
OART THING IS I ACTUALLY LOVED

2380
01:15:24,288 --> 01:15:25,256
LISTENING TO THE Q & A.

2381
01:15:25,256 --> 01:15:28,259
IF THERE ARE TRAINEES HERE, YOU

2382
01:15:28,259 --> 01:15:28,926
MIGHT JUST CONSIDER THINKING

2383
01:15:28,926 --> 01:15:30,528
ABOUT THAT, AND MAYBE EVEN

2384
01:15:30,528 --> 01:15:31,929
WATCHING THE VIDEOCAST, BECAUSE

2385
01:15:31,929 --> 01:15:34,766
I THOUGHT THAT WAS A GREAT

2386
01:15:34,766 --> 01:15:36,100
EXAMPLE OF HOW WE CAN ALL LEARN

2387
01:15:36,100 --> 01:15:38,503
HOW TO MANAGE A Q & A
SECTION

2388
01:15:38,503 --> 01:15:40,037
AND HOW IT CAN GENERATE SORT OF

2389
01:15:40,037 --> 01:15:40,605
NEW IDEAS.

2390
01:15:40,605 --> 01:15:41,739
I THOUGHT THAT WAS FASCINATING

2391
01:15:41,739 --> 01:15:43,574
TO LISTEN TO AND JUST -- YOU

2392
01:15:43,574 --> 01:15:45,643
MIGHT JUST CONSIDER THAT AND

2393
01:15:45,643 --> 01:15:46,644
THINK ABOUT THAT A LITTLE BIT.

2394
01:15:46,644 --> 01:15:48,613
AND JUST FROM A PERSONAL

2395
01:15:48,613 --> 01:15:49,480
PERSPECTIVE, AS A MEDICAL

2396
01:15:49,480 --> 01:15:51,048
STUDENT, I ONCE WORKED IN THE

2397
01:15:51,048 --> 01:15:53,050
LAB THAT STUDIED THE STARBURST

2398
01:15:53,050 --> 01:15:54,485
AM KRON CELL AND IT WAS GREAT TO

2399
01:15:54,485 --> 01:15:56,888
SEE IT LIKE 30 YEARS LATER UP ON

2400
01:15:56,888 --> 01:15:58,389
THE SCREEN HERE.

2401
01:15:58,389 --> 01:15:59,724
SO JUST THANK YOU FOR SHARING

2402
01:15:59,724 --> 01:16:02,794
ALL OF THAT WITH US.

2403
01:16:02,794 --> 01:16:07,799
AND SO JOE, ENRIQUE, MARLA, AND

2404
01:16:07,799 --> 01:16:08,599
OUR LEADERSHIP TEAM, IF YOU

2405
01:16:08,599 --> 01:16:09,867
COULD STAY WITH US JUST TO TAKE

2406
01:16:09,867 --> 01:16:11,302
A FEW PHOTOS WITH DUSTIN

2407
01:16:11,302 --> 01:16:13,070
AFTERWARDS, BUT TO THE REST OF

2408
01:16:13,070 --> 01:16:14,272
YOU, THERE'S A RECEPTION OUTSIDE

2409
01:16:14,272 --> 01:16:15,740
AND IF YOU COULD JUST PLEASE

2410
01:16:15,740 --> 01:16:16,974
SORT OF TAKE A MINUTE, INTRODUCE

2411
01:16:16,974 --> 01:16:18,109
YOURSELF TO DR. FELLER IF YOU

2412
01:16:18,109 --> 01:16:21,412
HAVEN'T MET HER AND JUST ENJOY

2413
01:16:21,412 --> 01:16:21,813
THE RECEPTION.

2414
01:16:21,813 --> 01:16:22,113
THANK YOU.

2415
01:16:22,113 --> 01:16:25,550
[APPLAUSE]