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   >> OKAY. WE'RE GOING TO
GO 

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AHEAD AND GET STARTED HERE. 

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THANK YOU TO ALL OF YOU FOR 

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BEING HERE. I'M MICHAEL CHIANG 

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DIRECTOR OF THE NATIONAL EYE 

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INSTITUTE. I'M EXCITED ABOUT 

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WHAT THE NEXT FEW HOURS ARE 

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GOING TO BE FOR ALL OF US HERE 

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CH PLEASED TO WELCOME YOU TO THE

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JORAM PIATIGORSKY BASIC SCIENCE 

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LECTURE. WE HAVE AN INCREDIBLE 

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AWARDEE, COMING FROM THE OTHER 

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WASHINGTON, SEATTLE. DR. 

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PIATIGORSKY WILL INTRODUCE IN 

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MORE DETAIL. REALLY EXCITED, 

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RACHEL, TO HAVE YOU HERE. 

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WELCOME TO BETHESDA AND THE NIH.

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MY JOB IS TO TELL YOU ABOUT THIS

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DAY, HOW IT GOT TO BE. BASICALLY

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TELL YOU ABOUT DR. PIATIGORSKY 

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AND HIS LEGACY HERE. SO THIS IS 

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AN ENDOWMENT CREATED BASICALLY 

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TO HELP US RECOGNIZE WORK OF EYE

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AND VISION SCIENTISTS AT THE 

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FOREFRONT OF BASIC EYE SCIENCE 

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RESEARCH . I'M REALLY PROUD THIS

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AWARD IS NAMED FOR A SCIENTIST, 

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DR. PIATIGORSKY, WHO REALLY MADE

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CRUCIAL CONTRIBUTIONS TO OUR 

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SCIENTIFIC LEGACY HERE AT THE 

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NATIONAL EYE INSTITUTE. HE CAME 

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FROM NICHD, NATIONAL INSTITUTE 

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OF CHILD HEALTH AND DEVELOPMENT 

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IN 1981 TO SET UP BASICALLY ONE 

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OF THE FIRST LABS THAT STUDIED 

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THE MOLECULAR AND DEVELOPMENTAL 

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BIOLOGY OF VISION. HIS LAB 

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REALLY OPENED UP THE PRACTICE OF

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USING MOLECULAR BIOLOGY AND 

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GENETICS, LAB TECHNIQUES 

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INCLUDING GENE EXPRESSION AND 

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MECHANISMS OF THE EYE. JORAM'S 

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COLLEAGUES USED SQUID, SCALLOP, 

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OCTOPUS, JELLY FISH TO BASICALLY

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LEARN MUCH OF WHAT IS KNOWN 

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TODAY ABOUT CHRISTALINES IN 

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INVERTEBRATES. THIS HAS HELPED 

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DIVERSIFY THE CRISTALLINES AND 

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HELP IN THE CONVERGENCE IN 

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EVOLUTION. HIS LAB HAS 

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ESTABLISHED THE CORNEA TOGETHER 

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WITH LENS ACCUMULATE 

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MULTI FUNCTIONAL SPECIFIC 

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CRYSTALINES. THIS LED TO THE 

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FIRST CORNEAL PROMOTER FOR 

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ALDEHYDE 3A1 AND EXTENDED THE 

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NOTION OF THE CORNEAL 

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CRYSTALINES AS THE REFRACTON 

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HYPOTHESIS AND THAT THESE HAVE A

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LOT IN COMMON, THE USE OF CHRIS 

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THESE FOR OPTICAL PROPERTIES AND

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THE PROPOSAL WAS THEY SHOULD 

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CONSIDER USING THE LENS AND 

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CORNEA AS A SINGLE UNIT HE 

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CALLED THE REFRACTON. HE 

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SUPPORTED THIS BY DEMONSTRATING 

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CATARACT IN MICE WHO LACKED THE 

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GENE FOR THIS MAJOR CORNEAL 

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ALDEHYDE 3A1. WHEN JORAM WAS 

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CHIEF OF HIS LAB AT THE NEI THE 

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DEVELOPMENT LAB OF BIOLOGY HE 

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RECEIVED THE HELEN KELLER AWARD 

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IN 2008, PRESENTED BY THE HELEN 

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KELLER FOUNDATION FOR RESEARCH 

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AND EDUCATION FOR SIGNIFICANT 

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CONTRIBUTIONS DURING THE COURSE 

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OF A CAREER OR SINGLE 

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CONTRIBUTION FOR EXCEPTIONAL 

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IMPORTANCE TO VISION SCIENCE. SO

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THAT AWARD WON A NUMBER OF 

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AWARDS THAT REALLY MARKED THE 

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REMARKABLE CAREER THAT JORAM HAS

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HERE AT THE NATIONAL EYE 

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INSTITUTE. WHEN HE RETIRED HE 

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BECAME A WRITER AND WROTE ABOUT 

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THINGS LIKE FICTION, ESSAYS, A 

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MEMOIR. A COUPLE ARE ON MY 

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BOOKSHELF NOW. SO YOU'LL BE 

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HEARING ABOUT JORAM, YOU KNOW, 

90
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SHORTLY. BUT I JUST WANT TO 

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CLOSE MY REMARKS BY JUST 

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EXPRESSING MY EXPRESSION TO YOU,

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JORAM, TO YOUR WIFE LONA, WHO IS

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IN THE BACK HERE, AND TO THE 

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FNIH FOR MAKING THIS LECTURE 

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POSSIBLE AND BRINGING PEOPLE 

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LIKE DR. RACHEL WONG HERE. NOWLY

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TURN TO THE FNIH, THANK YOU. 

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   >> SURE, NO PROBLEM.
GOOD 

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AFTERNOON, EVERYONE. I'M SUSAN 

101
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CHILLINGLAW THE DIRECTOR OF GIFT

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PLANNING FOR FOUNDATION FOR 

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NATIONAL INSTITUTES OF HEALTH, 

104
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WITH MY COLLEAGUE REGINA MERIT, 

105
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IN THE BACK THERE. SHE IS OUR 

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DONOR RELATIONS AND FUND 

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OFFICER. LOVE COLLINS, OUR BOSS 

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AND VICE PRESIDENT OF 

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ADVANCEMENT COULDN'T BE WITH US 

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BUT SENDS HIS SALUTATIONS AND 

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CONGRATULATIONS TO DR. WONG. 

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WHAT WE TRY TO DO AT THE 

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FOUNDATION IS WORK WITH 

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BENEFACTORS TO CREATE 

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INITIATIVES THAT SUPPORT 

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RESEARCH, EDUCATION AND 

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ILLUMINATE RESEARCH THAT COMES 

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OUT OF THESE PARTNERSHIPS, SO WE

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ARE SO GRATEFUL TO LONNIE AND 

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JORAM PIATIGORSKY FOR THIS 

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INITIATIVE, WHICH WILL GO ON 

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WELL PAST YOUR LIFETIME. IT IS 

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QUITE A LEGACY, SO WE ARE SO 

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GRATEFUL TO YOU BOTH FOR THIS 

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INITIATIVE. NOW I'D LIKE TO TURN

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IT OVER TO JEREMY NATHANS, THE 

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CHAIR OF THE SELECTION COMMITTEE

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OF THE PIATIGORSKY AWARD. THANK 

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YOU SO MUCH. 

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[ APPLAUSE ]

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   >> I'M JEREMY NATHANS,
A 

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PROFESSOR AT JOHNS HOPKINS AND 

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INVESTIGATOR AT HOWARD HUGHES 

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MEDICAL INSTITUTE. IT IS A 

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REALLY GREAT HONOR TO BE HERE TO

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INTRODUCE JORAM, THEN 

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AFTER WARDS RACHEL WONG, OUR 

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HONOREE AND SPEAKER. WHAT 

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MICHAEL SAID IS THIS HONORS 

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CREATIVE SCIENCE AND CREATIVE 

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SCIENTIST JORAM PIATIGORSKY. 

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MIKE DESCRIBED JORAM WAS THE 

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FOUNDING DIRECTOR OF LABORATORY 

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OF MOLECULAR AND DEVELOPMENTAL 

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BIOLOGY AT THE NEI. STARTING 80s

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WHEN ALMOST NOTHING WAS KNOWN OF

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THIS JORAM EMBARK ON A QUEST TO 

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UNDERSTAND THE LEVEL OF THE 

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GENETIC BLUEPRINT. HE FOCUSED ON

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THE LENS, MIRACLE OF ENGINEERING

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AND EXPLORED THE STRUCTURE AND 

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DEVELOPMENT IN ORGANISMS, AS 

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MIKE SAID, IN ORGANISMS AS 

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DIVERSE AS JELLY FISH AND MICE. 

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LEADING TO INSIGHT THAT 

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ANATOMICALLY DIVERSE ORGANISMS 

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RETAIN REMARKABLE MOLECULAR 

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SIMILARITIES AND LED TO 

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DISCOVERY OF GENE-SHARING, A 

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MECHANISM IN WHICH A 

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SINGLE-PROTEIN PLAYS TWO ROLES 

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IN DIFFERENT CELL TYPES. I HAVE 

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KNOWN JORAM ABOUT 40 YEARS. I 

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ADMIRE MANY THINGS ABOUT HIM. I 

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ADMIRE HIS SCIENTIFIC 

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ORIGINALITY, HIS DETERMINATION 

167
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TO MARCH TO THE BEAT OF HIS OWN 

168
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DRUMMER. THE RESULT OF THAT 

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ORIGINALITY WAS THAT JORAM'S 

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COMBINATION OF INSIGHT HAS 

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YIELDED RICH REWARDS, MOST 

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DRAMATICALLY IN DISCOVERY OF 

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GENE SHARING BUT ALSO IN A WHOLE

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SERIES OF THOTHER INSIGHTS AND 

175
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DEVELOPMENT. I ADMIRE JORAM'S 

176
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DRIVE TO DEVELOP HIS 

177
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NON-SCIENTIFIC TALENTS. IN 

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PARTICULAR HIS TALENT AS A 

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WRITER, WHICH HE HAS DONE WITH 

180
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EXTRAORDINARY SUCCESS. THE 

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GENRES OF JORAM'S PUBLISHED 

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BOOKS ENCOMPASS SCIENTIFIC 

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TREATISE, FICTION, AUTOBIOGRAPHY

184
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AND ESSAYS. I JUST COMPLETED HIS

185
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ESSAY COLLECTION A FEW MONTHS 

186
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AGO, IT IS FANTASTIC. I ADMIRE 

187
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JORAM'S KINDNESS AND WISDOM. SO 

188
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WITH THIS LECTURE AND AWARD 

189
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JORAM AND LONA HAVE MADE AN 

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ENDURING GIFT THAT WILL BRING 

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CREATIVE SCIENTISTS TO THIS 

192
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CAMPUS AND INSPIRE THE NEXT 

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GENERATION OF RESEARCHERS, THANK

194
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YOU. 

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[ APPLAUSE ]

196
00:09:04,694 --> 00:09:06,930
   >> I DIDN'T REALIZE I
WAS 

197
00:09:06,930 --> 00:09:09,733
SUPPOSED TO SPEAK. I WON'T SPEAK

198
00:09:09,733 --> 00:09:12,102
LONGER THAN AN HOUR. 

199
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[ LAUGHTER ]

200
00:09:12,669 --> 00:09:15,839
   >> I'M REALLY HAPPY TO
SEE 

201
00:09:15,839 --> 00:09:19,743
THIS LECTURE AWARD NOW GOING 

202
00:09:19,743 --> 00:09:21,211
INTO ITS SECOND YEAR. IT WILL BE

203
00:09:21,211 --> 00:09:23,113
GOING ON FAR BEYOND THAT. TO 

204
00:09:23,113 --> 00:09:27,584
HAVE CONTINUED EXCELLENCE WITH 

205
00:09:27,584 --> 00:09:32,188
RACHEL WONG TO GIVE OUR SECOND 

206
00:09:32,188 --> 00:09:38,528
AWARDEE, THE TALK FOR TODAY. I 

207
00:09:38,528 --> 00:09:40,997
STARTED THIS AWARD FOR SEVERAL 

208
00:09:40,997 --> 00:09:44,768
DIFFERENT REASONS. ONE IS THAT 

209
00:09:44,768 --> 00:09:47,270
NIH AND NEI HAS BEEN SO 

210
00:09:47,270 --> 00:09:51,408
EXTRAORDINARY FAINEAR GOOD TO M 

211
00:09:51,408 --> 00:09:53,710
WANTED TO GIVE BACK. THEY HAVE 

212
00:09:53,710 --> 00:09:56,046
FUNDED MY WORK, MY LABORATORY, I

213
00:09:56,046 --> 00:10:02,786
DON'T KNOW HOW MANY YEARS I WAS 

214
00:10:02,786 --> 00:10:04,688
AT NIEHS, 45 YEARS, AND NEVER AT

215
00:10:04,688 --> 00:10:07,424
ANY POINT DID ANYONE COME TO ME 

216
00:10:07,424 --> 00:10:09,392
AND SAY WHAT I SHOULD BE WORKING

217
00:10:09,392 --> 00:10:12,095
ON. I WAS GIVEN ACADEMIC 

218
00:10:12,095 --> 00:10:14,497
FREEDOM. THAT IS SO INVALUABLE 

219
00:10:14,497 --> 00:10:17,467
TO DO BASIC RESEARCH. I AM SO 

220
00:10:17,467 --> 00:10:19,035
GRATEFUL FOR THAT. WHICH BRINGS 

221
00:10:19,035 --> 00:10:21,905
ME TO THE SECOND REASON FOR 

222
00:10:21,905 --> 00:10:23,373
GIVING THE AWARD, IS THAT I 

223
00:10:23,373 --> 00:10:28,345
WANTED TO HELP IN SOME SMALL WAY

224
00:10:28,345 --> 00:10:32,515
TO PERPETUATE THE IMPORTANCE OF 

225
00:10:32,515 --> 00:10:33,883
BASIC RESEARCH. WE STRESS THE 

226
00:10:33,883 --> 00:10:35,885
IMPORTANCE OF CLINICAL WORK. I 

227
00:10:35,885 --> 00:10:38,421
IN NO WAY MEAN TO DEROGATORY 

228
00:10:38,421 --> 00:10:39,889
STATEMENTS ABOUT THAT OR TO SAY 

229
00:10:39,889 --> 00:10:42,559
IT SHOULDN'T BE SUPPORTED EVEN 

230
00:10:42,559 --> 00:10:47,364
MORE. IT IS CRUCIAL. BUT IT ALSO

231
00:10:47,364 --> 00:10:50,400
FOLLOWS ON THE FOOTSTEPS OF THE 

232
00:10:50,400 --> 00:10:53,603
BASIC RESEARCHER. PEOPLE OFTEN 

233
00:10:53,603 --> 00:10:55,705
SAY BASIC RESEARCH WHERE YOU ARE

234
00:10:55,705 --> 00:11:00,176
STUDYING FUNDAMENTAL PROCESSES 

235
00:11:00,176 --> 00:11:02,712
IS CURIOSITY-DRIVEN. AND I 

236
00:11:02,712 --> 00:11:04,581
REALLY HAVE -- I DON'T AGREE 

237
00:11:04,581 --> 00:11:05,982
WITH THAT IN THE SENSE THAT I'M 

238
00:11:05,982 --> 00:11:08,818
NOT AWARE OF ANY KIND OF 

239
00:11:08,818 --> 00:11:10,854
RESEARCH IN ANY AREA THAT 

240
00:11:10,854 --> 00:11:12,856
DOESN'T INVOLVE CURIOSITY. WHAT 

241
00:11:12,856 --> 00:11:15,692
I THINK IS CRITICAL ABOUT BASIC 

242
00:11:15,692 --> 00:11:18,561
RESEARCH IS THAT IT IS 

243
00:11:18,561 --> 00:11:20,497
DESTINATION-FREE. THAT SEEMS TO 

244
00:11:20,497 --> 00:11:22,265
BE THE IMPORTANT POINT. THAT 

245
00:11:22,265 --> 00:11:27,771
EACH FINDING IS GOING TO 

246
00:11:27,771 --> 00:11:28,304
PROBA

247
00:11:28,304 --> 00:11:32,175
PROBABLY GOING TO UPSET YOUR 

248
00:11:32,175 --> 00:11:33,910
PREVIOUS IDEAS AND EACH PAPER 

249
00:11:33,910 --> 00:11:36,579
WILL HAVE YOU CONSIDER THINGS 

250
00:11:36,579 --> 00:11:38,081
DIFFERENTLY AND THE OPEN MIND IS

251
00:11:38,081 --> 00:11:39,983
THAT NOT " I WANT TO CURE THIS 

252
00:11:39,983 --> 00:11:42,352
DISEASE " BUT THE IDEA IS TO 

253
00:11:42,352 --> 00:11:43,720
REALLY UNDERSTAND, TO MY LAST 

254
00:11:43,720 --> 00:11:46,689
POINT BEFORE I GO, IS THAT I WAS

255
00:11:46,689 --> 00:11:50,827
ON A PANEL MANY YEARS AGO ABOUT 

256
00:11:50,827 --> 00:11:54,898
PRIORITIES FOR FUNDING GRANTS. 

257
00:11:54,898 --> 00:11:58,568
IN THAT DISCUSSION AMONG THE 

258
00:11:58,568 --> 00:12:01,671
PANELISTS UP THERE WAS THE IDEA 

259
00:12:01,671 --> 00:12:04,340
THAT THE HUMAN CATARACT SHOULD 

260
00:12:04,340 --> 00:12:06,443
BE THE HIGHEST PRIORITY. ONE OF 

261
00:12:06,443 --> 00:12:09,279
THE THINGS THAT I THINK I HELPED

262
00:12:09,279 --> 00:12:12,082
INFLUENCE, WHICH WAS REALLY 

263
00:12:12,082 --> 00:12:14,451
IMPORTANT TO ME, IS THAT 

264
00:12:14,451 --> 00:12:15,452
ULTIMATELY WHAT WAS NOW 

265
00:12:15,452 --> 00:12:18,521
CONSIDERED THE HIGHEST PRIORITY 

266
00:12:18,521 --> 00:12:21,391
FOR RESEARCHING THE LENS WAS THE

267
00:12:21,391 --> 00:12:23,460
NORMAL LENS. NOT EVEN THE HUMAN 

268
00:12:23,460 --> 00:12:27,697
NORMAL LENS BUT THE NORMAL LENS 

269
00:12:27,697 --> 00:12:28,298
BECAUSE IN FACT, WHETHER YOU 

270
00:12:28,298 --> 00:12:31,801
LOOK AT A JELLY FISH, A SCALLOP 

271
00:12:31,801 --> 00:12:37,340
OR A COW OR YOUR ROOMMATE, THEY 

272
00:12:37,340 --> 00:12:37,907
ALL HAVE , IN FACT, 

273
00:12:37,907 --> 00:12:42,745
 SIMILARITIES AND FANTASTICALLY 

274
00:12:42,745 --> 00:12:45,281
INTERESTING DIFFERENCES THAT ARE

275
00:12:45,281 --> 00:12:51,221
RELEVANT TO THE ENVIRONMENT, 

276
00:12:51,221 --> 00:12:54,390
EVEN ANIMALS THAT ARE CALLED 

277
00:12:54,390 --> 00:12:55,959
PRIMITIVE ARE NOT PRIMITIVE BY 

278
00:12:55,959 --> 00:13:00,230
ANY MEANS AT ALL; WHAT THEY ARE 

279
00:13:00,230 --> 00:13:06,569
IS EXTREMELY WELL -- THAT IS THE

280
00:13:06,569 --> 00:13:15,378
CRITICAL THING, HOW DID THEY DO 

281
00:13:15,378 --> 00:13:17,447
THAT, UNDERSTANDING NORMAL 

282
00:13:17,447 --> 00:13:19,382
TISSUES. I'M SURE DR. WONG WILL 

283
00:13:19,382 --> 00:13:20,617
HELP ME UNDERSTAND THAT QUEST 

284
00:13:20,617 --> 00:13:22,585
AND FEEL THIS AWARD WILL HELP IN

285
00:13:22,585 --> 00:13:24,387
TERMS OF GIVING FROM INSTEAD OF 

286
00:13:24,387 --> 00:13:27,524
THE OUTSIDE WORLD TO HOW THE EYE

287
00:13:27,524 --> 00:13:29,425
WORKS BUT HOW THE EYE WORKS. IT 

288
00:13:29,425 --> 00:13:30,693
IS FROM THE EYE TO THE WORLD, 

289
00:13:30,693 --> 00:13:34,764
NOT FROM THE WORLD TO THE EYE. 

290
00:13:34,764 --> 00:13:37,800
SO THANK YOU VERY MUCH. 

291
00:13:37,800 --> 00:13:46,209
[ APPLAUSE ]

292
00:13:46,209 --> 00:13:49,913
   >> OKAY. I'M GOING TO 

293
00:13:49,913 --> 00:13:51,481
INTRODUCE OUR SPEAKER TODAY, 

294
00:13:51,481 --> 00:13:53,950
RACHEL WONG. IT IS A PLEASURE, 

295
00:13:53,950 --> 00:13:58,555
RACHEL, TO INTRODUCE YOU AS THE 

296
00:13:58,555 --> 00:13:59,956
2024 PIATIGORSKY LECTURE AND 

297
00:13:59,956 --> 00:14:03,560
AWARD RECIPIENT. RACHEL IS A 

298
00:14:03,560 --> 00:14:05,328
NEUROBIOLOGIST WIDELY RECOGNIZED

299
00:14:05,328 --> 00:14:06,996
FOR HER WORK ON DEVELOPMENTAL 

300
00:14:06,996 --> 00:14:11,334
MAKE NFLS OF THE ASSEMBLY OF 

301
00:14:11,334 --> 00:14:16,873
NEURONAL CIRCUITS, EXPLORING 

302
00:14:16,873 --> 00:14:19,842
ACTIVITY-DEPENDENT AND 

303
00:14:19,842 --> 00:14:21,611
INDEPENDENT CUES IN THE RETINAL 

304
00:14:21,611 --> 00:14:26,749
SYSTEM, PARTICULARLY IN 

305
00:14:26,749 --> 00:14:30,320
VERTEBRA. IN RACHEL'S PAPERS 

306
00:14:30,320 --> 00:14:33,323
IMAGES OF CELLS AND ISSUES AND 

307
00:14:33,323 --> 00:14:34,958
RETINA ARE BEAUTIFUL AND IS 

308
00:14:34,958 --> 00:14:37,527
READER IS AWARDED WITH A 

309
00:14:37,527 --> 00:14:38,828
SCIENTIFIC AND AESTHETIC TREAT. 

310
00:14:38,828 --> 00:14:41,564
SHE GREW UP IN MALAYSIA AND 

311
00:14:41,564 --> 00:14:43,666
RECEIVED A BACHELORS IN PHYSICS 

312
00:14:43,666 --> 00:14:48,638
AND OBTAINED A PHD IN VISUAL 

313
00:14:48,638 --> 00:14:50,106
NEUROSCIENCE FROM AUSTRALIA 

314
00:14:50,106 --> 00:14:53,109
NATIONAL UNIVERSITY. DID 

315
00:14:53,109 --> 00:14:54,143
POST-GRADUATE RESEARCH AT THE 

316
00:14:54,143 --> 00:14:56,346
VISION RESEARCH INSTITUTE IN 

317
00:14:56,346 --> 00:14:58,081
AUSTRALIA, STANFORD AND VISION, 

318
00:14:58,081 --> 00:14:59,048
TOUCH AND HEARING RESEARCH 

319
00:14:59,048 --> 00:15:02,852
CENTER IN AUSTRALIA. IN 1994 SHE

320
00:15:02,852 --> 00:15:04,687
JOINED THE FACULTY AT WASHINGTON

321
00:15:04,687 --> 00:15:07,590
SCHOOL OF MEDICINE IN ST. LOUIS 

322
00:15:07,590 --> 00:15:12,962
AND 2006 MOVED TO SEATTLE, 

323
00:15:12,962 --> 00:15:13,529
PROFESSOR AND CHAIR OF 

324
00:15:13,529 --> 00:15:15,031
DEPARTMENT OF BIOLOGICAL 

325
00:15:15,031 --> 00:15:16,599
STRUCTURE. HAS RECEIVED MANY 

326
00:15:16,599 --> 00:15:20,069
AWARDS INCLUDING THE FREEDOM 

327
00:15:20,069 --> 00:15:21,604
AWARD FOR RESEARCH IN VISION AND

328
00:15:21,604 --> 00:15:24,941
OPT MOLL GI AND BRIAN BOYCOTT 

329
00:15:24,941 --> 00:15:26,342
PRIZE AND ELECTION TO THE 

330
00:15:26,342 --> 00:15:27,977
NATIONAL ACADEMY OF SCIENCES. 

331
00:15:27,977 --> 00:15:29,212
CONGRATULATIONS, RACHEL. WE LOOK

332
00:15:29,212 --> 00:15:38,688
FORWARD TO YOUR LO LECTURE. 

333
00:15:38,688 --> 00:15:38,988
[ APPLAUSE ]

334
00:15:38,988 --> 00:15:41,090
   >> SO I'M ALMOST SPEECH
LESS,

335
00:15:41,090 --> 00:15:42,659
WHICH MEANS THAT WILL BE VERY 

336
00:15:42,659 --> 00:15:44,761
SHORT. THANK YOU SO MUCH FOR 

337
00:15:44,761 --> 00:15:47,263
THAT VERY KIND INTRODUCTION, 

338
00:15:47,263 --> 00:15:48,064
JEREMY. I HAVE KNOWN JEREMY FOR 

339
00:15:48,064 --> 00:15:53,636
A LONG TIME. I JUST MET JORAM 

340
00:15:53,636 --> 00:16:00,710
PIATIGORSKY. I'M EXTREMELY HO

341
00:16:00,710 --> 00:16:02,412
HONORED. THIS REALLY JIVES WITH 

342
00:16:02,412 --> 00:16:05,148
ME. YOU WILL SEE THE NUMBER OF 

343
00:16:05,148 --> 00:16:06,482
SPECIES WE HAVE GONE THROUGH 

344
00:16:06,482 --> 00:16:08,785
THROUGH MY TIME AS AN 

345
00:16:08,785 --> 00:16:11,020
INVESTIGATOR IS QUITE EXTENSIVE.

346
00:16:11,020 --> 00:16:13,256
MY FATHER USED TO ASK ME, 

347
00:16:13,256 --> 00:16:14,724
HAVEN'T YOU JUST FOUND ONE MODEL

348
00:16:14,724 --> 00:16:17,827
YOU CAN USE. I WAS LIKE, NO. 

349
00:16:17,827 --> 00:16:21,164
EVERY EYE IN A DIFFERENT ANIMAL 

350
00:16:21,164 --> 00:16:23,132
OR EYE IN DIFFERENT ANIMAL USES 

351
00:16:23,132 --> 00:16:25,601
A DIFFERENT STRATEGY TO MAKE ITS

352
00:16:25,601 --> 00:16:28,004
OWN RETINA SO IT CAN BASICALLY 

353
00:16:28,004 --> 00:16:29,238
PROCESS THE VISUAL WORLD FOR THE

354
00:16:29,238 --> 00:16:31,040
IMPORTANT THINGS FOR THAT 

355
00:16:31,040 --> 00:16:33,843
ANIMAL. SO I THINK COMPARATIVE 

356
00:16:33,843 --> 00:16:34,811
NEUROBIOLOGY IS EXTREMELY 

357
00:16:34,811 --> 00:16:36,012
IMPORTANT BUT JUST WANTING TO 

358
00:16:36,012 --> 00:16:37,113
UNDERSTAND HOW THINGS WORK AND 

359
00:16:37,113 --> 00:16:39,882
HOW THE RETINA WORKS TO INFORM 

360
00:16:39,882 --> 00:16:42,985
US OF WHAT -- WHEN THINGS GO 

361
00:16:42,985 --> 00:16:45,955
WRONG, WHY DOES IT WORK AND HOW 

362
00:16:45,955 --> 00:16:47,390
YOU MIGHT PUT IT BACK TOGETHER. 

363
00:16:47,390 --> 00:16:51,394
THIS ISN'T MY TALK. I WILL TRY 

364
00:16:51,394 --> 00:17:01,738
TO GET TO MY TALK. 

365
00:17:02,572 --> 00:17:06,042
    ALL RIGHT. BECAUSE WE HAVE 

366
00:17:06,042 --> 00:17:08,711
TWO SCREENS I HAVE DECIDED NOT 

367
00:17:08,711 --> 00:17:11,080
TO USE THE LASER POINTER SO I 

368
00:17:11,080 --> 00:17:13,883
HAVE A MOUSE THING MOVING 

369
00:17:13,883 --> 00:17:15,585
AROUND. IF YOU DON'T SEE IT THIS

370
00:17:15,585 --> 00:17:17,820
WAY, THIS IS THE LOW CONTRAST 

371
00:17:17,820 --> 00:17:19,322
SCREEN, THAT IS THE HIGH 

372
00:17:19,322 --> 00:17:20,790
CONTRAST SCREEN. WHICHEVER WORKS

373
00:17:20,790 --> 00:17:23,426
FOR YOU I THINK IS FINE WITH ME.

374
00:17:23,426 --> 00:17:25,428
SO I THINK I HAVE LESS THAN AN 

375
00:17:25,428 --> 00:17:27,330
HOUR. I'M GOING TO GET GOING SO 

376
00:17:27,330 --> 00:17:29,699
YOU CAN ACTUALLY END UP WITH 

377
00:17:29,699 --> 00:17:31,334
RECEPTION. HOPE YOU HAD LUNCH 

378
00:17:31,334 --> 00:17:33,936
ALREADY SO CAN KIND OF PAY 

379
00:17:33,936 --> 00:17:35,338
ATTENTION. NOW AS JERRY 

380
00:17:35,338 --> 00:17:36,739
MENTIONED FOR MANY YEARS MY 

381
00:17:36,739 --> 00:17:38,408
LAB'S BEEN INTERESTED IN 

382
00:17:38,408 --> 00:17:40,376
DEVELOPMENT OF RETINA, 

383
00:17:40,376 --> 00:17:42,178
PARTICULARLY THE VERTEBRATE 

384
00:17:42,178 --> 00:17:43,913
RETINA. WE HAVE ALSO IN RECENT 

385
00:17:43,913 --> 00:17:45,581
YEARS BEEN INTERESTED IN REPAIR.

386
00:17:45,581 --> 00:17:47,717
WE FIGURED WE COULD USE SOME OF 

387
00:17:47,717 --> 00:17:49,352
TECHNIQUES WE HAVE MUSTERED 

388
00:17:49,352 --> 00:17:50,720
TOGETHER TO STUDY THE 

389
00:17:50,720 --> 00:17:52,021
DEVELOPMENT OF THE RETINA 

390
00:17:52,021 --> 00:17:53,523
TOWARDS A BETTER UNDERSTANDING 

391
00:17:53,523 --> 00:17:55,925
NOT SO MUCH OF HOW TO REPAIR THE

392
00:17:55,925 --> 00:17:58,561
RETINA, IN MY CASE, BUT REALLY 

393
00:17:58,561 --> 00:18:02,031
TO UNDERSTAND THE HURDLES THAT 

394
00:18:02,031 --> 00:18:04,200
THE ADULT RETINA MIGHT FACE IN 

395
00:18:04,200 --> 00:18:06,702
ORDER TO REPAIR ITS CIRCUITRY 

396
00:18:06,702 --> 00:18:09,205
EITHER IN DISEASE OR IN INJURY. 

397
00:18:09,205 --> 00:18:10,573
SO MOST OF THE TALK I WILL TELL 

398
00:18:10,573 --> 00:18:12,341
YOU ABOUT -- I WILL WALK YOU 

399
00:18:12,341 --> 00:18:14,677
THROUGH A JOURNEY OF OURS WHERE 

400
00:18:14,677 --> 00:18:16,813
WE HAVE TRIED TO UNDERSTAND 

401
00:18:16,813 --> 00:18:18,614
BASICALLY WHAT THE MECHANISMS 

402
00:18:18,614 --> 00:18:19,515
ARE, ESPECIALLY CELL 

403
00:18:19,515 --> 00:18:20,550
INTERACTIONS THAT ARE IMPORTANT 

404
00:18:20,550 --> 00:18:23,286
FOR SETTING UP PARTICULARLY THE 

405
00:18:23,286 --> 00:18:24,921
CIRCUITRY OF THE RETINA, SO THIS

406
00:18:24,921 --> 00:18:26,322
WILL BE DEVELOPMENT. TOWARDS THE

407
00:18:26,322 --> 00:18:28,724
END I WANT TO SHARE SOME OF OUR 

408
00:18:28,724 --> 00:18:30,493
REASON TO WORK AND TRYING TO 

409
00:18:30,493 --> 00:18:32,094
UNDERSTAND HOW CIRCUITS FALL 

410
00:18:32,094 --> 00:18:33,129
APART. MAYBE WHAT WE MIGHT NEED 

411
00:18:33,129 --> 00:18:34,964
TO THINK ABOUT IN TERMS OF HOW 

412
00:18:34,964 --> 00:18:37,233
WE MIGHT NEED TO PUT IT BACK 

413
00:18:37,233 --> 00:18:39,635
TOGETHER. SO THIS IS ALSO 

414
00:18:39,635 --> 00:18:42,672
ESPECIALLY FOR ANAN, WHO BROUGHT

415
00:18:42,672 --> 00:18:45,441
ME HERE MANY YEARS AGO TO GIVE 

416
00:18:45,441 --> 00:18:47,376
THE WALLS LECTURE. ONE OF THE 

417
00:18:47,376 --> 00:18:49,111
PROGRAM OFFICERS ASKED ME, ARE 

418
00:18:49,111 --> 00:18:51,214
YOU GOING TO WORK ON DISEASE? I 

419
00:18:51,214 --> 00:18:54,784
SAID I GUESS I'M AT THE NIEHS SO

420
00:18:54,784 --> 00:18:58,521
THE ANSWER WOULD BE YES. WE DID 

421
00:18:58,521 --> 00:19:04,026
GO BACK AND WE DID START 

422
00:19:04,026 --> 00:19:05,528
SOMETHING USING SOME OF THE 

423
00:19:05,528 --> 00:19:07,063
TECHNIQUES. THAT WAS VERY 

424
00:19:07,063 --> 00:19:08,831
INSTRUCTIVE. BUT TODAY LET ME 

425
00:19:08,831 --> 00:19:10,066
REMIND YOU -- AND I DON'T THINK 

426
00:19:10,066 --> 00:19:11,801
I NEED TO DO MUCH IN TERMS OF 

427
00:19:11,801 --> 00:19:14,136
GOING THROUGH THIS. WE ALL 

428
00:19:14,136 --> 00:19:15,338
APPRECIATE THE WONDERFUL AND 

429
00:19:15,338 --> 00:19:16,372
BEAUTIFUL STRUCTURE OF THE 

430
00:19:16,372 --> 00:19:17,940
VERTEBRATE RETINA. WE KNOW HOW 

431
00:19:17,940 --> 00:19:21,244
THE CELLS ARE LAYERED. WE KNOW 

432
00:19:21,244 --> 00:19:23,980
ITS CONNECTIVITY IS NOT HAPPEN 

433
00:19:23,980 --> 00:19:25,114
HAZARD. THAT IN FACT, THERE ARE 

434
00:19:25,114 --> 00:19:28,818
LOTS OF PATHWAYS THAT CHANNEL 

435
00:19:28,818 --> 00:19:30,686
VISUAL INFORMATION FROM 

436
00:19:30,686 --> 00:19:33,189
RECEPTORS TO RETINAL GANGLION 

437
00:19:33,189 --> 00:19:35,191
CELLS. WE KNOW ABOUT THE ROCK 

438
00:19:35,191 --> 00:19:37,026
PATHWAY, WHICH DEALS WITH DIM 

439
00:19:37,026 --> 00:19:39,262
LIGHT LEVELS AND KNOW ABOUT THE 

440
00:19:39,262 --> 00:19:40,930
CONE PATHWAY, IMPORTANT FOR 

441
00:19:40,930 --> 00:19:42,265
THINGS LIKE COLOR, WHERE YOU 

442
00:19:42,265 --> 00:19:44,267
WILL SEE MY SLIDES AND MAYBE 

443
00:19:44,267 --> 00:19:46,402
EVEN READ SOME OF THE LETTERS ON

444
00:19:46,402 --> 00:19:48,070
THOSE SLIDES. PHOTO RECEPTORS, 

445
00:19:48,070 --> 00:19:54,610
THE RODS AND CONES HAVE CAUSED 

446
00:19:54,610 --> 00:19:57,113
CYNOTIC INFORMATION THROUGH 

447
00:19:57,113 --> 00:19:59,949
BIPOLAR CELLS, ROD AND COMBINE 

448
00:19:59,949 --> 00:20:03,185
CELLS CONNECT TO GANGION THAT 

449
00:20:03,185 --> 00:20:07,089
SEND THAT TO BRAIN. WITH E KNOW 

450
00:20:07,089 --> 00:20:09,926
ABOUT MODULAR CONNECTIONS 

451
00:20:09,926 --> 00:20:11,861
VERTICAL PATHWAY BY HORIZON 

452
00:20:11,861 --> 00:20:13,963
CELLS IN RETINA AND 

453
00:20:13,963 --> 00:20:18,334
NEUROSURGEONS WHICH ARE 

454
00:20:18,334 --> 00:20:19,869
INHIBITORY THAT SHAPE 

455
00:20:19,869 --> 00:20:21,103
CONNECTIONS THAT ARE CROSS 

456
00:20:21,103 --> 00:20:23,806
BETWEEN BI AND GANGLION CELLS. 

457
00:20:23,806 --> 00:20:25,541
FOR THOSE THAT STUDY CELLS IN 

458
00:20:25,541 --> 00:20:26,943
THE RETINA YOU WILL APPRECIATE 

459
00:20:26,943 --> 00:20:28,744
THEY ARE NOT ONLY ROD AND CONE 

460
00:20:28,744 --> 00:20:30,713
PATHWAYS BUT MANY YEARS AGO, I 

461
00:20:30,713 --> 00:20:32,582
WON'T SAY HOW MANY BECAUSE RALPH

462
00:20:32,582 --> 00:20:37,920
IS HERE, WE KNOW THERE ARE 

463
00:20:37,920 --> 00:20:38,955
ON-AND-OFF PATHWAYS THAT CHANNEL

464
00:20:38,955 --> 00:20:40,923
INFORMATION RESPONSES IN TWO 

465
00:20:40,923 --> 00:20:43,826
WAYS. SO WHEN YOU TURN ON THE 

466
00:20:43,826 --> 00:20:46,362
ROOM LIGHT THE ON WOULD BE 

467
00:20:46,362 --> 00:20:48,864
POLARIZED AND LIGHT UP. AT THE 

468
00:20:48,864 --> 00:20:51,667
SAME TIME THE OFF PATHWAY WILL 

469
00:20:51,667 --> 00:20:58,541
BE SUPPRESSED, POLARIZED, A 

470
00:20:58,541 --> 00:20:59,609
YINYANG INFORMATION HOW YOU 

471
00:20:59,609 --> 00:21:01,711
CONVEY PATHWAYS ACROSS THE 

472
00:21:01,711 --> 00:21:02,712
RETINA. THE WONDERFUL THING 

473
00:21:02,712 --> 00:21:04,313
ABOUT THE RETINA TOO IS YOU CAN 

474
00:21:04,313 --> 00:21:05,748
IMMEDIATELY GUESS WHAT SOME OF 

475
00:21:05,748 --> 00:21:07,149
THE FUNCTION MIGHT BE SIMPLY BY 

476
00:21:07,149 --> 00:21:08,651
LOOKING AT THE STRUCTURE 

477
00:21:08,651 --> 00:21:10,953
ORGANIZATION. WE KNOW, FOR 

478
00:21:10,953 --> 00:21:15,057
EXAMPLE, ON-AND-OFF CIRCUITS ARE

479
00:21:15,057 --> 00:21:19,595
REALLY SEPARATED MOSTLY 

480
00:21:19,595 --> 00:21:22,198
INTERDISTINCTLY IN THE RETINA. 

481
00:21:22,198 --> 00:21:24,333
FOR A NEUROBIOLOGIST, INTERESTED

482
00:21:24,333 --> 00:21:26,469
IN VISION, IF YOU WANT TO LOOK 

483
00:21:26,469 --> 00:21:29,238
WHERE ALL THE CIRCUITRY IN EYES 

484
00:21:29,238 --> 00:21:30,906
AND GUESS WHAT FUNCTION MIGHT BE

485
00:21:30,906 --> 00:21:33,175
YOU CAN DO A LOT BASED ON THE 

486
00:21:33,175 --> 00:21:35,044
STRUCTURE OF ORGANIZATION. NOW 

487
00:21:35,044 --> 00:21:36,679
TO START AT THE -- JUST TO 

488
00:21:36,679 --> 00:21:38,481
FINISH OFF THIS PART, I SHOULD 

489
00:21:38,481 --> 00:21:39,515
REMIND YOU OF COURSE WITHIN EACH

490
00:21:39,515 --> 00:21:43,085
OF THE MAJOR CLASSES OF NEURONS 

491
00:21:43,085 --> 00:21:45,021
IN THE RETINA, MANY TYPES -- AND

492
00:21:45,021 --> 00:21:48,090
THAT IS TO REMIND YOU OF ITS 

493
00:21:48,090 --> 00:21:50,226
COMPLEXITY. EVEN OF GANGLION 

494
00:21:50,226 --> 00:21:52,495
CELLS, THE ON-AND-OFF, THERE ARE

495
00:21:52,495 --> 00:21:57,066
NOT ONLY TWO TYPES BUT MANY 

496
00:21:57,066 --> 00:22:00,236
DISTINGUISHED BY THEIR 

497
00:22:00,236 --> 00:22:01,303
MORPHOLOGY AND DISTINCTION. THIS

498
00:22:01,303 --> 00:22:04,440
IS ONLY TWO. WHAT ARE YOU DOING 

499
00:22:04,440 --> 00:22:07,043
HERE? MOST DEVELOPMENTAL 

500
00:22:07,043 --> 00:22:07,677
NEUROBIOLOGISTS, YOU NEED TO 

501
00:22:07,677 --> 00:22:09,512
UNDERSTAND HOW CELLS ARE MADE 

502
00:22:09,512 --> 00:22:12,415
AND THE RIGHT TYPES AND THE 

503
00:22:12,415 --> 00:22:14,984
RIGHT TIME. CAN Y'ALL SEE THIS 

504
00:22:14,984 --> 00:22:16,519
OKAY, THE LOW-CONTRAST SCREEN? 

505
00:22:16,519 --> 00:22:20,089
THEN YOU HAVE TO HAVE FACTORS 

506
00:22:20,089 --> 00:22:22,992
THAT CAUSE THESE CELL, THESE 

507
00:22:22,992 --> 00:22:27,930
NEURONS TO GROW IN DIFFERENT 

508
00:22:27,930 --> 00:22:38,674
COMPARTMENTS LIKE A A /* AXONS 

509
00:22:40,076 --> 00:22:42,344
AND DENDRITES. SO THINGS TAKE 

510
00:22:42,344 --> 00:22:44,680
PLACE DURING DEVELOPMENT. IT IS 

511
00:22:44,680 --> 00:22:48,184
NOT JUST STRUCTURALLY DIFFERENT 

512
00:22:48,184 --> 00:22:49,552
BUT FUNCTIONS WITH THESE 

513
00:22:49,552 --> 00:22:53,556
NEURONS. THEN THE NEXT STEP, 

514
00:22:53,556 --> 00:22:56,859
WHICH IS REALLY IMPORTANT, IT 

515
00:22:56,859 --> 00:22:58,694
MAKES THE RIGHT PARTNERS AND 

516
00:22:58,694 --> 00:23:01,564
RIGHT SYNAPSES. NOT JUST THE 

517
00:23:01,564 --> 00:23:03,299
RIGHT TYPE BUT THE RIGHT NUMBER 

518
00:23:03,299 --> 00:23:05,534
OF SYNAPSES AND THIS INFLUENCES 

519
00:23:05,534 --> 00:23:07,503
PROPERLY WITHIN THE CIRCUITRY SO

520
00:23:07,503 --> 00:23:09,171
EVENTUALLY YOU END UP WITH 

521
00:23:09,171 --> 00:23:10,406
NEURONS THAT PAIR UP AND MAKE 

522
00:23:10,406 --> 00:23:12,108
CONNECTIONS WITH EACH OTHER. 

523
00:23:12,108 --> 00:23:16,312
IMAGINE FOR THE VERTEBRATE 

524
00:23:16,312 --> 00:23:18,013
RETINA YOU HAVE TO MAKE THESE 

525
00:23:18,013 --> 00:23:19,982
ALMOST THE SAME TIME SO THE 

526
00:23:19,982 --> 00:23:21,016
SEQUENCE IS MOSTLY IN PARALLEL 

527
00:23:21,016 --> 00:23:23,886
SO MANY PROCESSES HAVE TO TAKE 

528
00:23:23,886 --> 00:23:25,554
PLACE FOR CO -GENERATION OF 

529
00:23:25,554 --> 00:23:27,256
CIRCUITS TO MAKE SURE THEY ALL 

530
00:23:27,256 --> 00:23:29,325
WIRE PROPERLY. WE HAVE MOSTLY IN

531
00:23:29,325 --> 00:23:30,659
THE LAST YEARS I THINK FOCUSED 

532
00:23:30,659 --> 00:23:33,896
ON THIS PART OF DEVELOPMENT, 

533
00:23:33,896 --> 00:23:35,898
WHICH IS TRY TO UNDERSTAND THE 

534
00:23:35,898 --> 00:23:37,767
MECHANISMS THAT SHAPE THE 

535
00:23:37,767 --> 00:23:39,835
CIRCUITRY BETWEEN CELLS IN THE 

536
00:23:39,835 --> 00:23:41,504
RETINA. TO DO SO WE HAVE USED A 

537
00:23:41,504 --> 00:23:44,807
VARIETY OF TECHNIQUES, WHICH 

538
00:23:44,807 --> 00:23:46,175
WILL BECOME OBVIOUS SOON. 

539
00:23:46,175 --> 00:23:48,444
IMPORTANTLY WE HAVE DONE THIS IN

540
00:23:48,444 --> 00:23:50,513
A VARIETY OF SPECIES. THIS IS 

541
00:23:50,513 --> 00:23:53,215
ONLY A SMALL HANDFUL RELATED TO 

542
00:23:53,215 --> 00:23:56,185
THE SLIDES FOR TODAY. FROM CHICK

543
00:23:56,185 --> 00:23:58,554
ALL THE WAY TO HUMAN SO WE CAN 

544
00:23:58,554 --> 00:24:00,990
THINK ABOUT HOW THE VERTEBRATE 

545
00:24:00,990 --> 00:24:03,959
RETINA, WHAT MECHANISMS ARE USED

546
00:24:03,959 --> 00:24:05,628
AND ARE COMMON BUT ALSO 

547
00:24:05,628 --> 00:24:07,129
DISTINCT. LIKE JORAM SAYS, 

548
00:24:07,129 --> 00:24:08,764
BECAUSE EACH OF THESE EYES MAY 

549
00:24:08,764 --> 00:24:09,865
IN FACT, HAVE A DIFFERENT THING 

550
00:24:09,865 --> 00:24:11,901
THEY ARE REALLY, REALLY 

551
00:24:11,901 --> 00:24:13,202
INTERESTED IN AND THEY NEED TO 

552
00:24:13,202 --> 00:24:17,173
CREATE A CIRCUIT THAT IS USED, 

553
00:24:17,173 --> 00:24:21,977
FOR EXAMPLE, IN CLIMATES NOT 

554
00:24:21,977 --> 00:24:25,614
PRESENT IN ZEBRAFISH, FOR 

555
00:24:25,614 --> 00:24:26,916
EXAMPLE, AND VICE VERSA. LET'S 

556
00:24:26,916 --> 00:24:29,618
START IN THE BEGINNING. I START 

557
00:24:29,618 --> 00:24:34,056
AT MY LAB IN WASH U AND ONE OF 

558
00:24:34,056 --> 00:24:34,924
MY FIRST STUDENTS AT THE NIH 

559
00:24:34,924 --> 00:24:37,560
KNEW I WAS INTERESTED IN THE 

560
00:24:37,560 --> 00:24:39,662
PROCESS OF MAKING CONNECTIONS. 

561
00:24:39,662 --> 00:24:41,997
ONE OF THAT IS -- ONE IMPORTANT 

562
00:24:41,997 --> 00:24:44,166
QUESTION WAS TO ASK, WHAT ARE 

563
00:24:44,166 --> 00:24:49,972
THE FACTORS THAT SHAPE THE 

564
00:24:49,972 --> 00:24:51,440
DENDRYTIC UNIVERSE OF THE CELLS.

565
00:24:51,440 --> 00:24:53,309
IMAGINE IF THEY ARE NOT GROWING 

566
00:24:53,309 --> 00:24:55,144
OR MAY NOT BE MAKING THE RIGHT 

567
00:24:55,144 --> 00:24:56,912
PARTNERSHIPS. SO MOST OF THE 

568
00:24:56,912 --> 00:24:58,380
TIME, OR AT LEAST RIGHT UP TO 

569
00:24:58,380 --> 00:25:02,051
THAT STAGE YOU LOOK AT DENDRITIC

570
00:25:02,051 --> 00:25:04,420
DEVELOPMENT BY FIXING TISSUE AT 

571
00:25:04,420 --> 00:25:06,088
DIFFERENT TIME, LABELING THE 

572
00:25:06,088 --> 00:25:07,756
CELL, IF YOU COULD, AND SAY THIS

573
00:25:07,756 --> 00:25:10,092
IS WHAT IT LOOKS LIKE NOW AND 

574
00:25:10,092 --> 00:25:11,827
FEW DAYS LATER AND FROM THAT 

575
00:25:11,827 --> 00:25:13,963
DEDUCE PERHAPS THE CELLULAR 

576
00:25:13,963 --> 00:25:19,768
INTERACTIONS THAT REGULATE THE 

577
00:25:19,768 --> 00:25:21,136
DENRITIC ORGANIZATION. BUT HAD 

578
00:25:21,136 --> 00:25:23,739
MUCH BETTER IDEA. I DON'T LIKE 

579
00:25:23,739 --> 00:25:26,275
LOOKING AT DEAD TISSUE VERY 

580
00:25:26,275 --> 00:25:28,544
LONG. IT IS ALL STATIC. IT IS 

581
00:25:28,544 --> 00:25:35,451
LIKE A SOCCER GAME. YOU DON'T 

582
00:25:35,451 --> 00:25:37,253
KNOW HOW THE GOAL HAPPENED. 

583
00:25:37,253 --> 00:25:39,421
LARRY CAME OUT WITH A GENE GUN, 

584
00:25:39,421 --> 00:25:40,990
A BALLISTIC DEVICE WHERE YOU CAN

585
00:25:40,990 --> 00:25:43,559
COAT LITTLE PARTICLES AND SHOOT 

586
00:25:43,559 --> 00:25:45,594
IT GENTLY ON A PIECE OF RETINA 

587
00:25:45,594 --> 00:25:47,296
THAT'S BEEN ISOLATED, PUT IT IN 

588
00:25:47,296 --> 00:25:49,632
AN INCUBATOR, GET IT TO BED. 

589
00:25:49,632 --> 00:25:51,934
THEN THE NEXT DAY, IF YOU DO 

590
00:25:51,934 --> 00:25:53,869
YOUR COATING WITH D.N.A. THAT 

591
00:25:53,869 --> 00:25:56,672
ENCODES FOR THE JELLY FISH GREEN

592
00:25:56,672 --> 00:25:58,173
PROTEIN, YOU CAN ACTUALLY GET 

593
00:25:58,173 --> 00:26:00,976
THE CELLS TO GLOW. YOU CAN DO 

594
00:26:00,976 --> 00:26:02,778
TIME-LAPSED. THE RETINA STAYS 

595
00:26:02,778 --> 00:26:04,780
HAPPY IN THE DISH FOR DAYS. THIS

596
00:26:04,780 --> 00:26:06,749
IS JUST NOT TO EMPHASIZE 

597
00:26:06,749 --> 00:26:08,717
ANYTHING OTHER THAN FROM THESE 

598
00:26:08,717 --> 00:26:11,854
TYPES OF APPROACHES WE CAN LOOK 

599
00:26:11,854 --> 00:26:14,023
AT, FOR EXAMPLE, FORMATION OF A 

600
00:26:14,023 --> 00:26:16,258
NEW PROCESS OR ELIMINATION OF 

601
00:26:16,258 --> 00:26:19,261
SOME PROCESS OVER TIME. THE 

602
00:26:19,261 --> 00:26:21,063
BOTTOM LINE FROM THESE STUDIES 

603
00:26:21,063 --> 00:26:24,300
WE RELEASE OF GLUTAMATE WAS 

604
00:26:24,300 --> 00:26:26,735
IMPORTANT IN GETTING NEW 

605
00:26:26,735 --> 00:26:29,238
PROCESSES TO STABILIZE AND ALSO 

606
00:26:29,238 --> 00:26:31,674
FOR THE EYEBALL TO GROW. THAT 

607
00:26:31,674 --> 00:26:34,043
LED TO A NEW SERIES OF 

608
00:26:34,043 --> 00:26:37,413
EXPERIMENTS WHERE WE DECIDED TO 

609
00:26:37,413 --> 00:26:39,481
USE THE GENE GUN TO NOT ONLY 

610
00:26:39,481 --> 00:26:42,084
SHOOT THIS IN BUT MONITOR THE 

611
00:26:42,084 --> 00:26:43,085
ACTIVITY WITHIN THE CELL. OFTEN 

612
00:26:43,085 --> 00:26:48,691
WHAT WE NORMALLY DO IS WE USE 

613
00:26:48,691 --> 00:26:52,628
ELECTRODES AND YOU 

614
00:26:52,628 --> 00:26:55,597
PATCH-CLAMPING ONTO A CELL AND 

615
00:26:55,597 --> 00:27:00,469
YOU WOULD LISTEN. THIS IS A 

616
00:27:00,469 --> 00:27:02,304
CELL-ATTACHED PACK SO YOU DON'T 

617
00:27:02,304 --> 00:27:03,939
BREAK ANYTHING. WE KNEW IF WE 

618
00:27:03,939 --> 00:27:06,008
PUT A HOLE IN THE MEMBRANE THE 

619
00:27:06,008 --> 00:27:07,376
CELL WAS PROBABLY GOING TO DIE 

620
00:27:07,376 --> 00:27:09,678
AFTER SOME PERIOD OF TIME. WE 

621
00:27:09,678 --> 00:27:11,580
MAY DO THINGS LIKE WASH OUT 

622
00:27:11,580 --> 00:27:13,582
CONTENTS IN THE CELL BODY THAT 

623
00:27:13,582 --> 00:27:14,316
MIGHT ACTUALLY BE IMPORTANT FOR 

624
00:27:14,316 --> 00:27:16,518
SOME OF THE PROCESSES WE ARE 

625
00:27:16,518 --> 00:27:19,088
INTERESTED IN. SO CHRISTIAN HAD 

626
00:27:19,088 --> 00:27:25,461
THIS IDEA WITH PATRONELL AND BEN

627
00:27:25,461 --> 00:27:27,930
VANGAN AT SOMETHING WE WERE ALL 

628
00:27:27,930 --> 00:27:31,800
AT. COATING THE PARTICLES NOT 

629
00:27:31,800 --> 00:27:35,571
WITH PARSE BUT CALCIUM INDICATED

630
00:27:35,571 --> 00:27:38,240
DYES. IT WORKED. IN SOME CASES 

631
00:27:38,240 --> 00:27:39,375
THE BULLET WENT IN AND OVER TIME

632
00:27:39,375 --> 00:27:42,978
IN THE TIME LAPSE YOU CAN DETECT

633
00:27:42,978 --> 00:27:48,684
CHANGES IN FLOUR  FLOURESCENCE 

634
00:27:48,684 --> 00:27:50,252
BUT THERE WERE LITTLE FLASHES 

635
00:27:50,252 --> 00:27:53,889
YOU MIGHT SEE IN THE DENDRITES. 

636
00:27:53,889 --> 00:28:00,162
AND YOU PROBABLY SEE BLINKIES 

637
00:28:00,162 --> 00:28:05,434
OVER TIME. SO WHEN YOU CORRELATE

638
00:28:05,434 --> 00:28:08,637
THIS YOU CAN MONITOR THE VOLT 

639
00:28:08,637 --> 00:28:10,372
CHANGES SAME TIME AS CALCIUM 

640
00:28:10,372 --> 00:28:11,774
CHANGES. YOU SEE WHEN YOU HAVE 

641
00:28:11,774 --> 00:28:13,675
THE BIG FLASH YOU WILL HAVE A 

642
00:28:13,675 --> 00:28:16,345
BURST OF SPIKES, THESE ACTION 

643
00:28:16,345 --> 00:28:18,147
POTENTIALS BUT THE LITTLE LOCAL 

644
00:28:18,147 --> 00:28:20,249
EVENTS, THERE WAS NO CHANGE IN 

645
00:28:20,249 --> 00:28:21,650
VOLTAGE. SO THERE ARE DIFFERENT 

646
00:28:21,650 --> 00:28:23,318
CALCIUM EVENTS. WE FOUND WHEN 

647
00:28:23,318 --> 00:28:27,589
YOU PUT THE RETINA, THIS IS A 

648
00:28:27,589 --> 00:28:30,626
CHICK RETINA IN VITRO, THAT 

649
00:28:30,626 --> 00:28:34,029
STOPS THE CALCIUM-INDUCED, 

650
00:28:34,029 --> 00:28:36,365
RELEASE FROM THE CELLULAR CELLS,

651
00:28:36,365 --> 00:28:42,471
THE GANGLION WOULD SHRINK OVER 

652
00:28:42,471 --> 00:28:44,973
TIME SO IT IS IMPORTANT FOR 

653
00:28:44,973 --> 00:28:47,376
ESSENTIALLY KEEPING THE 

654
00:28:47,376 --> 00:28:49,978
DENDRITES STABLE. WE COULD 

655
00:28:49,978 --> 00:28:52,414
RESCUE FROM SHRINKING BY PUTTING

656
00:28:52,414 --> 00:28:55,584
BACK LOCALLY BY SHINING 

657
00:28:55,584 --> 00:28:57,419
ESSENTIALLY UV SPOT IN CELLS IN 

658
00:28:57,419 --> 00:28:59,988
WHICH WE HAVE LOADED NOT ONLY 

659
00:28:59,988 --> 00:29:02,758
WITH CALCIUM INDICATOR BUT WITH 

660
00:29:02,758 --> 00:29:05,627
SOMETHING CALLED KACHE CALCIUM 

661
00:29:05,627 --> 00:29:07,529
WHERE THIS CHEMICALLY RELEASES 

662
00:29:07,529 --> 00:29:10,566
UPON ABSORPTION OF UV LIGHT. SO 

663
00:29:10,566 --> 00:29:13,135
THIS REGION HERE WE FOUND VERY 

664
00:29:13,135 --> 00:29:16,805
LITTLE RETRACTION WHEN YOU PUT 

665
00:29:16,805 --> 00:29:18,373
THE LET THAT OUTSIDE REGION 

666
00:29:18,373 --> 00:29:21,176
WHERE THERE IS NO UNCAGING OF 

667
00:29:21,176 --> 00:29:23,045
CALCIUM, YOU SEE RETRACTION. SO 

668
00:29:23,045 --> 00:29:24,379
THAT TOGETHER SUGGESTS THESE 

669
00:29:24,379 --> 00:29:29,251
LOCAL EVENTS STABILIZE DENDRIT E

670
00:29:29,251 --> 00:29:30,452
DEVELOPMENT. THERE WAS A LOT 

671
00:29:30,452 --> 00:29:31,787
GOING ON. I WON'T GO THROUGH 

672
00:29:31,787 --> 00:29:34,456
ALL. BUT THE CALCIUM EVENTS 

673
00:29:34,456 --> 00:29:37,526
OCCUR WHEN PRE-SYNAPTIC CONTACT 

674
00:29:37,526 --> 00:29:39,828
THE GANGLION CELLS AND IT IS 

675
00:29:39,828 --> 00:29:41,497
THAT CONTACT THAT TRIGGERS 

676
00:29:41,497 --> 00:29:42,831
CALCIUM AND KEEPS THAT 

677
00:29:42,831 --> 00:29:44,066
CONNECTION TOGETHER, OKAY? IF 

678
00:29:44,066 --> 00:29:48,203
YOU WANT TO READ MORE, IT IS IN 

679
00:29:48,203 --> 00:29:51,473
A PAPER IN 2002. WE ALSO 

680
00:29:51,473 --> 00:29:53,142
REALIZED THAT WHILE WE CAN WATCH

681
00:29:53,142 --> 00:30:00,015
ACTIVITY AND EVEN MONITOR DEN 

682
00:30:00,015 --> 00:30:02,084
DRITIC CHANGES LIVE IN A DISH 

683
00:30:02,084 --> 00:30:03,585
THINGS COULD BE DIFFERENT IN THE

684
00:30:03,585 --> 00:30:04,987
ANIMAL THEMSELVES. IT WAS 

685
00:30:04,987 --> 00:30:08,390
IMPORTANT TO WATCH DENDRITIC 

686
00:30:08,390 --> 00:30:12,361
GROWTH INVIVO. THIS IS WHERE YOU

687
00:30:12,361 --> 00:30:14,229
RECOGNIZE THIS CHARACTER. JEFF 

688
00:30:14,229 --> 00:30:15,831
JOINED THE LAB. HE IS EXCITED 

689
00:30:15,831 --> 00:30:18,300
ABOUT USING ZEBRAFISH, SO HE 

690
00:30:18,300 --> 00:30:21,403
HELPED SET UP THE ZEBRAFISH. THE

691
00:30:21,403 --> 00:30:22,738
TANKS HADN'T EVEN ARRIVED THEN 

692
00:30:22,738 --> 00:30:25,908
IN THE LAB. WE HAVE EXPERIMENTS 

693
00:30:25,908 --> 00:30:28,677
FROM ANIMALS FROM THE LAB AT 

694
00:30:28,677 --> 00:30:31,680
UCSF AND JEFF AND ERIC MADE LOTS

695
00:30:31,680 --> 00:30:38,620
OF PLASMIDS SO MAKE TRANSGENIC 

696
00:30:38,620 --> 00:30:40,088
ANIMALS WHOSE EYES GLOW, 

697
00:30:40,088 --> 00:30:42,090
DEPENDING ON THE PROTEINS. YOU 

698
00:30:42,090 --> 00:30:45,327
CAN DO TIME LAPSE. HERE ARE 

699
00:30:45,327 --> 00:30:47,596
EMACRIN CELLS, MIGRATING, 

700
00:30:47,596 --> 00:30:50,766
GETTING TO THE FORMING IPL AND 

701
00:30:50,766 --> 00:31:00,842
FORMING ITS PROCESSES. AND NIGHT

702
00:31:00,842 --> 00:31:03,712
I THINK IT WAS JEFF WHERE HE 

703
00:31:03,712 --> 00:31:05,714
MONITORED THE GROWTH AND SAW IT 

704
00:31:05,714 --> 00:31:08,817
DEVELOPED TWO EYEBALLS 

705
00:31:08,817 --> 00:31:11,086
SEQUENTIALLY OVER TIME SO THE 

706
00:31:11,086 --> 00:31:17,326
INVIVO EXPERIMENTS. FROM THE 

707
00:31:17,326 --> 00:31:21,029
GANGLION CELL, DEPENDS UP TO 

708
00:31:21,029 --> 00:31:23,599
THAT TIME MOST THOUGHT THESE 

709
00:31:23,599 --> 00:31:29,571
DENDRITIC EYEBALLS BECOME K

710
00:31:29,571 --> 00:31:31,974
CALCIFIED FROM A WAY THAT IS 

711
00:31:31,974 --> 00:31:33,942
DIFFUSE. THIS IS EVERYWHERE THEN

712
00:31:33,942 --> 00:31:36,545
SOMETHING COMES ALONG, SHAPES 

713
00:31:36,545 --> 00:31:38,714
IT, CUTS UP A THE BRANCHES AND 

714
00:31:38,714 --> 00:31:41,149
BECOMES STRATIFIED. JEFF AND HIS

715
00:31:41,149 --> 00:31:43,185
COLLEAGUES DISCOVERED WAYS OF 

716
00:31:43,185 --> 00:31:46,989
THE DENDRITIC LAMINATION OF 

717
00:31:46,989 --> 00:31:48,390
THESE CELLS AND THE EXAMPLE I 

718
00:31:48,390 --> 00:31:50,626
GAVE YOU THAT YOU JUST SAW HERE,

719
00:31:50,626 --> 00:31:52,127
WAS ONE AND YOU CANNOT REALLY 

720
00:31:52,127 --> 00:31:53,829
KNOW THIS HAPPENED BECAUSE YOU 

721
00:31:53,829 --> 00:31:55,797
CANNOT FOLLOW THE SAME CELL IN A

722
00:31:55,797 --> 00:31:58,467
DISH OVER TIME. OR FIXED RETINA 

723
00:31:58,467 --> 00:32:00,435
AT DIFFERENT TIMES AND THEN 

724
00:32:00,435 --> 00:32:02,170
INFER WHAT HAPPENED BECAUSE IT 

725
00:32:02,170 --> 00:32:04,006
IS NOT THE SAME CELL ANYMORE. SO

726
00:32:04,006 --> 00:32:06,341
THE INVIVO IMAGING WAS CRITICAL 

727
00:32:06,341 --> 00:32:08,377
IN TELLING US THERE ARE MORE 

728
00:32:08,377 --> 00:32:19,087
WAYS THAN ONE FOR DEN DRITES TO 

729
00:32:20,589 --> 00:32:21,156
ACQUIRE SHAPE AND LAMINATION TO 

730
00:32:21,156 --> 00:32:21,790
MAKE CONNECTIONS TO THE 

731
00:32:21,790 --> 00:32:24,026
PRE-SYNAPTIC CELLS. WE DECIDED 

732
00:32:24,026 --> 00:32:27,663
WHILE WE LOVE DENDRITES WE 

733
00:32:27,663 --> 00:32:29,431
WANTED TO THINK ABOUT 

734
00:32:29,431 --> 00:32:31,366
CONNECTIONS. YOU NEED TO MAP UP 

735
00:32:31,366 --> 00:32:35,037
THE CONNECTIVITY AT THE LEVEL OF

736
00:32:35,037 --> 00:32:40,042
SYNAP

737
00:32:40,042 --> 00:32:42,344
SYNAPSES. WE MOVED FROM ZEBRA 

738
00:32:42,344 --> 00:32:44,346
FISH -- STILL HAD ZEBRAFISH BUT 

739
00:32:44,346 --> 00:32:46,615
TO THE MOUSE RETINA WHERE WE CAN

740
00:32:46,615 --> 00:32:49,318
MAKE TRANSGENIC ANIMALS TO LABEL

741
00:32:49,318 --> 00:32:52,954
PARTICULAR TYPES OF CELLS OR USE

742
00:32:52,954 --> 00:32:58,160
GENETIC TOOLS TO -- FOR EXAMPLE 

743
00:32:58,160 --> 00:32:58,894
NEUROTRANSMISSION IN CERTAIN 

744
00:32:58,894 --> 00:33:01,997
CELL TYPES. SO WE LOVE THE GENE 

745
00:33:01,997 --> 00:33:04,566
GUN AT THIS STAGE, YOU CAN TELL.

746
00:33:04,566 --> 00:33:06,501
MORE MACHINE GUNNERS ON THE 

747
00:33:06,501 --> 00:33:08,437
RIGHT. JOSH AND DAN USED THE 

748
00:33:08,437 --> 00:33:12,174
MACHINE GUN TO LABEL NOT ONLY 

749
00:33:12,174 --> 00:33:16,044
THE DENDRITIC EYEBALLS OF THE 

750
00:33:16,044 --> 00:33:18,714
GANGLION CELLS BUT THOSE 

751
00:33:18,714 --> 00:33:23,085
REPRESENT POST-SEN NAP TICK 95 

752
00:33:23,085 --> 00:33:24,920
INFUSED THE YELLOW PROTEIN. IF 

753
00:33:24,920 --> 00:33:28,290
YOU SHOOT THAT IN A TRANSGENIC 

754
00:33:28,290 --> 00:33:30,425
ANIMAL WHERE SOME BIPOLAR CELLS 

755
00:33:30,425 --> 00:33:34,863
ARE LABEL EXPRESSING DIFFERENT 

756
00:33:34,863 --> 00:33:37,566
PROTEIN COLOR, THIS IS THE WHOLE

757
00:33:37,566 --> 00:33:39,968
RANGE OF COLORS FROM THIS JELLY 

758
00:33:39,968 --> 00:33:46,375
FISH MUTATED. THIS IS CORAL. YOU

759
00:33:46,375 --> 00:33:48,043
CAN IDENTIFY THE LOCATIONS WHERE

760
00:33:48,043 --> 00:33:50,412
THEY ACTUALLY CONTACT. THE 

761
00:33:50,412 --> 00:33:54,116
LITTLE DOTS ARE PS95 SUGGESTIVE 

762
00:33:54,116 --> 00:33:57,753
OF AN ACTUAL SYNAPSE AT THIS 

763
00:33:57,753 --> 00:34:04,693
SITE. USING THESE MAPPING TOOLS,

764
00:34:04,693 --> 00:34:06,395
FLOURESCENCE MAPPING, DANIEL DID

765
00:34:06,395 --> 00:34:08,163
THE STUDY WHERE WE NOT ONLY 

766
00:34:08,163 --> 00:34:12,000
LABEL SOME OF THE NEURONS BUT 

767
00:34:12,000 --> 00:34:16,171
SILENCE THROUGH THE EXPRESSION 

768
00:34:16,171 --> 00:34:17,606
OF TETANUS TOXIN WHICH DIFFUSE 

769
00:34:17,606 --> 00:34:22,811
AND TRANSMITORS CAN'T GET 

770
00:34:22,811 --> 00:34:25,313
RELEASED. THESE EXPRESS THIS 

771
00:34:25,313 --> 00:34:27,416
TETANUS TOXIN ONLY ON BIPOLAR 

772
00:34:27,416 --> 00:34:29,351
EXPRESS THE TETANUS TOXIN. WITH 

773
00:34:29,351 --> 00:34:32,754
E LOOK AT A TYPE POST-SYNAPTIC 

774
00:34:32,754 --> 00:34:37,959
TO THE CELLS. YOU SAW THE ALPHA 

775
00:34:37,959 --> 00:34:40,128
GANGLION AND LOTS OF DOTS AT 25 

776
00:34:40,128 --> 00:34:42,731
AND IN THE MOUSE. BUT IN THE TNT

777
00:34:42,731 --> 00:34:44,733
MOUSE WHERE THERE IS LITTLE NO 

778
00:34:44,733 --> 00:34:46,101
TRANSMISSION FROM THE BIPOLARS 

779
00:34:46,101 --> 00:34:52,207
TO THE GANGLION, FAR FEWER PS95 

780
00:34:52,207 --> 00:34:54,743
AND FEWER SYNAPSES. IF YOU 

781
00:34:54,743 --> 00:34:55,410
QUANTIFY, IT IS ABOUT THE SAME 

782
00:34:55,410 --> 00:34:57,779
BUT DON'T INCREASE -- TNT DOES 

783
00:34:57,779 --> 00:34:59,748
NOT INCREASE IN THE WILD TYPE. 

784
00:34:59,748 --> 00:35:03,518
SO THAT TELLS YOU BIPOLAR CELL 

785
00:35:03,518 --> 00:35:04,586
TRANSMISSION IS IMPORTANT FOR 

786
00:35:04,586 --> 00:35:06,788
GETTING THE SYNAPSES MEET WITH 

787
00:35:06,788 --> 00:35:13,128
THE RETINAL GANGLION CELLS. 

788
00:35:13,128 --> 00:35:14,863
HARVARD WENT UNSTEP FORWARD. 

789
00:35:14,863 --> 00:35:21,036
INSTEAD OF WIPING PEOPLE BY THE 

790
00:35:21,036 --> 00:35:22,971
WHOLE POPULATION, HE DID A FEW. 

791
00:35:22,971 --> 00:35:24,773
THIS IS EXPRESSING TETANUS 

792
00:35:24,773 --> 00:35:26,641
TOXIN, THIS ISN'T. HE ASKED THE 

793
00:35:26,641 --> 00:35:27,776
QUESTION, IF YOU HAVE TWO 

794
00:35:27,776 --> 00:35:30,445
NEIGHBORS WHO ARE SHARING A 

795
00:35:30,445 --> 00:35:33,415
POST-SYNAPTIC CELL HERE AND ONE 

796
00:35:33,415 --> 00:35:35,717
IS INACTIVE AND THE OTHER IS 

797
00:35:35,717 --> 00:35:40,822
NOT, IS THIS INACTIVE ONE LOSE 

798
00:35:40,822 --> 00:35:44,493
SYNAPSES, CONTACTING WITH 

799
00:35:44,493 --> 00:35:46,261
GANGLION CELL AND NEIGHBOR TAKE 

800
00:35:46,261 --> 00:35:48,597
ADVANTAGE OF THE SILENCE AND 

801
00:35:48,597 --> 00:35:50,699
GRAB THE SYNAPSE S? IS THERE A 

802
00:35:50,699 --> 00:35:52,033
COMPETITION? A WINNER AND LOSER,

803
00:35:52,033 --> 00:35:56,304
AS YOU SEE IN A NEUROMUSCULAR 

804
00:35:56,304 --> 00:35:58,073
JUNCTION OF DEVELOPMENT. TURNS 

805
00:35:58,073 --> 00:36:01,042
OUT INACTIVE BIPOLAR CELL MAKES 

806
00:36:01,042 --> 00:36:03,979
FEWER SYNAPSES, JUST A NUMBER, 

807
00:36:03,979 --> 00:36:06,581
COMPARED TO AN ACTIVE NEIGHBOR 

808
00:36:06,581 --> 00:36:07,415
SHARING THE SAME PIECE OF 

809
00:36:07,415 --> 00:36:09,684
DENDRITE. BUT WHAT WE SEE IS 

810
00:36:09,684 --> 00:36:13,021
THIS. WE DON'T SEE TAKEOVER .

811
00:36:13,021 --> 00:36:15,023
THE NEIGHBOR IS NOT 

812
00:36:15,023 --> 00:36:16,892
OPPORTUNE ISTIC. WHAT IT HAS, IT

813
00:36:16,892 --> 00:36:19,194
WILL KEEP IT, WHILE SILENCED 

814
00:36:19,194 --> 00:36:23,565
NEIGHBOR IS LOSING SYNAPSES AND 

815
00:36:23,565 --> 00:36:27,068
ITS MORPHOLO DPV Y DOESN'T 

816
00:36:27,068 --> 00:36:31,072
CHANGE. IF YOU LOOK AT THE PF95,

817
00:36:31,072 --> 00:36:33,508
SPOTS, THEY ARE LARGER, 

818
00:36:33,508 --> 00:36:35,877
DENDRITES WHEN CONTACTED BY UP 

819
00:36:35,877 --> 00:36:38,113
ACTIVE BIPOLAR CELL. THIS IS 

820
00:36:38,113 --> 00:36:46,054
TYPICAL, JEFF WILL TELL YOU, 

821
00:36:46,054 --> 00:36:48,757
COMOSTATIC RESPONSE. IS BETTER, 

822
00:36:48,757 --> 00:36:50,859
PUTTING MORE RECEPTORS, BUT OF 

823
00:36:50,859 --> 00:36:52,193
COURSE NOTHING GOING ON THERE. 

824
00:36:52,193 --> 00:36:54,996
SO YOU CAN SEE LOCAL CHANGES AT 

825
00:36:54,996 --> 00:36:56,565
THE LEVEL OF INDIVIDUAL 

826
00:36:56,565 --> 00:36:58,333
SYNAPSES. SO TRANSMISSION FROM 

827
00:36:58,333 --> 00:37:00,101
BIPOLAR CELL S IS IMPORTANT. 

828
00:37:00,101 --> 00:37:01,469
DANIEL PUT TOGETHER THIS 

829
00:37:01,469 --> 00:37:03,004
WONDERFUL SUMMARY SLIDE THAT I 

830
00:37:03,004 --> 00:37:07,075
BORROWED FROM HIM. IN WILD TYPE 

831
00:37:07,075 --> 00:37:09,044
YOU MIGHT GET X NUMBER WHEN YOU 

832
00:37:09,044 --> 00:37:11,146
ARE SILENCE THE BIPOLAR 

833
00:37:11,146 --> 00:37:12,814
INDIVIDUALLY OR AS A POPULATION,

834
00:37:12,814 --> 00:37:14,549
YOU WILL STILL GET A DECREASE IN

835
00:37:14,549 --> 00:37:19,054
NUMBER OF SYNAPSES MADE THOSE 

836
00:37:19,054 --> 00:37:21,222
SILENT BIPOLAR CELLS, OKAY. 

837
00:37:21,222 --> 00:37:24,125
DANIEL WENT ON USING THE CRX 

838
00:37:24,125 --> 00:37:26,461
NEWTON, WHERE FULL RECEPTORS ARE

839
00:37:26,461 --> 00:37:28,897
NOT FUNCTIONING NORMALLY, 

840
00:37:28,897 --> 00:37:31,099
BIPOLAR ACTIVITY IS UP. AND IF 

841
00:37:31,099 --> 00:37:32,734
VIRUS HAS BECOME MORE ACTIVE, 

842
00:37:32,734 --> 00:37:34,102
THEY ACTUALLY MACK MORE 

843
00:37:34,102 --> 00:37:37,505
SYNAPSES. SO KIND OF LIKE A 

844
00:37:37,505 --> 00:37:39,441
DIAL. DEPENDING ON BIPOLAR 

845
00:37:39,441 --> 00:37:41,676
ACTIVITY, THE BIPOLAR CELL WILL 

846
00:37:41,676 --> 00:37:44,412
MAKE MORE OR LESS SYNAPSES WITH 

847
00:37:44,412 --> 00:37:45,847
GANGLION CELL. THIS IS GOOD TO 

848
00:37:45,847 --> 00:37:47,515
KNOW. ESPECIALLY IF YOU WANT TO 

849
00:37:47,515 --> 00:37:49,484
REWIRE SOMETHING YOU MIGHT WANT 

850
00:37:49,484 --> 00:37:50,919
TO ASK WHAT IMPORTANT IS 

851
00:37:50,919 --> 00:37:54,322
ACTIVITY OF PRE-SYNAPTIC TO 

852
00:37:54,322 --> 00:37:56,458
POST-SYNAPTIC CELL TO MAKE THE 

853
00:37:56,458 --> 00:37:59,561
RIGHT NUMBER OF SYNAPSES. WELL, 

854
00:37:59,561 --> 00:38:01,997
AFTER GOING THROUGH ALL THE " WE

855
00:38:01,997 --> 00:38:04,132
MUST DO LIVE " STUFF TO FOLLOW 

856
00:38:04,132 --> 00:38:06,801
AND SEE HOW IT HAPPENS INVIVO, 

857
00:38:06,801 --> 00:38:08,703
MOST RECENTLY WENT TO LOOK AT 

858
00:38:08,703 --> 00:38:11,272
FIXED TISSUE. IT IS LIKE WHAT 

859
00:38:11,272 --> 00:38:13,308
HAPPENED HERE? WELL, TURNS OUT 

860
00:38:13,308 --> 00:38:17,879
THERE ARE CERTAIN THINGS THAT 

861
00:38:17,879 --> 00:38:20,582
EVEN WITH THE MOST WONDERFUL 

862
00:38:20,582 --> 00:38:21,416
FLORESCENTS YOU CAN'T BE CERTAIN

863
00:38:21,416 --> 00:38:25,854
YOU ARE LOOKING AT A SYNAPSE. 

864
00:38:25,854 --> 00:38:27,288
YOU TYPE SOMETHING, EXPRESS IT, 

865
00:38:27,288 --> 00:38:29,958
GOES TO THE SITE. IT IS A GOOD 

866
00:38:29,958 --> 00:38:31,192
INDICATION BUT HOW DO YOU KNOW 

867
00:38:31,192 --> 00:38:32,293
THAT EVERYONE IS 

868
00:38:32,293 --> 00:38:38,967
SYNAPSE ED?ENTER THE BEST WAY IS

869
00:38:38,967 --> 00:38:42,203
ELECTRO MICROSCOPY TO THE LEVEL 

870
00:38:42,203 --> 00:38:52,380
OF NAN NANOMETER. THAT WITH 

871
00:38:52,380 --> 00:38:53,682
SCANNING, THE THANKS GROUP 

872
00:38:53,682 --> 00:38:55,083
DEVELOPED. YOU KNOW KEVIN 

873
00:38:55,083 --> 00:38:56,851
BRICKMAN BECAUSE HE WAS HERE, 

874
00:38:56,851 --> 00:38:59,621
HAD INSTRMENTAL PART IN GETTING 

875
00:38:59,621 --> 00:39:02,357
THE ZERO BLOCK PHASE SCANNING EM

876
00:39:02,357 --> 00:39:04,192
METHOD FOR US ALL TO USE. WE 

877
00:39:04,192 --> 00:39:07,162
HAVE BEEN DOING A LOT OF THIS. 

878
00:39:07,162 --> 00:39:09,197
PARTLY BECAUSE THERE ARE SOME 

879
00:39:09,197 --> 00:39:11,266
TISSUES WE CANNOT DO LIVE OR 

880
00:39:11,266 --> 00:39:13,334
INVIVO IMAGING, SUCH AS IN 

881
00:39:13,334 --> 00:39:16,538
HUMANS. SO WE DECIDED EM WAS 

882
00:39:16,538 --> 00:39:17,806
IMPORTANT. THIS IS ESSENTIALLY 

883
00:39:17,806 --> 00:39:20,241
HOW IT WORKS. YOU CAN DO ALL 

884
00:39:20,241 --> 00:39:22,410
THESE RECONSTRUCTIONS. MANUALLY 

885
00:39:22,410 --> 00:39:25,246
IN THIS CASE. AFTER YOU HAVE CUT

886
00:39:25,246 --> 00:39:26,381
SECTIONS, SCANNED THE SURFACE, 

887
00:39:26,381 --> 00:39:28,683
THAT SECTION IS THROWN AWAY. GET

888
00:39:28,683 --> 00:39:30,618
THE NEXT SECTION AND BUILD IT 

889
00:39:30,618 --> 00:39:35,457
OVER TIME. THE MOVIE YOU JUST 

890
00:39:35,457 --> 00:39:37,358
SAW WAS ESSENTIALLY SERIES OF 

891
00:39:37,358 --> 00:39:38,326
IMAGES BROUGHT TOGETHER WITH 

892
00:39:38,326 --> 00:39:40,695
THIS METHOD, RECONSTRUCTED BY 

893
00:39:40,695 --> 00:39:42,831
HAND. YOU SEE TWO BIPOLAR CELLS,

894
00:39:42,831 --> 00:39:45,500
THE DENDRITES ARE THE BIPOLAR 

895
00:39:45,500 --> 00:39:49,904
CELLS AND RIBBONS HERE AND PHOTO

896
00:39:49,904 --> 00:39:55,243
RECEPTORS AND MIDGET BIPOLAR 

897
00:39:55,243 --> 00:39:59,280
CELLS IN THE HUMAN. IT IS 

898
00:39:59,280 --> 00:40:03,051
POSSIBLE TO CORRELATE IMAGING 

899
00:40:03,051 --> 00:40:07,422
WITH ZERO EM. WE HAVE LABELED IN

900
00:40:07,422 --> 00:40:09,924
THIS CONDITION THE GANGL ION 

901
00:40:09,924 --> 00:40:13,695
CELLS THESE BRIGHT PATCHES, TYPE

902
00:40:13,695 --> 00:40:16,197
WITH YFP TRANSGENIC ANIMAL. TAKE

903
00:40:16,197 --> 00:40:21,369
THE IMAGE, NOW WHERE THESE ARE. 

904
00:40:21,369 --> 00:40:22,704
YOU CAN TAKE THE BLOCK AND 

905
00:40:22,704 --> 00:40:24,038
RECONSTRUCT PROCESSES. WE KNOW 

906
00:40:24,038 --> 00:40:27,509
IT WAS IN CELL BODY OF A 

907
00:40:27,509 --> 00:40:32,981
GANGLION CELL. THESE ARE AMOCRON

908
00:40:32,981 --> 00:40:35,517
MAKING GABA CYST AT THAT SITE. 

909
00:40:35,517 --> 00:40:38,419
WE STUDY TO STUDY DEVELOPMENT OF

910
00:40:38,419 --> 00:40:40,321
SYNAPSES OF CELLS BUT I DON'T 

911
00:40:40,321 --> 00:40:43,525
HAVE TIME TO TALK ABOUT THAT 

912
00:40:43,525 --> 00:40:46,394
MUCH TODAY. SO WE WILL ALL TALK 

913
00:40:46,394 --> 00:40:49,864
ABOUT CHOOSING PARTNERS AND 

914
00:40:49,864 --> 00:40:51,366
MAKING APPROPRIATE SYNAPSES, 

915
00:40:51,366 --> 00:40:53,301
MOSTLY USING EM METHODS RIGHT 

916
00:40:53,301 --> 00:40:55,103
NOW. I WANT TO TALK ABOUT THE 

917
00:40:55,103 --> 00:40:57,338
CONNECTIVITY, WITH I IS REALLY 

918
00:40:57,338 --> 00:40:59,774
TO CONNECT IS HOW YOU FIND AND 

919
00:40:59,774 --> 00:41:01,409
CHOOSE RIGHT PARTNERS, THE 

920
00:41:01,409 --> 00:41:03,044
SELECTION HERE AND HOW DO YOU 

921
00:41:03,044 --> 00:41:04,679
MAKE RIGHT NUMBER OF CONNECTIONS

922
00:41:04,679 --> 00:41:06,915
EVEN IF THE PARTNERS OF YOUR 

923
00:41:06,915 --> 00:41:09,617
CHOICE. THIS IS A GRADUATE 

924
00:41:09,617 --> 00:41:11,186
STUDENT SO M & Ms IN CASE
YOU 

925
00:41:11,186 --> 00:41:13,621
ARE NOT SURE. THIS PARTICULAR 

926
00:41:13,621 --> 00:41:15,924
STUDENT LIKES RED AND BLUE M
& 

927
00:41:15,924 --> 00:41:20,595
Ms. THAT IS ALL SHE PREFERS, 

928
00:41:20,595 --> 00:41:23,031
LEAVES THE REST AND YOU SAY WHAT

929
00:41:23,031 --> 00:41:26,234
MOLECULE IS MAKING HER DO THAT? 

930
00:41:26,234 --> 00:41:31,172
SHE IS VERY HAPPY WITH. THE 

931
00:41:31,172 --> 00:41:33,708
OTHER PART IS WHAT PART OF THIS 

932
00:41:33,708 --> 00:41:35,410
SYNAPSE EXCITE, HOW DO YOU PUT 

933
00:41:35,410 --> 00:41:36,911
EACH OF THESE SYNAPSES TOGETHER?

934
00:41:36,911 --> 00:41:39,547
THERE IS A SPECIALIZED ANATOMY. 

935
00:41:39,547 --> 00:41:41,449
FOR EXAMPLE, THE DIET SYNAPSE IN

936
00:41:41,449 --> 00:41:43,151
THE RETINA. THEY ARE ALSO 

937
00:41:43,151 --> 00:41:45,353
GETTING THE RIGHT RECEPTORS AND 

938
00:41:45,353 --> 00:41:47,322
PRO TYPES AT SYNAPSES IN THE 

939
00:41:47,322 --> 00:41:50,225
RIGHT LOCATIONS, WHICH IN THIS 

940
00:41:50,225 --> 00:41:53,695
CASE WE CAN LABEL UP WITH AM 

941
00:41:53,695 --> 00:41:57,398
MEAN KNOW CHEMISTRY OR TYPE THEM

942
00:41:57,398 --> 00:42:00,768
WITH TRANSGENIC ANIMALS. I WON'T

943
00:42:00,768 --> 00:42:02,971
TALK ABOUT THESE SYNAPSES, A LOT

944
00:42:02,971 --> 00:42:05,974
OF FOCUS ON WIRES. I WILL STUDY 

945
00:42:05,974 --> 00:42:08,710
ON THE OUTER RETINA, ASKING THE 

946
00:42:08,710 --> 00:42:11,613
QUESTION HOW DO YOU CHOOSE 

947
00:42:11,613 --> 00:42:12,447
PARTNER S? MAYBE I WON'T BE 

948
00:42:12,447 --> 00:42:14,015
ANSWERING HOW BUT THE FACT YOU 

949
00:42:14,015 --> 00:42:16,351
NEED TO CHOOSE PARTNERS OR MAYBE

950
00:42:16,351 --> 00:42:18,786
SOME DON'T NEED PART NERS AND 

951
00:42:18,786 --> 00:42:20,922
TALK ABOUT THE INNER RETINA FOR 

952
00:42:20,922 --> 00:42:21,890
THIS PARTICULAR SYNAPSE, WHICH 

953
00:42:21,890 --> 00:42:23,691
WE WILL GET TO IN A MINUTE. 

954
00:42:23,691 --> 00:42:26,461
BECAUSE ANAN IS HERE, I DECIDED 

955
00:42:26,461 --> 00:42:29,497
TO PUT THIS LITTLE SNIP PET IN 

956
00:42:29,497 --> 00:42:31,566
TO TALK ABOUT ROD AND CONE 

957
00:42:31,566 --> 00:42:32,300
CONNECTIVITY. I THINK THIS IS 

958
00:42:32,300 --> 00:42:34,335
THE FIRST TIME YOU ARE SEEING 

959
00:42:34,335 --> 00:42:36,537
IT. ABOUT THE FIRST TIME I AM 

960
00:42:36,537 --> 00:42:40,008
TOO. SO WE WILL WORK ON THIS 

961
00:42:40,008 --> 00:42:42,043
TOGETHER. WE ALL KNOW ROD 

962
00:42:42,043 --> 00:42:44,145
BIPOLAR LOVE RODS. THEIR PRIMARY

963
00:42:44,145 --> 00:42:45,580
CONNECTIONS ARE ROD. THEY IN 

964
00:42:45,580 --> 00:42:47,548
MOUSE RETINA CAN CONTACT SOME 

965
00:42:47,548 --> 00:42:49,017
CONES TOO BUT THEY REALLY LIKE 

966
00:42:49,017 --> 00:42:50,752
RODS. THE CONVERSE IS TRUE FOR 

967
00:42:50,752 --> 00:42:53,054
THE CONE BIPOLARS WHICH LOVES 

968
00:42:53,054 --> 00:42:56,891
CONES AND VERY FEW RODS. WELL, 

969
00:42:56,891 --> 00:42:59,327
WE KNOW ALSO THE ROD KIND 

970
00:42:59,327 --> 00:43:00,495
SYNAPSES DIFFER SOMEWHAT. THE 

971
00:43:00,495 --> 00:43:04,232
ROD SPHERE IS SMALLER, THE CONE 

972
00:43:04,232 --> 00:43:07,035
IS MORE TRIANGULAR, HAVE MORE 

973
00:43:07,035 --> 00:43:11,072
SITES THE CONE BIPOLAR CELLS. 

974
00:43:11,072 --> 00:43:14,042
BOTH ARE INVITING SYNAPSES IN 

975
00:43:14,042 --> 00:43:19,314
THAT THEY PUT LITTLE DENDRATIC 

976
00:43:19,314 --> 00:43:21,683
TIPS IN THE SPIR RI KAL OPPOSITE

977
00:43:21,683 --> 00:43:26,721
THE RUB BO RIBBON SIDE WHERE 

978
00:43:26,721 --> 00:43:28,189
RELEASE OCCURS. THE MANY STUDIES

979
00:43:28,189 --> 00:43:30,224
FOR EXAMPLE WHERE YOU DON'T HAVE

980
00:43:30,224 --> 00:43:31,993
MANY CONE, LOSS OF CONES FOR 

981
00:43:31,993 --> 00:43:34,696
EXAMPLE, EITHER TO DEVELOPMENT 

982
00:43:34,696 --> 00:43:37,231
OR DISEASE, THE UN-BIPOLAR CELLS

983
00:43:37,231 --> 00:43:41,302
CAN CONTACT THE RODS. THEY DO. 

984
00:43:41,302 --> 00:43:43,604
THEY DON'T EN DODGE NATE ALL THE

985
00:43:43,604 --> 00:43:45,873
TIME. IN CASE YOU LOSE RODS THE 

986
00:43:45,873 --> 00:43:47,942
ROD BIPOLAR CELL NOT HAVING MY 

987
00:43:47,942 --> 00:43:52,680
RODS WILL CONTACT MORE CONES. SO

988
00:43:52,680 --> 00:43:55,249
CHI IN MY LAB WAS NOT INTERESTED

989
00:43:55,249 --> 00:43:58,853
SO MUCH IN RODS AND CONES BUT A 

990
00:43:58,853 --> 00:44:00,855
RETINA WITH CONE-FREE, NO RODS 

991
00:44:00,855 --> 00:44:04,659
AND LOTS OF CONES. THIS IS THE 

992
00:44:04,659 --> 00:44:07,562
RD7 RETINA, THE S CONE MUTANT, 

993
00:44:07,562 --> 00:44:10,398
FOR EXAMPLE. AND THE NRL 

994
00:44:10,398 --> 00:44:12,033
KNOCK-OUT. YOU ALL KNOW ABOUT 

995
00:44:12,033 --> 00:44:15,870
NRL BECAUSE ANON IS HERE AND 

996
00:44:15,870 --> 00:44:16,637
DISCOVERED HOW IMPORTANT THIS 

997
00:44:16,637 --> 00:44:19,240
GENE IS IN REGULATING ROD FATE. 

998
00:44:19,240 --> 00:44:24,178
THIS IS CONE FATE. IF THERE IS 

999
00:44:24,178 --> 00:44:25,079
ANYTHING WRONG, BASICALLY TELL 

1000
00:44:25,079 --> 00:44:27,582
ME LATER. IF YOU GET RID OF NRL,

1001
00:44:27,582 --> 00:44:30,318
YOU DON'T MAKE RODS. IT IS 

1002
00:44:30,318 --> 00:44:31,919
INCREDIBLE. THIS IS A REALLY 

1003
00:44:31,919 --> 00:44:33,488
IMPORTANT GENE. AT THE SAME 

1004
00:44:33,488 --> 00:44:35,690
TIME, YOU DON'T LOSE THOSE 

1005
00:44:35,690 --> 00:44:38,026
CELLS, THEY ALL BECOME CONE-LIKE

1006
00:44:38,026 --> 00:44:42,897
CELLS. NOT JUST CONE-LIKE BUT S 

1007
00:44:42,897 --> 00:44:47,668
CONE-LIKE CELLS. ASSOCIATED WITH

1008
00:44:47,668 --> 00:44:50,671
CONES RATHER THAN WITH RODS. IF 

1009
00:44:50,671 --> 00:44:52,540
YOU COMPARE AND LOOK AT WHAT 

1010
00:44:52,540 --> 00:44:54,042
THESE CONE TRENDS ARE COMPARED 

1011
00:44:54,042 --> 00:44:56,644
TO CONES, WHAT DO THEY HAVE IN 

1012
00:44:56,644 --> 00:45:04,719
COMMON, THEY HAVE IN COMMON SOME

1013
00:45:04,719 --> 00:45:10,792
HISTOLOGY, WAVELENGTH AT 360. 

1014
00:45:10,792 --> 00:45:12,460
KNOW NR23 STANDS FOR NRL, IF YOU

1015
00:45:12,460 --> 00:45:19,033
LOOK AT THE MU TIGS, WH -- MUTA 

1016
00:45:19,033 --> 00:45:20,968
YOU MAKE CONES. THINGS ARE A 

1017
00:45:20,968 --> 00:45:23,071
LITTLE MORE COMPLICATED IN THE 

1018
00:45:23,071 --> 00:45:24,872
RD7. YOU NOT ONLY MAKE THESE 

1019
00:45:24,872 --> 00:45:27,041
CONE-LIKE CELLS BUT YOU ALSO 

1020
00:45:27,041 --> 00:45:31,212
HAVE A HYBRID, A ROD/CONE HYBRID

1021
00:45:31,212 --> 00:45:34,549
WITH RODOPSIN IN IT AND MANY 

1022
00:45:34,549 --> 00:45:36,984
THINGS. IT WILL BE MANY OF THOSE

1023
00:45:36,984 --> 00:45:38,886
THINGS ANON AND I WILL TALK 

1024
00:45:38,886 --> 00:45:40,688
ABOUT LATER , THE GENE PROFILES 

1025
00:45:40,688 --> 00:45:42,523
THAT MAKES THESE CELLS THE WAY 

1026
00:45:42,523 --> 00:45:44,192
THEY ARE. BASICALLY SHE ASKED 

1027
00:45:44,192 --> 00:45:45,793
WHAT HAPPENS TO BIPOLAR CELLS 

1028
00:45:45,793 --> 00:45:47,628
WHEN FACED WITH JUST CONES AND 

1029
00:45:47,628 --> 00:45:51,999
CONE TRENDS IN THE NRL KNOCK-OUT

1030
00:45:51,999 --> 00:45:55,369
OR THIS THREE PHOTO RECEPTOR 

1031
00:45:55,369 --> 00:45:59,340
TYPES IN THE RD7? FIRST OF ALL 

1032
00:45:59,340 --> 00:46:03,044
COULD WE FIND AND DIFFERENT 

1033
00:46:03,044 --> 00:46:05,379
TYPES OF RECEPTORS. YOU CAN SEE 

1034
00:46:05,379 --> 00:46:07,181
RODS AND CONES LOOK DIFFERENT. 

1035
00:46:07,181 --> 00:46:09,684
CONES MULTIPLE RIBBONS, RODS 

1036
00:46:09,684 --> 00:46:12,854
SINGLE, VARIOUS ARE TRIANGULAR, 

1037
00:46:12,854 --> 00:46:17,091
THESE ARE BULBOUS. IN NRL CONE 

1038
00:46:17,091 --> 00:46:18,960
LOOK MORE LIKE RODS BUT HAVE 

1039
00:46:18,960 --> 00:46:20,495
MULTIPLE RIBBONS AND THEIR CONES

1040
00:46:20,495 --> 00:46:23,231
A LITTLE ALTERED SLIGHTLY MAYBE 

1041
00:46:23,231 --> 00:46:25,066
NOT QUITE TRIANGULAR BECAUSE 

1042
00:46:25,066 --> 00:46:27,034
THERE'S SO MANY OF THESE THAT 

1043
00:46:27,034 --> 00:46:28,369
ARE PUSHING EVERYBODY AROUND. 

1044
00:46:28,369 --> 00:46:30,838
YOU SEE THESE TWO TYPES. THESE 

1045
00:46:30,838 --> 00:46:33,608
ARE 0EM RECONSTRUCTIONS AND IN 

1046
00:46:33,608 --> 00:46:36,043
THE RD7 YOU SEE THE HYBRID. THE 

1047
00:46:36,043 --> 00:46:39,914
CONE TRENDS, WHICH IS MORE LIKE 

1048
00:46:39,914 --> 00:46:42,884
-- SO SOMETHING IN BETWEEN. THEN

1049
00:46:42,884 --> 00:46:45,119
THE NORMAL CONES BECAUSE THEY 

1050
00:46:45,119 --> 00:46:49,991
COME -- THEY MEET FROM CONE PER 

1051
00:46:49,991 --> 00:46:53,561
CURSOR LINEAGE INSTEAD OF THE 

1052
00:46:53,561 --> 00:46:55,696
ROD. IF YOU LOOK AT THE 

1053
00:46:55,696 --> 00:47:02,537
RECEPTORS, THIS IS THE NORMAL 

1054
00:47:02,537 --> 00:47:05,940
TRID ARRANGEMENT. THEY MAKE LOTS

1055
00:47:05,940 --> 00:47:08,042
OF SYNAPSES BUT SOME ARE NOT 

1056
00:47:08,042 --> 00:47:10,311
VERY NOVEL. THEY DON'T HAVE IN 

1057
00:47:10,311 --> 00:47:14,916
THIS CASE BIPOLAR BUT NO HORIZON

1058
00:47:14,916 --> 00:47:18,386
CELLS COAT IN THAT SITE. SOME 

1059
00:47:18,386 --> 00:47:20,588
THESE SYNAPSES ARE NOT NORMAL 

1060
00:47:20,588 --> 00:47:22,056
BUT MAKE LOTS OF SYNAPSES WITH 

1061
00:47:22,056 --> 00:47:25,359
CONE TRENDS. SHE MAPPED OUT THE 

1062
00:47:25,359 --> 00:47:26,827
CONNECTIVITY. THE FIRST IS IF 

1063
00:47:26,827 --> 00:47:29,964
YOU LOOK AT THE CONE PRECURSOR 

1064
00:47:29,964 --> 00:47:35,403
DERIVED CELLS, SO IN RD7 AND THE

1065
00:47:35,403 --> 00:47:37,038
KNOCK-OUT AND NOT WILD TYPE THIS

1066
00:47:37,038 --> 00:47:40,441
IS WHAT LOOKS LIKE. YOU CAN SEE 

1067
00:47:40,441 --> 00:47:43,144
ROD BIPOLAR DON'T LIKE CONE-LIKE

1068
00:47:43,144 --> 00:47:44,245
CELLS. WILD TYPE WE KNEW 

1069
00:47:44,245 --> 00:47:46,080
ALREADY. MAYBE A LITTLE BIT IN 

1070
00:47:46,080 --> 00:47:48,115
OUR KNOCK-OUT, THERE IS SOME, 

1071
00:47:48,115 --> 00:47:50,985
BUT IN THE RD7 IT IS PRETTY MUCH

1072
00:47:50,985 --> 00:47:54,589
WILD TYPE LEVEL. BUT IN THE ROD 

1073
00:47:54,589 --> 00:47:56,857
PRECURSOR DERIVED PATHWAY THAT 

1074
00:47:56,857 --> 00:48:01,229
LINEAGE THAT REQUIRES THE NRL 

1075
00:48:01,229 --> 00:48:04,165
AND 2E3 WE SEE A COMBINATION OF 

1076
00:48:04,165 --> 00:48:08,703
EFFECTS. WE SEE THE ROD BIPOLAR 

1077
00:48:08,703 --> 00:48:10,538
CENTS DON'T MIND CONE TRENDS BUT

1078
00:48:10,538 --> 00:48:20,381
IN RD7 THE ROD BIPOLAR PREFER 

1079
00:48:20,381 --> 00:48:23,351
MORE THAN CONE TRENDS IN THE 

1080
00:48:23,351 --> 00:48:25,786
KNOCK-OUT SO THIS SEEMS REALLY 

1081
00:48:25,786 --> 00:48:28,356
CONFUSING BUT WE CAN THINK ABOUT

1082
00:48:28,356 --> 00:48:30,891
IT IN OTHER WAYS IN A WHILE. I 

1083
00:48:30,891 --> 00:48:33,661
SAID TO GI, WHAT IS COMING AND 

1084
00:48:33,661 --> 00:48:35,096
WHAT IS DIFFERENT IN THESE TWO 

1085
00:48:35,096 --> 00:48:37,331
CONDITIONS THAT CAUSE THE ROD 

1086
00:48:37,331 --> 00:48:38,866
BIPOLAR AND CONE BIPOLAR TO 

1087
00:48:38,866 --> 00:48:42,270
SELECT PARTICULAR PARTNERS AND 

1088
00:48:42,270 --> 00:48:48,676
NOT OTHERS? ROD IS GOING TO 

1089
00:48:48,676 --> 00:48:50,678
CONNECT WITH BIPOLARS AND SAID 

1090
00:48:50,678 --> 00:48:55,249
NO IT IS NOT THE MORPHOLOGY BUT 

1091
00:48:55,249 --> 00:48:59,620
THERE ARE GENES EXPRESSED IN 

1092
00:48:59,620 --> 00:48:59,954
TH

1093
00:48:59,954 --> 00:49:02,890
THIS CLUSTER THAT RODS RECOGNIZE

1094
00:49:02,890 --> 00:49:05,459
OR USE THIS THESE ARE MORE 

1095
00:49:05,459 --> 00:49:06,060
PREFERRED PARTNERS AND THIS 

1096
00:49:06,060 --> 00:49:09,697
ISN'T THERE. EITHER THE TWO CONE

1097
00:49:09,697 --> 00:49:10,831
TRENDS ARE DIFFERENT OR THERE IS

1098
00:49:10,831 --> 00:49:12,400
A CHOICE IN SENSE OF THE RD 

1099
00:49:12,400 --> 00:49:14,535
WHERE THE BIPOLARS CAN GO FOR 

1100
00:49:14,535 --> 00:49:16,771
MORE ROD-LIKE RECEPTORS COMPARED

1101
00:49:16,771 --> 00:49:20,741
TO A CONE-LIKE ONE. A CHOICE OR 

1102
00:49:20,741 --> 00:49:22,910
SOMETHING DIFFERENT. SO ANON 

1103
00:49:22,910 --> 00:49:24,712
HELP ME LATER AND FIGURE OUT 

1104
00:49:24,712 --> 00:49:26,213
WHAT THE MOLECULAR DIFFERENCES 

1105
00:49:26,213 --> 00:49:29,717
MIGHT BE. THE IMPORTANT THING IS

1106
00:49:29,717 --> 00:49:31,786
CONE BIPOLARS. THIS IS ONE TYPE,

1107
00:49:31,786 --> 00:49:35,156
CONE TYPE 6. NRL AND RD7 THESE 

1108
00:49:35,156 --> 00:49:37,525
CONE BIPOLAR CELLS, HERE IS THE 

1109
00:49:37,525 --> 00:49:39,560
WILD TYPE. THEY NORMALLY DON'T 

1110
00:49:39,560 --> 00:49:42,563
WANT RODS BUT IN NRL THEY ARE 

1111
00:49:42,563 --> 00:49:45,132
QUITE HAPPY WITH THE CONVERTED 

1112
00:49:45,132 --> 00:49:48,736
CONES OR THE CONES THEMSELVES. 

1113
00:49:48,736 --> 00:49:52,073
IN THE RD7 THEY PREFER THE 

1114
00:49:52,073 --> 00:49:54,141
CONES, SOME CONE TRENDS BUT NOT 

1115
00:49:54,141 --> 00:49:57,078
THE HYBRID. SO AGAIN I THINK WE 

1116
00:49:57,078 --> 00:50:00,147
CAN USE THESE TWO ESSENTIALLY 

1117
00:50:00,147 --> 00:50:04,785
MODEL SYSTEMS TO BEGIN TO TEASE 

1118
00:50:04,785 --> 00:50:06,153
APART COLLECTION OF MOLECULES 

1119
00:50:06,153 --> 00:50:08,689
THAT HAVE RODS TO ROD BIPOLARS 

1120
00:50:08,689 --> 00:50:10,825
AND CONE BIPOLARS JUST PICKING 

1121
00:50:10,825 --> 00:50:13,427
UP CONES. IF YOU KNEW WHAT THESE

1122
00:50:13,427 --> 00:50:14,862
MOLECULES ARE, NOT JUST SO MUCH 

1123
00:50:14,862 --> 00:50:15,963
FOR UNDERSTANDING DEVELOPMENT 

1124
00:50:15,963 --> 00:50:18,733
BUT MIGHT BE USEFUL IN TERMS OF 

1125
00:50:18,733 --> 00:50:20,735
SETTING UP WHAT COULD BE 

1126
00:50:20,735 --> 00:50:23,204
IMPORTANT DATA ON REPAIR. 

1127
00:50:23,204 --> 00:50:25,072
LEAVING THE BIPOLARS JUST TO 

1128
00:50:25,072 --> 00:50:26,474
TELL YOU THAT THE HORIZON CELLS 

1129
00:50:26,474 --> 00:50:29,310
WHICH ALSO ARE PARTNERS AT THIS 

1130
00:50:29,310 --> 00:50:31,178
SYNAPSE NORMALLY HAVE DENDRITES 

1131
00:50:31,178 --> 00:50:35,449
AND AXONS AND DENDRITES NORMALLY

1132
00:50:35,449 --> 00:50:39,186
LIKE CONES AND AXONS LIKE RODSN.

1133
00:50:39,186 --> 00:50:44,191
A CONE FULL RETINA YOU HAVE THE 

1134
00:50:44,191 --> 00:50:45,292
DENDRITE SEPARATED BUT 

1135
00:50:45,292 --> 00:50:47,461
CONNECTIVITY ARE NO LONGER 

1136
00:50:47,461 --> 00:50:53,601
SPECIFIC. THE AXONAL AND 

1137
00:50:53,601 --> 00:50:55,102
DENDRITIC CONTRAST RODS AND 

1138
00:50:55,102 --> 00:50:58,105
CONES IN NRL AND NO RODS LEFT. 

1139
00:50:58,105 --> 00:51:01,742
SO QUICK SUMMARY, BASICALLY WHAT

1140
00:51:01,742 --> 00:51:03,444
WE FOUND IS THAT IN THE WILD 

1141
00:51:03,444 --> 00:51:08,082
TYPE YOU HAVE KIND OF THIS 

1142
00:51:08,082 --> 00:51:11,318
CONDITION. IN THE NRL KNOCKOUT I

1143
00:51:11,318 --> 00:51:12,553
DEMONSTRATED ROD BIPOLAR CONNECT

1144
00:51:12,553 --> 00:51:14,922
TO BOTH TYPE OF RECEPTORS SO 

1145
00:51:14,922 --> 00:51:16,323
WILL THE CONE BIPOLAR CELL BUT 

1146
00:51:16,323 --> 00:51:20,094
IN THE RD7 THE ROD BIPOLAR 

1147
00:51:20,094 --> 00:51:21,896
PREFERS THE HYBRID OVER THE CONE

1148
00:51:21,896 --> 00:51:23,764
TRENDS AND THE CONE BIPOLAR 

1149
00:51:23,764 --> 00:51:26,967
CELLS PREFER THE CONE-LIKE CELLS

1150
00:51:26,967 --> 00:51:28,536
COMPARED TO THE ROD HYBRID. 

1151
00:51:28,536 --> 00:51:30,471
THERE IS SOME SELECTIVITY. WE 

1152
00:51:30,471 --> 00:51:32,873
JUST DO NOT KNOW EXACTLY WHAT 

1153
00:51:32,873 --> 00:51:34,575
THESE ARE. THAT IS WHAT I JUST 

1154
00:51:34,575 --> 00:51:36,944
SAID. BUT I THINK IF YOU ARE 

1155
00:51:36,944 --> 00:51:38,679
COMPLETELY CONFUSED AT THE 

1156
00:51:38,679 --> 00:51:39,947
WIRING, DON'T WORRY ABOUT IT AT 

1157
00:51:39,947 --> 00:51:42,783
ALL. I THINK THE KEY HERE FOR ME

1158
00:51:42,783 --> 00:51:45,753
WAS NOT WHO PICKED WHO BUT YOU 

1159
00:51:45,753 --> 00:51:48,789
CAN EXPRESS IN FOUR RECEPTORS 

1160
00:51:48,789 --> 00:51:50,391
ALONE THAT.  WILL DICTATE 

1161
00:51:50,391 --> 00:51:51,959
SYNAPTIC PARTNERSHIP WITH THE 

1162
00:51:51,959 --> 00:51:53,994
BIPOLAR CELLS. THAT ALONE FOR 

1163
00:51:53,994 --> 00:51:55,029
REPAIR, THAT WOULD BE REALLY 

1164
00:51:55,029 --> 00:51:56,764
GOOD TO KNOW. YOU WON'T HAVE TO 

1165
00:51:56,764 --> 00:51:59,733
AFFECT TWO SITES OF THE 

1166
00:51:59,733 --> 00:52:01,469
PARTNERSHIP IN ORDER TO FORM 

1167
00:52:01,469 --> 00:52:03,037
THAT HANDSHAKE. YOU JUST HAVE TO

1168
00:52:03,037 --> 00:52:04,939
DO SOMETHING WITH THE LEFT HAND 

1169
00:52:04,939 --> 00:52:05,906
AND THEY WILL KNOW WHICH RIGHT 

1170
00:52:05,906 --> 00:52:10,244
HAND TO GO FOR. MAKE SENSE? VERY

1171
00:52:10,244 --> 00:52:12,580
QUICKLY THE MOLECULAR 

1172
00:52:12,580 --> 00:52:15,049
INTERACTIONS, FOR SURE, IS 

1173
00:52:15,049 --> 00:52:16,584
IMPORTANT. AT LEAST LET'S LOOK 

1174
00:52:16,584 --> 00:52:19,019
AT WHAT HAPPENED TO THE -- 

1175
00:52:19,019 --> 00:52:21,121
BASICALLY DEVELOPMENT OF THESE 

1176
00:52:21,121 --> 00:52:22,857
SYNAPSES FOR RODS AND CONES FOR 

1177
00:52:22,857 --> 00:52:27,061
EXPERIENCE AND WE FIND IF YOU 

1178
00:52:27,061 --> 00:52:29,530
DOT REAR THE ANIMAL THE DOT 

1179
00:52:29,530 --> 00:52:30,431
REARING DIMINISHES THE CONE BUT 

1180
00:52:30,431 --> 00:52:34,969
NOT THE ROD. THESE ARE RAWLINGS 

1181
00:52:34,969 --> 00:52:36,504
YOU ARE FAMILIAR WITH SO CONE 

1182
00:52:36,504 --> 00:52:38,138
RESPONSE IS DOWN BUT NOT WITH 

1183
00:52:38,138 --> 00:52:46,480
THE ROD. THAT IS BECAUSE IN THAT

1184
00:52:46,480 --> 00:52:49,049
AT THE FULL RECEPTOR SYNAPSE 

1185
00:52:49,049 --> 00:52:51,986
APPEARS TO BE NORMAL. THESE ARE 

1186
00:52:51,986 --> 00:52:53,654
JUST STAINING FOR THESE 

1187
00:52:53,654 --> 00:52:55,723
RECEPTORS BUT MUCH LOWER IN 

1188
00:52:55,723 --> 00:52:58,359
CONES THEMSELVES. SO THESE 

1189
00:52:58,359 --> 00:53:01,762
RECEPTORS SEEM TO NOT CLUSTER OR

1190
00:53:01,762 --> 00:53:04,198
HANG AROUND IN DOT REARING IN 

1191
00:53:04,198 --> 00:53:08,102
CONE PATHWAY BUT NOT IN THE ROD.

1192
00:53:08,102 --> 00:53:11,105
YOU DON'T NEED LIKE TO KEEP THAT

1193
00:53:11,105 --> 00:53:12,473
ROD SORT OF SYNAPSED TOGETHER. 

1194
00:53:12,473 --> 00:53:14,642
SO LET'S SEE. I HAVE LITTLE MORE

1195
00:53:14,642 --> 00:53:16,477
TIME. SO LET'S TALK NOW, MOVE 

1196
00:53:16,477 --> 00:53:18,746
FROM OUTER RETINA TO INNER 

1197
00:53:18,746 --> 00:53:20,948
RETINA. I PROMISE WE CAN TALK A 

1198
00:53:20,948 --> 00:53:23,884
LITTLE ABOUT THE OUTPUT OF THE 

1199
00:53:23,884 --> 00:53:25,419
CELLS. HERELY STICK TO THE ROD 

1200
00:53:25,419 --> 00:53:27,721
PATHWAY WHERE I WILL TALK A 

1201
00:53:27,721 --> 00:53:31,692
LITTLE ABOUT ROD BIPOLAR 

1202
00:53:31,692 --> 00:53:35,829
CONNECTING WITH ENOCRN CELL AND 

1203
00:53:35,829 --> 00:53:38,732
PARTICULARLY THIS PICTURE, WHAT 

1204
00:53:38,732 --> 00:53:41,402
THEY LOOK LIKE, WHAT WILL HAS 

1205
00:53:41,402 --> 00:53:42,937
INJECTED. YOU WILL SEE CELLS 

1206
00:53:42,937 --> 00:53:46,106
MAKE CONNECTIONS PRETTY MUCH 

1207
00:53:46,106 --> 00:53:48,442
WITH THE ROD BIPOLAR CELL 

1208
00:53:48,442 --> 00:53:52,413
FORMING SYNAPSE WITH TWO TYPES 

1209
00:53:52,413 --> 00:53:55,549
OF AMMOCRYNS AND INTERESTING NOT

1210
00:53:55,549 --> 00:53:58,218
DRIVEN BY ROD BIPOLAR CELL BUT 

1211
00:53:58,218 --> 00:54:00,988
DRIVES IT ALSO. RESIP ROW KAL 

1212
00:54:00,988 --> 00:54:02,122
FEEDBACK FOR THIS INHIBITION. 

1213
00:54:02,122 --> 00:54:06,126
THAT OCCURS AT THESE DOTS. I 

1214
00:54:06,126 --> 00:54:07,361
WILL TALK ABOUT THIS SYNAPSE. 

1215
00:54:07,361 --> 00:54:09,830
WITH E KNOW THE SELECTIVITY OF 

1216
00:54:09,830 --> 00:54:13,534
THE A17 FOR ROD BIPOLAR CELLS IS

1217
00:54:13,534 --> 00:54:16,070
HERE. SO THIS IS A17 CELL. ALL 

1218
00:54:16,070 --> 00:54:18,639
THESE -- SORRY, ALL THESE YELLOW

1219
00:54:18,639 --> 00:54:21,508
DOTS ARE WHERE BUTONS ARE WITH 

1220
00:54:21,508 --> 00:54:24,144
THE ROD BIPOLAR CELLS, MAKE VERY

1221
00:54:24,144 --> 00:54:28,115
FEW CONE, BIPOLAR OR GANGLION 

1222
00:54:28,115 --> 00:54:29,883
CELL SYNAPSES. THE FEW THEY MAKE

1223
00:54:29,883 --> 00:54:33,887
WITH THE BIPOLAR CELL, WHICH 

1224
00:54:33,887 --> 00:54:36,223
THERE ARE MANY TYPES OF THESE. 

1225
00:54:36,223 --> 00:54:38,392
SO WE KNOW THIS A17 REFERENCE 

1226
00:54:38,392 --> 00:54:40,027
FOR ROD BIPOLAR CELLS APPEAR 

1227
00:54:40,027 --> 00:54:42,429
EARLY IN DEVELOPMENT. YOU CAN 

1228
00:54:42,429 --> 00:54:45,032
SEE POST 9 AND 10 ARE MUCH OF 

1229
00:54:45,032 --> 00:54:45,933
THE SYNAPSES ARE HERE AND THEY 

1230
00:54:45,933 --> 00:54:50,204
ARE YELLOW WITH THE ROD BIPOLAR 

1231
00:54:50,204 --> 00:54:51,705
CELLS. OKAY. SO SELECTIVITY 

1232
00:54:51,705 --> 00:54:54,274
EARLY. WHAT HAPPENS IF YOU KILL 

1233
00:54:54,274 --> 00:54:56,910
OFF THESE ROD BIPOLAR CELLS? WE 

1234
00:54:56,910 --> 00:55:02,449
USE A METHOD WHERE WE EXPRESS ON

1235
00:55:02,449 --> 00:55:08,122
BIPOLAR CELLS. NOT ONLY ROD BUT 

1236
00:55:08,122 --> 00:55:10,924
SOME ON BUT NOT OFF BIPOLARS 

1237
00:55:10,924 --> 00:55:13,260
USING LINE WHERE EXPRESSED 

1238
00:55:13,260 --> 00:55:18,432
TOXIN. THEY EXPRESS YELLOW IN 

1239
00:55:18,432 --> 00:55:19,867
PROTEIN BUT IF NOT REMOVED THERE

1240
00:55:19,867 --> 00:55:24,238
IS NO DTA EXPRESSION. SO THESE 

1241
00:55:24,238 --> 00:55:26,140
FLUORESCENT AREAS ARE TERMINALS 

1242
00:55:26,140 --> 00:55:29,309
WITH I ARE FINE AND DOT AREAS 

1243
00:55:29,309 --> 00:55:31,378
WHERE THERE ARE BIPOLARS AND 

1244
00:55:31,378 --> 00:55:33,714
EXPRESSING DTA. WE DO 

1245
00:55:33,714 --> 00:55:36,183
FLUORESCENT IMAGING, USE THE 

1246
00:55:36,183 --> 00:55:38,285
LASER TO MAKE MOUNTS TO FIND 

1247
00:55:38,285 --> 00:55:41,355
EXACTLY THESE BUTONS AGAIN UNDER

1248
00:55:41,355 --> 00:55:47,061
EM. FROM ONE OF THEM TRACE BACK 

1249
00:55:47,061 --> 00:55:49,296
A17AMACYN CELL. WHAT WE CAN SEE 

1250
00:55:49,296 --> 00:55:52,266
IF YOU DO NOT HAVE MANY ROD 

1251
00:55:52,266 --> 00:55:53,901
BIPOLAR CELLS DURING DEVELOPMENT

1252
00:55:53,901 --> 00:55:57,204
THE A17 MAKES MORE SYNAPSES WITH

1253
00:55:57,204 --> 00:55:58,906
THE COMBINED BIPOLAR CELLS. 

1254
00:55:58,906 --> 00:56:00,340
THERE IS SOME QUANTIFICATION 

1255
00:56:00,340 --> 00:56:04,178
HERE. MANY OF THESE COMBINED 

1256
00:56:04,178 --> 00:56:06,046
BIPOLAR CELLS, THERE ARE LOTS OF

1257
00:56:06,046 --> 00:56:11,151
OFF, SOME ON BUT WE KILLED SOME 

1258
00:56:11,151 --> 00:56:13,620
ON BIPOLAR CELLS. WITH THIS ONE 

1259
00:56:13,620 --> 00:56:17,524
STUDY WE THINK A17 RECOGNIZES 

1260
00:56:17,524 --> 00:56:20,461
THIS ROD BIPOLAR NOT BY CUES 

1261
00:56:20,461 --> 00:56:21,595
BECAUSE THEY ACTUALLY MAKE 

1262
00:56:21,595 --> 00:56:23,430
SYNAPSES TOO SO NOT RESTRICTED 

1263
00:56:23,430 --> 00:56:28,168
TO THIS LAYER. BUT THEY SEEM TO 

1264
00:56:28,168 --> 00:56:31,305
NEED SOME SELECTION CRITERIA 

1265
00:56:31,305 --> 00:56:36,310
WHICH HELP THEM GO FOR ROD 

1266
00:56:36,310 --> 00:56:37,244
BIPOLARS OVER CONE.

1267
00:56:37,244 --> 00:56:39,947
IF YOU DON'T HAVE ROD THEY WILL 

1268
00:56:39,947 --> 00:56:43,117
GO FOR THE CONE BIPOLAR EVEN THE

1269
00:56:43,117 --> 00:56:45,786
OFF CELLS. THIS CAN EXTEND ON 

1270
00:56:45,786 --> 00:56:47,254
AND OFF AND ROD AND CONE 

1271
00:56:47,254 --> 00:56:48,956
PATHWAY S SO WE THINK THERE 

1272
00:56:48,956 --> 00:56:51,592
MIGHT BE SOME SUPPRESSIVE SIGNAL

1273
00:56:51,592 --> 00:56:56,630
DISCOURAGING A17 FROM SYNAPSING 

1274
00:56:56,630 --> 00:56:58,632
WITH CONE BIPOLAR WITH ROD WHEN 

1275
00:56:58,632 --> 00:57:00,501
THEY MAKE CONTACT WITH ROD 

1276
00:57:00,501 --> 00:57:02,703
BIPOLAR CELLS.ENTERTHIS 

1277
00:57:02,703 --> 00:57:04,905
SUPPRESSIVE SIGNAL IS I FORM A 

1278
00:57:04,905 --> 00:57:06,774
HANDSHAKE, I KNOW WHO MAKING 

1279
00:57:06,774 --> 00:57:08,842
HANDSHAKE WITH, I DON'T NEED TO 

1280
00:57:08,842 --> 00:57:10,677
REACH OUT TO THE NEXT PERSON OR 

1281
00:57:10,677 --> 00:57:13,180
SOMETHING LIKE THAT. A STRONG 

1282
00:57:13,180 --> 00:57:15,215
HANDSHAKE. IF THAT HANDSHAKE 

1283
00:57:15,215 --> 00:57:16,550
ISN'T THERE, NEXT PERSON, GO 

1284
00:57:16,550 --> 00:57:21,855
DOWN TO THE NEXT ROW AND MICHAEL

1285
00:57:21,855 --> 00:57:24,591
IS NOT HERE SO GO TO THE NEXT 

1286
00:57:24,591 --> 00:57:25,959
PERSON FOR HANDSHAKE. MAY BE 

1287
00:57:25,959 --> 00:57:28,929
THAT THE TYPE ALLERGY. IS THIS 

1288
00:57:28,929 --> 00:57:33,767
SPECIAL A17 IN THE MOUSE OR LIKE

1289
00:57:33,767 --> 00:57:35,035
JORAM SAID COULD IT BE SOMEONE 

1290
00:57:35,035 --> 00:57:37,871
IN CROSS SPECIES OR DIFFERENT. 

1291
00:57:37,871 --> 00:57:40,340
SO IN ZEBRAFISH WE FOUND A 

1292
00:57:40,340 --> 00:57:42,676
SIMILAR PHENOMENON. INSTEAD OF 

1293
00:57:42,676 --> 00:57:46,079
BIPOLAR WE HAVE HORIZON CELL 

1294
00:57:46,079 --> 00:57:49,049
THAT LOVES UV CONES, THESE GUYS,

1295
00:57:49,049 --> 00:57:51,285
OVER BLUE CONES. DURING EARLY 

1296
00:57:51,285 --> 00:57:52,686
DEVELOPMENT THERE IS ALREADY A 

1297
00:57:52,686 --> 00:57:55,389
BIAS AND THAT BIAS GROWS AS THE 

1298
00:57:55,389 --> 00:57:57,724
ANIMAL GROWS UP AND MAKES MORE 

1299
00:57:57,724 --> 00:57:59,726
CONNECTIONS. LOVES UV, A LITTLE 

1300
00:57:59,726 --> 00:58:01,562
BLUE. BUT IN DEVELOPMENT IF YOU 

1301
00:58:01,562 --> 00:58:03,730
USE MUTANTS IN WHICH THERE ARE 

1302
00:58:03,730 --> 00:58:06,600
FEW UV CONES, NOW YOU ASK WHAT 

1303
00:58:06,600 --> 00:58:09,236
HAPPENS. THIS IS A SUMMARY OF 

1304
00:58:09,236 --> 00:58:11,538
THIS PAPER BY AKISHI. THIS 

1305
00:58:11,538 --> 00:58:14,141
HORIZON CELL WILL MAKE LOTS OF 

1306
00:58:14,141 --> 00:58:16,076
BLUE CONE INSTEAD. SO LIKES -- 

1307
00:58:16,076 --> 00:58:19,413
ALL NEURONS LIKE TO MAKE 

1308
00:58:19,413 --> 00:58:21,114
SYNAPSES, PLEASE MAKE A SYNAPSE.

1309
00:58:21,114 --> 00:58:23,550
THEN LIKE WHICH TYPE. SO IN 

1310
00:58:23,550 --> 00:58:25,252
ABSENCE OF PREFERRED PARTNER 

1311
00:58:25,252 --> 00:58:27,321
THIS HORIZON CELLS GO FOR THE 

1312
00:58:27,321 --> 00:58:29,456
SECONDARY ONE. IT DOESN'T GO FOR

1313
00:58:29,456 --> 00:58:33,093
RED GREEN, THOUGH. SO THERE IS 

1314
00:58:33,093 --> 00:58:40,167
STILL SOME SELECTIVE ONES, MAKE 

1315
00:58:40,167 --> 00:58:41,969
SELECTIVITY AS THEY MAKE THEIR 

1316
00:58:41,969 --> 00:58:44,037
CIRCUITRY DURING DEVELOPMENT. WE

1317
00:58:44,037 --> 00:58:45,772
DO NOT KNOW WHAT THIS BRICK 

1318
00:58:45,772 --> 00:58:49,443
MIGHT BE. IF THERE IS SUCH A 

1319
00:58:49,443 --> 00:58:51,511
BRICK. WHEN FEW ARE HERE MAKE 

1320
00:58:51,511 --> 00:58:52,913
PARTNERSHIP, DON'T DO BLUE. IT 

1321
00:58:52,913 --> 00:58:54,915
IS A CONCEPT I THINK IS WORTHY 

1322
00:58:54,915 --> 00:58:58,151
OF US THINKING MORE INDEPTH. 

1323
00:58:58,151 --> 00:58:59,519
BECAUSE WHEN YOU ALSO REWIRE 

1324
00:58:59,519 --> 00:59:00,587
SOMETHING WHAT ARE YOU 

1325
00:59:00,587 --> 00:59:04,024
PRESENTING TO THE NEW NEURONS 

1326
00:59:04,024 --> 00:59:06,560
THAT -- FROM THE NEW NEURON'S 

1327
00:59:06,560 --> 00:59:09,363
POINT OF VIEW WOULD BE 

1328
00:59:09,363 --> 00:59:10,864
ADVANTAGES FOR THE SURVIVING 

1329
00:59:10,864 --> 00:59:11,932
NEURONS , THE ONES THEY CONNECT 

1330
00:59:11,932 --> 00:59:15,002
TO IT. IF THEY NOW HAVE A 

1331
00:59:15,002 --> 00:59:16,470
CHOICE, HOW DO YOU HELP THEM 

1332
00:59:16,470 --> 00:59:18,138
MAKE THAT CHOICE? WE DIDN'T 

1333
00:59:18,138 --> 00:59:20,173
EXPECT THIS. WE THOUGHT IF IT IS

1334
00:59:20,173 --> 00:59:24,478
A MOLECULAR MATCHING, YOU HAVE 

1335
00:59:24,478 --> 00:59:26,246
MOLECULES A HERE, MOLECULES A 

1336
00:59:26,246 --> 00:59:28,181
AND RECOGNIZE SO YOU HAVE 

1337
00:59:28,181 --> 00:59:29,449
SELECTIVITY INDEED, A FANTASTIC 

1338
00:59:29,449 --> 00:59:31,118
WAY OF SELECTIVITY. THERE'S LOTS

1339
00:59:31,118 --> 00:59:34,021
OF EXAMPLES, ESPECIALLY IN 

1340
00:59:34,021 --> 00:59:35,255
INVERTEBRATE DEVELOPMENT AND IN 

1341
00:59:35,255 --> 00:59:38,125
THE INNER RETINA, JOSH'S GROUP. 

1342
00:59:38,125 --> 00:59:40,694
SO I JUST WANT TO EMPHASIZE 

1343
00:59:40,694 --> 00:59:43,964
LOSING SOME PARTNERS DOESN'T 

1344
00:59:43,964 --> 00:59:49,002
ALWAYS LEAD TO INCREASE 

1345
00:59:49,002 --> 00:59:53,674
CONNECTIVITY. THE OTHER AMACRYN 

1346
00:59:53,674 --> 00:59:56,343
MAKES CONNECTIVITY TO OFF 

1347
00:59:56,343 --> 00:59:59,713
BIPOLAR CELLS. IF YOU NOW REMOVE

1348
00:59:59,713 --> 01:00:01,248
ALL THE BIPOLAR CELLS THE 

1349
01:00:01,248 --> 01:00:02,916
PRIMARY PARTNER IS GONE. IT CAN 

1350
01:00:02,916 --> 01:00:06,787
STILL MAKE CONNECTIONS WITH 

1351
01:00:06,787 --> 01:00:08,422
GANGLION CELLS BUT VERY FEW. 

1352
01:00:08,422 --> 01:00:11,458
WHAT HAPPENS? INCREASED 

1353
01:00:11,458 --> 01:00:13,727
CONNECTIONS TO THE GANGLION CELL

1354
01:00:13,727 --> 01:00:16,096
OR NOT? SO CLAIR WHEN IN THE LAB

1355
01:00:16,096 --> 01:00:19,833
LOOKED AT THE STRUCTURES, THE 

1356
01:00:19,833 --> 01:00:22,636
OUTPUT SITE OF THE CELL. WE CAN 

1357
01:00:22,636 --> 01:00:26,373
IMAGE AND SEE WHAT THEY LOOK 

1358
01:00:26,373 --> 01:00:27,841
LIKE. WE HAVE THIS BIPOLAR MOUSE

1359
01:00:27,841 --> 01:00:31,445
FROM MIKE'S GROUP, DSX2 

1360
01:00:31,445 --> 01:00:34,348
KNOCK-OUT AND YOU CAN STILL SEE 

1361
01:00:34,348 --> 01:00:36,984
LOBULES. THE NUMBER DO GO DOWN. 

1362
01:00:36,984 --> 01:00:39,953
IN FACT, IF YOU MEASURED THE 

1363
01:00:39,953 --> 01:00:41,755
NUMBER OF SYNAPSES THESE LOBULES

1364
01:00:41,755 --> 01:00:49,029
MAKE WE HAVE NOW OF COURSE 

1365
01:00:49,029 --> 01:00:50,964
BIPOLAR CELLS DOESN'T INCREASE 

1366
01:00:50,964 --> 01:00:56,536
WHICH MEANS A2AMOCYN CELL LIKES 

1367
01:00:56,536 --> 01:00:59,272
BIPOLAR AS PRIMARY SYNAPTIC 

1368
01:00:59,272 --> 01:01:01,141
PARTNER, TAKE AWAY, I WILL JUST 

1369
01:01:01,141 --> 01:01:04,077
DO GANGLION CELL BECAUSE THE 

1370
01:01:04,077 --> 01:01:06,179
ROLE FOR EXAMPLE THE BIPOLAR IN 

1371
01:01:06,179 --> 01:01:09,383
THE GANGLION CELL MUST BE VERY 

1372
01:01:09,383 --> 01:01:11,785
DIFFERENT. ALSO COULD BE THE 

1373
01:01:11,785 --> 01:01:13,520
HIERARCHY OF CHOICES IS WITHIN A

1374
01:01:13,520 --> 01:01:16,923
CLASS OF CELLS. YOU KNOW WE GOT 

1375
01:01:16,923 --> 01:01:19,092
RID OF ROD AND OTHER BIPOLARS 

1376
01:01:19,092 --> 01:01:21,928
AND PICKED THE OFF-CONE BIPOLAR 

1377
01:01:21,928 --> 01:01:25,499
BUT A17 DIDN'T GO CRAZY AND 

1378
01:01:25,499 --> 01:01:29,669
SYNAPSE OTHER AMOCYN AND GANG 

1379
01:01:29,669 --> 01:01:31,972
CELL S SO MIGHT BE WITHIN THE 

1380
01:01:31,972 --> 01:01:33,273
PREOR POST SYNAPTIC CLASS THAT 

1381
01:01:33,273 --> 01:01:43,817
IS THE PRIMARY CHOICE. I THINK I

1382
01:01:45,385 --> 01:01:49,623
HAVE A LITTLE MORE TIME. I 

1383
01:01:49,623 --> 01:01:51,625
WANTED TO PICK SOME TOPICS I 

1384
01:01:51,625 --> 01:01:54,161
FELT MY COLLEAGUES HERE MIGHT BE

1385
01:01:54,161 --> 01:01:58,031
INTERESTED IN. MANY OF THEM SO 

1386
01:01:58,031 --> 01:02:00,434
MANY THINGS. SOMETHING THAT WILL

1387
01:02:00,434 --> 01:02:01,435
HELP PERHAPS FURTHER THE 

1388
01:02:01,435 --> 01:02:02,903
DISCUSSION BECAUSE MIGHT BE 

1389
01:02:02,903 --> 01:02:03,703
SOMETHING THAT THEY ARE 

1390
01:02:03,703 --> 01:02:05,639
INTERESTED IN. UP TO THIS POINT 

1391
01:02:05,639 --> 01:02:08,408
I HAVE BEEN EMPHASIZING MAKING 

1392
01:02:08,408 --> 01:02:09,576
HANDSHAKING BETWEEN NEURONS IN 

1393
01:02:09,576 --> 01:02:14,381
THE RETINA, MAKING S CIRCUITS 

1394
01:02:14,381 --> 01:02:17,551
BETWEEN NEURONS SO THAT WIRING 

1395
01:02:17,551 --> 01:02:19,586
SPECIFICITY IS IMPORTANT. HOW WE

1396
01:02:19,586 --> 01:02:22,255
THINK ABOUT GLIAL, HAVE NOT 

1397
01:02:22,255 --> 01:02:25,025
THOUGHT ABOUT GLIAL CELLS UNTIL 

1398
01:02:25,025 --> 01:02:26,960
RECENTLY BECAUSE WE ARE WATCHING

1399
01:02:26,960 --> 01:02:29,129
IN THE LAB, WORKING WITH DAVID 

1400
01:02:29,129 --> 01:02:38,805
BURRSON. THIS IS NOT DAVID 

1401
01:02:38,805 --> 01:02:41,575
BURRSON. SO I JUST HAVE TO BAKE 

1402
01:02:41,575 --> 01:02:43,643
HIM LOTS OF CAKES. HE IS HAPPY, 

1403
01:02:43,643 --> 01:02:46,746
STARING A THE SCREEN. VERY GOOD 

1404
01:02:46,746 --> 01:02:49,282
MITOCHONDRIA PAINTING, BY THE 

1405
01:02:49,282 --> 01:02:50,684
WAY. SO WHEN SHE'S BEEN LOOKING 

1406
01:02:50,684 --> 01:02:53,186
AT IS ASSOCIATION OF CELLS WITH 

1407
01:02:53,186 --> 01:02:54,855
THE BIPOLAR CELLS. FOR THAT HERE

1408
01:02:54,855 --> 01:03:00,460
IS AN EXAMPLE OF WHAT A MULE 

1409
01:03:00,460 --> 01:03:02,362
CELL LOOKS LIKE OR PROCESSES IN 

1410
01:03:02,362 --> 01:03:07,868
THE RETINA. 3D RECONSTRUCTION, 

1411
01:03:07,868 --> 01:03:10,137
PAINFUL AND FINE PROCESSES, 

1412
01:03:10,137 --> 01:03:13,673
MANUALLY OR ESSENTIALLY WE KNOW 

1413
01:03:13,673 --> 01:03:16,109
THE MULE CELLS ASSOCIATE CLOSELY

1414
01:03:16,109 --> 01:03:24,417
WITH MEMBRANE OF MANY NEURON, 

1415
01:03:24,417 --> 01:03:25,051
ESPECI

1416
01:03:25,051 --> 01:03:26,286
AXONS OF BIPOLAR AND WHERE THE 

1417
01:03:26,286 --> 01:03:28,588
RIBBON IS. SHE ASKED ARE THESE 

1418
01:03:28,588 --> 01:03:30,690
PROCESSES -- DO THEY JUST COME 

1419
01:03:30,690 --> 01:03:33,160
UP RANDOMLY AND FILL UP SPACE? 

1420
01:03:33,160 --> 01:03:38,331
WE KNOW WHAT MULE CELLS DO 

1421
01:03:38,331 --> 01:03:41,801
FUNCTION FOR PRODUCTION OF 

1422
01:03:41,801 --> 01:03:43,670
GLUTAMATE AND FUNCTIONS. GO SEE 

1423
01:03:43,670 --> 01:03:46,139
OTHER REASONS AND OTHER ROWS, 

1424
01:03:46,139 --> 01:03:47,874
FORMULA CELLS IN TERMS OF WHAT 

1425
01:03:47,874 --> 01:03:50,076
THEY DO IN THE RETINA. WE WANTED

1426
01:03:50,076 --> 01:03:52,179
TO KNOW HOW THEY ASSOCIATE WITH 

1427
01:03:52,179 --> 01:03:57,417
THE BIPOLARS. SO HERE ARE THE 

1428
01:03:57,417 --> 01:04:00,420
MUELLER CELLS IN MAGENTA. SO 

1429
01:04:00,420 --> 01:04:02,989
CONNECTIONS NEXT TO THE AXON 

1430
01:04:02,989 --> 01:04:09,396
TYPES O F BIPOLAR CHEELLS, THISS

1431
01:04:09,396 --> 01:04:12,032
ONE ACROSS MANY. YOU CAN SEE THE

1432
01:04:12,032 --> 01:04:13,900
TYPE FIVE BIPOLAR CELL IS 

1433
01:04:13,900 --> 01:04:16,803
PAINTED, ITS AXON AND PROCESSES 

1434
01:04:16,803 --> 01:04:20,173
ARE PAINTED QUITE STRONGLY WITH 

1435
01:04:20,173 --> 01:04:21,441
MUELLER PROCESSES, WHERE TYPE 

1436
01:04:21,441 --> 01:04:24,778
SIX IS VERY LITTLE ASSOCIATION 

1437
01:04:24,778 --> 01:04:27,547
HERE. SHE'S BEEN DOING THIS FOR 

1438
01:04:27,547 --> 01:04:29,082
ALL TYPES OF BIPOLAR CELLS AGAIN

1439
01:04:29,082 --> 01:04:31,851
IN THE MASS, ROD BIPOLAR CELLS 

1440
01:04:31,851 --> 01:04:34,955
ARE HEAVY PAINTED TYPE 5s 

1441
01:04:34,955 --> 01:04:36,623
BIPOLAR CELLS WHICH ARE STILL 

1442
01:04:36,623 --> 01:04:41,528
THIS CASE ON, SOME TYPE 3 MAYBE 

1443
01:04:41,528 --> 01:04:44,364
BUT 6 IS NOT MUCH, SORRY, WHERE 

1444
01:04:44,364 --> 01:04:46,099
TYPE 9 DOESN'T HAVE VERY MUCH. 

1445
01:04:46,099 --> 01:04:48,201
IF YOU START QUANTIFYING, AND WE

1446
01:04:48,201 --> 01:04:50,203
WANTED TO START DOING THIS, BUT 

1447
01:04:50,203 --> 01:04:54,207
TYPE 2 HAS VERY LITTLE, TYPE 6 A

1448
01:04:54,207 --> 01:04:57,510
LITTLE, TYPE 5 HAS A LOT MORE BY

1449
01:04:57,510 --> 01:04:58,478
COMPARISON. WHAT COULD THIS 

1450
01:04:58,478 --> 01:05:00,380
DIFFERENCE MEAN? IT COULD MEAN 

1451
01:05:00,380 --> 01:05:04,150
THAT, YOU KNOW, THEY PLAY SOME 

1452
01:05:04,150 --> 01:05:07,621
ROLE IN RESPONSES OF GANGLION 

1453
01:05:07,621 --> 01:05:11,758
CELLS. TYPE 6 PROVIDE MAJOR 

1454
01:05:11,758 --> 01:05:14,294
INPUT ON SUSTAIN OR LIGHT STEP. 

1455
01:05:14,294 --> 01:05:18,565
TYPE 5s I AND OTHERS PROVIDE 

1456
01:05:18,565 --> 01:05:24,804
MAJOR INPUT TO GANGLION CELLS 

1457
01:05:24,804 --> 01:05:27,540
AND SPIKE. IF YOU RECALL FROM 

1458
01:05:27,540 --> 01:05:29,309
GANGLION CELLS THEY LOOK SIMILAR

1459
01:05:29,309 --> 01:05:31,244
IN THEIR RESPONSES, CURRENTLY 

1460
01:05:31,244 --> 01:05:32,812
RESPONSES AND THE GANGLION 

1461
01:05:32,812 --> 01:05:34,547
CELLS, HERE IS SUSTAINED AND 

1462
01:05:34,547 --> 01:05:36,049
HERE IS THE TRANSIENT. I DON'T 

1463
01:05:36,049 --> 01:05:37,717
KNOW IF THERE IS ANYTHING TO DO 

1464
01:05:37,717 --> 01:05:41,821
WITH THIS, JEFF. YOU CAN TALK 

1465
01:05:41,821 --> 01:05:44,424
AGAIN BECAUSE THIS EXPERIMENTS 

1466
01:05:44,424 --> 01:05:52,799
OF GALTOM. THE, EXPRESS IN THESE

1467
01:05:52,799 --> 01:05:56,603
CELLS TO GET A READOUT OF 

1468
01:05:56,603 --> 01:05:58,271
GLUTAMATE IN TISSUE BUT THE 

1469
01:05:58,271 --> 01:06:01,374
EXPRESS IS ON DENDRITE OF CELL 

1470
01:06:01,374 --> 01:06:03,343
SO WHATEVER NEAR THE CELLS YOU 

1471
01:06:03,343 --> 01:06:07,314
CAN SEE A FLUORESCENT CHANGE. 

1472
01:06:07,314 --> 01:06:09,983
HERE ARE REGIONS OF INTEREST IN 

1473
01:06:09,983 --> 01:06:11,484
GANGLION CELL FOR EACH REASON 

1474
01:06:11,484 --> 01:06:16,956
AND SEE SUSTAINED GLUTINATE 

1475
01:06:16,956 --> 01:06:19,592
FLORES SENSE IN THE -- DENDRITES

1476
01:06:19,592 --> 01:06:22,862
FOR UNSUSTAINED AND YOU SEE 

1477
01:06:22,862 --> 01:06:24,631
TRANSIENT FLUORESCENT CHANGES. 

1478
01:06:24,631 --> 01:06:26,833
AS JEFF POINTED OUT THESE ARE 

1479
01:06:26,833 --> 01:06:30,770
LONG GLUTAMATE, MILLISECONDS, 

1480
01:06:30,770 --> 01:06:34,607
NOT JUST SECONDS, BUT WHY DO WE 

1481
01:06:34,607 --> 01:06:41,047
SEE THIS. DUE TO ASSOCIATION HOW

1482
01:06:41,047 --> 01:06:44,784
MUCH MUELLER CELLS ARE NEAR 

1483
01:06:44,784 --> 01:06:46,953
AXONS OR SYNAPTIC SITES. ONE OF 

1484
01:06:46,953 --> 01:06:50,790
THE FUNCTION IS SOAK UP 

1485
01:06:50,790 --> 01:06:52,559
GLUTIMATE THROUGH THEIR 

1486
01:06:52,559 --> 01:06:54,394
TRANSPORTERS. WE ARE NOT THERE 

1487
01:06:54,394 --> 01:06:56,796
YET BUT INTERESTING OBSERVATION 

1488
01:06:56,796 --> 01:06:59,599
THAT EVEN GLIA IN RETINA HAS 

1489
01:06:59,599 --> 01:07:04,170
SOME SPECIFICITY IN PART NERSHI 

1490
01:07:04,170 --> 01:07:06,339
WE WANT TO MAKE. TEN MINUTES, 

1491
01:07:06,339 --> 01:07:07,674
THEN WE CAN ALL GO. FINALLY 

1492
01:07:07,674 --> 01:07:11,578
WHERE ARE WE NOW? WE TRYING TO 

1493
01:07:11,578 --> 01:07:14,948
I.N.S. CIRCUITRY IN DISEASE AND 

1494
01:07:14,948 --> 01:07:16,282
HOW WE THINK ABOUT THAT OF 

1495
01:07:16,282 --> 01:07:17,884
THINKING ABOUT THE CIRCUITS, 

1496
01:07:17,884 --> 01:07:20,353
WHAT HAPPENS IN TERMS OF REPAIR.

1497
01:07:20,353 --> 01:07:21,988
WE KNOW THIS BEAUTIFUL 

1498
01:07:21,988 --> 01:07:23,356
ORGANIZATION CAN BE COMPLETELY 

1499
01:07:23,356 --> 01:07:25,325
DISRUPTED BY MANY DISEASES. THIS

1500
01:07:25,325 --> 01:07:31,398
JUST ONE EXAMPLE, RETINITIS 

1501
01:07:31,398 --> 01:07:35,268
WHERE RODS REACH TO INNER RETINA

1502
01:07:35,268 --> 01:07:38,938
TO GANGLIAL CELL. WE DON'T HAVE 

1503
01:07:38,938 --> 01:07:40,640
A DISEASE MODEL BUT FIGURED IT 

1504
01:07:40,640 --> 01:07:44,778
WOULD BE INTERESTED TO LOOK AT 

1505
01:07:44,778 --> 01:07:46,279
THE FULL WHICH HASN'T BEEN 

1506
01:07:46,279 --> 01:07:48,348
LOOKED AT IN FULL DETAIL WHEN 

1507
01:07:48,348 --> 01:07:51,518
COMES TO CIRCUITRY OR IN SOME 

1508
01:07:51,518 --> 01:07:53,953
DISEASE. IS CIRCUITRY ITSELF. WE

1509
01:07:53,953 --> 01:07:56,756
KNOW THERE'S SPECIALIZED 

1510
01:07:56,756 --> 01:07:57,857
ORGANIZATION IN THE PRIMATE 

1511
01:07:57,857 --> 01:08:01,428
PHOBIA INCLUDING OUR OWN WHERE 

1512
01:08:01,428 --> 01:08:02,996
MIDGET PATHWAY SINGLE CONE 

1513
01:08:02,996 --> 01:08:07,200
CONNECTS THROUGH A PAIR OF ON 

1514
01:08:07,200 --> 01:08:10,170
AND OFF BIPOLAR CELL THAT 

1515
01:08:10,170 --> 01:08:13,706
CONNECTS TO GANGLION CELLS, LIKE

1516
01:08:13,706 --> 01:08:15,208
PRIVATE LINE. THERE IS A LOT 

1517
01:08:15,208 --> 01:08:17,510
MORE CONVERGENCE AND DIVERSE 

1518
01:08:17,510 --> 01:08:20,213
AGAINST. THERE IS PRIVATE LINE 

1519
01:08:20,213 --> 01:08:23,750
ALSO EXISTS IN THIS PHOBIA. 

1520
01:08:23,750 --> 01:08:25,718
TYRO, AN OPHTHALMOLOGIST, BACK 

1521
01:08:25,718 --> 01:08:27,520
IN JAPAN NOW, CAME OVER AND HAD 

1522
01:08:27,520 --> 01:08:31,157
BROUGHT SOME EYES THAT HAD 

1523
01:08:31,157 --> 01:08:33,993
RECEIVED LASER TREATMENT. THAT 

1524
01:08:33,993 --> 01:08:37,897
SHOULD BE A CELL HERE. THIS WAS 

1525
01:08:37,897 --> 01:08:41,468
IN BASICALLY WHERE THEY WERE 

1526
01:08:41,468 --> 01:08:44,604
BURNING OFF AUTO RECEPTORS USING

1527
01:08:44,604 --> 01:08:48,174
A LASER CALLED AGULATION METHOD 

1528
01:08:48,174 --> 01:08:51,845
TO SEE NEW PHOTO RECEPTORS AND 

1529
01:08:51,845 --> 01:08:53,780
LOOK FOR REPAIR. THEY ARE DEPEND

1530
01:08:53,780 --> 01:09:00,153
RATING A  -- THEY ARE GENERATING

1531
01:09:00,153 --> 01:09:02,856
A MODEL. SO THE ANIMALS, TISSUE,

1532
01:09:02,856 --> 01:09:06,860
EYES SENT TO US. BASICALLY MANY 

1533
01:09:06,860 --> 01:09:08,628
REGIONS BUT THE LASER TREATMENT 

1534
01:09:08,628 --> 01:09:12,398
STARTED EITHER AT TWO WEEKS 

1535
01:09:12,398 --> 01:09:21,274
BEFORE FIXIATION OR TWO OR SIX. 

1536
01:09:21,274 --> 01:09:22,342
WE COULD SEE THE CHANGE OVER 

1537
01:09:22,342 --> 01:09:24,878
TIME. THIS IS AN EMA OF THIS 

1538
01:09:24,878 --> 01:09:27,714
REGION THAT'S BEEN LASERED, SO 

1539
01:09:27,714 --> 01:09:31,851
AROUND HERE. YOU CAN SEE ALL THE

1540
01:09:31,851 --> 01:09:35,555
FIBER HERE, MORE SPACE WITH 

1541
01:09:35,555 --> 01:09:39,526
CONES ANYMORE. RPE IS STILL 

1542
01:09:39,526 --> 01:09:41,027
INTACT. THESE ARE EDGE, FLOPPED 

1543
01:09:41,027 --> 01:09:43,263
OVER A LITTLE BIT BUT ALL HAVE 

1544
01:09:43,263 --> 01:09:45,398
ALL THEIR SEGMENTS. THIS 

1545
01:09:45,398 --> 01:09:46,499
SCHEMATIC REALLY BROUGHT HOME TO

1546
01:09:46,499 --> 01:09:48,434
ME HOW DIFFERENT THE PHOBIA IS 

1547
01:09:48,434 --> 01:09:53,540
IN TERMS FOR US TO THINK ABOUT 

1548
01:09:53,540 --> 01:09:55,475
REPAIR. HERE WE LASERED AND 

1549
01:09:55,475 --> 01:09:57,243
KILLED OFF BUT CONNECTIONS OF 

1550
01:09:57,243 --> 01:09:59,779
PHOTO RECEPTORS WERE HERE 

1551
01:09:59,779 --> 01:10:02,348
BECAUSE OF FIBER EXTEND HUNDREDS

1552
01:10:02,348 --> 01:10:05,818
OF MICRONS AND MAKE CONNECTIONS 

1553
01:10:05,818 --> 01:10:07,453
WITH THE BIPOLARS HERE, OKAY. IF

1554
01:10:07,453 --> 01:10:08,888
YOU WERE TO TAKE THIS RE-JOHN 

1555
01:10:08,888 --> 01:10:13,993
FOR EM, YOU WILL SEE THERE ARE 

1556
01:10:13,993 --> 01:10:15,361
NO COMPARABLES BUT THE CONE CELL

1557
01:10:15,361 --> 01:10:19,065
BODIES WERE UP HERE. WHAT WE 

1558
01:10:19,065 --> 01:10:21,734
FOUND IS FAR FROM THIS DEPRIVED 

1559
01:10:21,734 --> 01:10:23,670
ZONE WHERE ALL THE CELLS HAVE 

1560
01:10:23,670 --> 01:10:26,072
DISAPPEARED. SO IN THIS AREA YOU

1561
01:10:26,072 --> 01:10:28,441
SEE THE MIDGET CONNECTIVITY BOTH

1562
01:10:28,441 --> 01:10:38,985
ON AND OFF PRIVATE LINE. IN THE 

1563
01:10:41,654 --> 01:10:43,756
PARTICLE MAKE HANDSHAKE AND SIX 

1564
01:10:43,756 --> 01:10:45,291
MONTHS POST ABLATION SUGGESTING 

1565
01:10:45,291 --> 01:10:48,394
YOU HAVE THIS ON-AND-OFF 

1566
01:10:48,394 --> 01:10:49,762
ORGANIZATION. IN THIS BOUNDARY 

1567
01:10:49,762 --> 01:10:52,832
YOU SEE WEIRD THINGS SOMETIMES. 

1568
01:10:52,832 --> 01:10:55,602
YOU CAN SEE DIVERGENCE AND 

1569
01:10:55,602 --> 01:10:56,669
CONVERGENCE IN MIDGET PATHWAY 

1570
01:10:56,669 --> 01:10:58,771
THAT IS NOT NORMAL. I WON'T HAVE

1571
01:10:58,771 --> 01:11:03,543
TIME TO TALK ABOUT THE SCHETOM 

1572
01:11:03,543 --> 01:11:05,144
BOUNDARY, WHICH YOU MAY BE 

1573
01:11:05,144 --> 01:11:06,646
INTERESTED BUT WANT TO TALK 

1574
01:11:06,646 --> 01:11:09,616
ABOUT DISCONNECTED MIDGET CELLS.

1575
01:11:09,616 --> 01:11:11,017
WHAT HAPPENS TO THEM? WHEN THERE

1576
01:11:11,017 --> 01:11:12,852
ARE NO MORE CONES FROM -- THIS 

1577
01:11:12,852 --> 01:11:14,921
IS SIX MONTHS. IN GENERAL IT IS 

1578
01:11:14,921 --> 01:11:17,390
HARD TO TELL WHETHER THERE IS A 

1579
01:11:17,390 --> 01:11:19,626
CHANGE IN CONVERGENCE OR 

1580
01:11:19,626 --> 01:11:21,794
DIVERGENCE AT ALL. THIS CASE 

1581
01:11:21,794 --> 01:11:22,795
CONVERGENCE. SOMETIMES EVEN IN 

1582
01:11:22,795 --> 01:11:25,531
THE NORMAL PHOBIA YOU MIGHT NOT 

1583
01:11:25,531 --> 01:11:27,967
SEE A ONE-TO-ONE. THERE ARE 

1584
01:11:27,967 --> 01:11:31,671
SOMETIMES TWO CELLS THAT ARE 

1585
01:11:31,671 --> 01:11:33,606
CONNECTED. BUT WHAT CLEAR IS 

1586
01:11:33,606 --> 01:11:37,310
NUMBER OF SYNAPSES IN THE OFF IN

1587
01:11:37,310 --> 01:11:40,680
THIS PARTICULAR CASE DEFINITELY 

1588
01:11:40,680 --> 01:11:44,183
GOES DOWN, OKAY. THESE WILL BE 

1589
01:11:44,183 --> 01:11:48,388
SYNAPSES HERE. THE SAME 

1590
01:11:48,388 --> 01:11:52,191
DIVERGENCE, BY HOW MANY BIPOLAR 

1591
01:11:52,191 --> 01:11:55,361
CELLS IS ONE-TO-ONE BUT WE NEED 

1592
01:11:55,361 --> 01:11:58,631
30 CELLS TO BE CERTAIN. NOT 

1593
01:11:58,631 --> 01:12:02,702
GOING TO MAKE TOO MUCH OF THE 

1594
01:12:02,702 --> 01:12:05,171
DIVERGENCE OR CONVERGENCE BUT 

1595
01:12:05,171 --> 01:12:06,339
DECREASED SYNAPSES IN THE OFF 

1596
01:12:06,339 --> 01:12:09,075
CELLS. WHEN WE LOOKED A LOT MORE

1597
01:12:09,075 --> 01:12:12,111
-- THINK WILL SHOW HERE -- 

1598
01:12:12,111 --> 01:12:13,479
EVENTUALLY WE ALSO FOUND IF YOU 

1599
01:12:13,479 --> 01:12:16,182
LOOK AT RIBBONS INSTEAD, SO ALL 

1600
01:12:16,182 --> 01:12:19,485
SYNAPSES. YOU LOOK AT ON-AND-OFF

1601
01:12:19,485 --> 01:12:22,088
CELLS BASICALLY THE AMOUNT OF 

1602
01:12:22,088 --> 01:12:24,257
AXONAL MATERIAL, TERMINAL 

1603
01:12:24,257 --> 01:12:25,858
LENGTH, DOESN'T CHANGE ALL THAT 

1604
01:12:25,858 --> 01:12:29,529
MUCH. BUT YOU SEE THIS DROP IN 

1605
01:12:29,529 --> 01:12:31,531
SYNAPSES. THIS CASE REALLY BOTH 

1606
01:12:31,531 --> 01:12:34,667
ARE ON AND FOR OFF. THE DECREASE

1607
01:12:34,667 --> 01:12:38,104
IN OUTPUT SYNAPSE, RIBBONS IN 

1608
01:12:38,104 --> 01:12:40,073
THIS STAGE, OCCURS BETWEEN TWO 

1609
01:12:40,073 --> 01:12:42,408
WEEKS AND TWO MONTHS 

1610
01:12:42,408 --> 01:12:43,309
POST-ABLATION SO THIS 

1611
01:12:43,309 --> 01:12:45,211
PROGRESSIVE LOSS OF CONNECTIONS 

1612
01:12:45,211 --> 01:12:47,680
OR SYNAPTIC SITES BETWEEN CELLS 

1613
01:12:47,680 --> 01:12:49,315
THAT MAKE THE HANDSHAKE. MOST OF

1614
01:12:49,315 --> 01:12:53,886
THE TIME IT IS A SINGLE MIDGET 

1615
01:12:53,886 --> 01:12:55,688
BIPOLAR TO GANGLION CELL. SO IT 

1616
01:12:55,688 --> 01:12:57,757
IS STILL KIND OF MARRIED TO THE 

1617
01:12:57,757 --> 01:12:59,459
SAME WHATEVER, IT IS JUST 

1618
01:12:59,459 --> 01:13:01,294
TALKING LESS. FEWER SITES OF 

1619
01:13:01,294 --> 01:13:03,096
COMMUNICATION BECAUSE OF LOSS OF

1620
01:13:03,096 --> 01:13:06,632
SOME RIBBONS. WHATEVER REMAINS, 

1621
01:13:06,632 --> 01:13:08,868
THOSE SYNAPSES SEEM TO MAINTAIN 

1622
01:13:08,868 --> 01:13:10,603
NORMAL STRUCTURE ARRANGEMENT. WE

1623
01:13:10,603 --> 01:13:14,907
KNOW MOST OF THE SYNAPSES 

1624
01:13:14,907 --> 01:13:17,710
NORMALLY ARE DIET, WHERE THE 

1625
01:13:17,710 --> 01:13:21,347
WITH BIPOLAR MAKES CONNECTIONS 

1626
01:13:21,347 --> 01:13:25,485
WITH TWO POST SYNAPTIC CELLS AND

1627
01:13:25,485 --> 01:13:27,687
FIND MOST SYNAPSES ARE STILL 

1628
01:13:27,687 --> 01:13:30,156
DIED. SO WHAT IS HAPPENING IS 

1629
01:13:30,156 --> 01:13:33,025
ESSENTIALLY POST-SYNAPSES ARE 

1630
01:13:33,025 --> 01:13:36,562
DROPPING OFF, LOSING RIBBONS AND

1631
01:13:36,562 --> 01:13:38,564
SYNAPSES, LOSING CONNECTION WITH

1632
01:13:38,564 --> 01:13:40,800
GANGLION CELL AND NOT SOMETHING 

1633
01:13:40,800 --> 01:13:42,702
ELSE. NOW SOME THESE 

1634
01:13:42,702 --> 01:13:44,537
REARRANGEMENTS REMIND ME OF THE 

1635
01:13:44,537 --> 01:13:46,005
HUMAN RETINA IN DEVELOPMENT 

1636
01:13:46,005 --> 01:13:48,207
WHERE THERE IS A LOT OF 

1637
01:13:48,207 --> 01:13:50,777
CONVERGENCE AND DIVERGENCE IN 

1638
01:13:50,777 --> 01:13:52,145
RETINA BETWEEN MIDGET BIPOLAR 

1639
01:13:52,145 --> 01:13:55,481
AND GANGLION CELLS. EVENTUALLY 

1640
01:13:55,481 --> 01:13:57,416
THEY ARE ZOOMED AWAY, THOUGH WE 

1641
01:13:57,416 --> 01:13:59,619
DON'T HAVE TIME POINTS EXACTLY 

1642
01:13:59,619 --> 01:14:01,788
WHEN WHEN THESE CONNECTIONS 

1643
01:14:01,788 --> 01:14:02,855
WHICH THE PRIVATE ORGANIZATION 

1644
01:14:02,855 --> 01:14:05,191
WHICH IS DOWN HERE ONE-TO-ONE. 

1645
01:14:05,191 --> 01:14:07,460
YOU CAN SEE BOTH CONVERGENCE AND

1646
01:14:07,460 --> 01:14:08,861
DIVERSE AGAINST, IT TAKES TIME 

1647
01:14:08,861 --> 01:14:10,596
TO SHAPE THAT PRIVATE LINE 

1648
01:14:10,596 --> 01:14:12,665
CONNECTIVITY IN DEVELOPMENT IN 

1649
01:14:12,665 --> 01:14:15,334
HUMAN. BUT WHAT WE THINK IS 

1650
01:14:15,334 --> 01:14:19,071
DIFFERENT IS THAT ALTHOUGH THERE

1651
01:14:19,071 --> 01:14:25,111
ARE CHANGES THIS PALACE TISTY 

1652
01:14:25,111 --> 01:14:26,712
AND DEVELOPMENT BETWEEN THE 

1653
01:14:26,712 --> 01:14:28,014
PATHWAY BETWEEN GANGLION AND 

1654
01:14:28,014 --> 01:14:37,723
BIPOLAR, IN DEVELOPMENT THE 

1655
01:14:37,723 --> 01:14:38,457
REFINE

1656
01:14:38,457 --> 01:14:41,027
REFINEMENT OF THIS NEED TO LET 

1657
01:14:41,027 --> 01:14:43,629
GO. SO IF YOU READ PAPER WITH 

1658
01:14:43,629 --> 01:14:45,364
PRIMARY PARTNER IS ESTABLISHED 

1659
01:14:45,364 --> 01:14:46,999
VERY EARLY AND DOESN'T DECREASE 

1660
01:14:46,999 --> 01:14:51,637
VERY MUCH AT ALL. SO IT SHAPES 

1661
01:14:51,637 --> 01:14:53,406
ITSELF LASTLY BY DROPPING OFF 

1662
01:14:53,406 --> 01:14:56,108
SOME OF THE PARTNERS AND KEEPING

1663
01:14:56,108 --> 01:14:57,176
PARTNERSHIP ONLY WITH ONE 

1664
01:14:57,176 --> 01:14:59,912
GANGLION CELL. IN THE ADULT CONE

1665
01:14:59,912 --> 01:15:02,648
LOSS MODEL, SINGLE PARTNER IS 

1666
01:15:02,648 --> 01:15:04,083
MAINTAINED. DOESN'T REACH OUT TO

1667
01:15:04,083 --> 01:15:06,118
MANY MORE PARTNERS, AS A GENERAL

1668
01:15:06,118 --> 01:15:08,221
RULE. BUT IT IS LOSING SYNAPSES 

1669
01:15:08,221 --> 01:15:13,059
THOUGH IT IS MAINTAINING THE 

1670
01:15:13,059 --> 01:15:13,593
SINGU

1671
01:15:13,593 --> 01:15:19,599
SINGULAR HANDSHAKE. MAKE SENSE, 

1672
01:15:19,599 --> 01:15:21,734
EVERYBODY? GOOD. THERE IS A LOT 

1673
01:15:21,734 --> 01:15:27,340
MORE WORE TO DO WITH THIS AND 

1674
01:15:27,340 --> 01:15:28,608
WHAT THE CHANGES MIGHT BE 

1675
01:15:28,608 --> 01:15:29,775
NEED ED THAT LEAD TO THIS 

1676
01:15:29,775 --> 01:15:34,380
CIRCUIT REMODELLING IN THE 

1677
01:15:34,380 --> 01:15:36,983
MIDGETS, WHAT ARE FUNCTIONAL 

1678
01:15:36,983 --> 01:15:38,718
CHANGES THAT COULD BE REFLECTED 

1679
01:15:38,718 --> 01:15:40,519
IN THE ANATOMICAL CHANGES AND 

1680
01:15:40,519 --> 01:15:44,690
HOW FAST THIS OCCURS. SO YOU 

1681
01:15:44,690 --> 01:15:47,026
HAVE TO DO PHYSIOLOGY. FOR ME 

1682
01:15:47,026 --> 01:15:49,528
THERE IS ALWAYS GOING TO BE SOME

1683
01:15:49,528 --> 01:15:50,796
REMODELLING WE CANNOT RECTIFY. 

1684
01:15:50,796 --> 01:15:53,032
HOW MUCH DO WE NEED TO IN ORDER 

1685
01:15:53,032 --> 01:15:54,901
TO RESTORE VISION AT LEAST TO A 

1686
01:15:54,901 --> 01:15:59,105
LEVEL WE MIGHT BE SATISFIED 

1687
01:15:59,105 --> 01:16:01,374
WITH? MAYBE THE FINEST AND CAN 

1688
01:16:01,374 --> 01:16:04,110
GET THAT ONE-TO-ONE IN FULL 

1689
01:16:04,110 --> 01:16:05,912
GLORY BUT GET CLOSE TO IT AND 

1690
01:16:05,912 --> 01:16:07,413
WHAT WOULD THOSE THINGS BE. I'M 

1691
01:16:07,413 --> 01:16:08,948
GOING TO END WITH THIS SLIDE. I 

1692
01:16:08,948 --> 01:16:10,616
THINK THIS IS GOING TO BE THE 

1693
01:16:10,616 --> 01:16:12,018
SPECIAL CHALLENGE WHEN IT COMES 

1694
01:16:12,018 --> 01:16:14,921
TO THE PHOBIA, OR ANY ANIMALS 

1695
01:16:14,921 --> 01:16:16,956
THAT MEET THE PHOBIA. HOW YOU 

1696
01:16:16,956 --> 01:16:19,258
BRING NEW PHOTO RECEPTORS, 

1697
01:16:19,258 --> 01:16:24,297
WHETHER YOU PUT ORGANITES IN 

1698
01:16:24,297 --> 01:16:26,432
CELLS AND RECEPTORS IN REGION 

1699
01:16:26,432 --> 01:16:27,433
THAT'S LOST AND HAVE THEM 

1700
01:16:27,433 --> 01:16:28,935
CONNECT TO PARTNERS THAT REMAIN 

1701
01:16:28,935 --> 01:16:30,569
THAT ARE NOT IN THE SAME ROOM. 

1702
01:16:30,569 --> 01:16:34,540
THEY ARE KIND OF IN THE NEXT 

1703
01:16:34,540 --> 01:16:36,175
ROOM BUT THEY WERE CONNECTED 

1704
01:16:36,175 --> 01:16:38,277
BEFORE BUT THEY HAVE TO FIND 

1705
01:16:38,277 --> 01:16:42,848
EACH OTHER. YOU WILL SAY WELL 

1706
01:16:42,848 --> 01:16:43,482
DEVELOPMENTAL NEUROBIOLOGIST, 

1707
01:16:43,482 --> 01:16:45,751
GIVE THEM RIGHT FACTORS, HELP 

1708
01:16:45,751 --> 01:16:48,321
THEM GROW PROCESSES AND DO ALL 

1709
01:16:48,321 --> 01:16:50,489
THIS AXON GROWTH PATHWAY STUFF, 

1710
01:16:50,489 --> 01:16:51,857
SHOULD BE ABLE TO GET THEM TO 

1711
01:16:51,857 --> 01:16:55,294
FIND THEIR PARTNERS IN THE NEVER

1712
01:16:55,294 --> 01:16:57,663
ROOM, JUST NEVER GET THEM. 

1713
01:16:57,663 --> 01:17:00,199
SLIGHT PROBLEM. THAT IS THE 

1714
01:17:00,199 --> 01:17:02,802
HUMAN PHOBIA, THE PHOTO -- CONE 

1715
01:17:02,802 --> 01:17:05,771
PHOTO RECEPTORS AND BIPOLAR 

1716
01:17:05,771 --> 01:17:07,406
MIDGETS MAKE THEIR CONNECTIONS 

1717
01:17:07,406 --> 01:17:14,947
VERY EARLY, PRETALNAPRENATALLY,E

1718
01:17:14,947 --> 01:17:19,151
BY MID-GESTATION. PHOTO 

1719
01:17:19,151 --> 01:17:21,320
RECEPTORS LOOK LIKE THIS. THEY 

1720
01:17:21,320 --> 01:17:24,824
DON'T EXTEND THESE FIBER OF 

1721
01:17:24,824 --> 01:17:26,325
HANDS UNTIL THE PIT STARTS TO 

1722
01:17:26,325 --> 01:17:27,593
FORM. IF THEY DON'T DO IT 

1723
01:17:27,593 --> 01:17:29,061
THROUGH A GROWTH CONE BECAUSE 

1724
01:17:29,061 --> 01:17:30,663
THEY HAVE ALREADY MADE THE 

1725
01:17:30,663 --> 01:17:31,998
CONNECTION WITH THE BIPOLAR 

1726
01:17:31,998 --> 01:17:35,034
CELL. IT IS TONS OF RIBBONS, THE

1727
01:17:35,034 --> 01:17:37,169
SYNAPSES ARE FORMED. SO THE 

1728
01:17:37,169 --> 01:17:42,141
FIBER OF HAND IS PROBABLY 

1729
01:17:42,141 --> 01:17:42,942
EXTENSION TO INTERSTITIAL GROWTH

1730
01:17:42,942 --> 01:17:45,845
SO YOU CAN USE AXON FINDING CUES

1731
01:17:45,845 --> 01:17:47,546
TO GET NEW FULL RECEPTORS TO 

1732
01:17:47,546 --> 01:17:50,683
GROW AXONS TO REACH BIPOLARS IN 

1733
01:17:50,683 --> 01:17:52,618
NEXT ROOM. WE HAVE TO THINK OF 

1734
01:17:52,618 --> 01:17:55,287
OTHER WAYS IF YOU WANT TO REPAIR

1735
01:17:55,287 --> 01:17:57,023
PHOBIA CIRCUITRY TO GET THESE 

1736
01:17:57,023 --> 01:18:00,092
TWO CELL TYPES TOGETHER USING 

1737
01:18:00,092 --> 01:18:01,627
MECHANISMS THAT ARE PROBABLY 

1738
01:18:01,627 --> 01:18:03,295
NOVEL TO THEM, THAT THEY HAVE 

1739
01:18:03,295 --> 01:18:07,266
NOT USED DURING DEVELOPMENT. SO 

1740
01:18:07,266 --> 01:18:09,201
REPAIR DOESN'T OFTEN MEAN 

1741
01:18:09,201 --> 01:18:10,836
REVERSE ENGINEERING AS A 

1742
01:18:10,836 --> 01:18:12,171
DEVELOPMENT. BECAUSE SOME OF THE

1743
01:18:12,171 --> 01:18:16,175
TOOLS USING DEVELOPMENT MAY NOT 

1744
01:18:16,175 --> 01:18:17,676
EVEN BE THERE AND THERE MIGHT 

1745
01:18:17,676 --> 01:18:19,045
NOT EVEN BE STRATEGIES YOU THINK

1746
01:18:19,045 --> 01:18:20,746
YOU JUST HAVE TO, YOU KNOW, TURN

1747
01:18:20,746 --> 01:18:23,382
THE GENE ON AND YOU ARE GOING TO

1748
01:18:23,382 --> 01:18:24,750
DO IT AGAIN BECAUSE IT JUST 

1749
01:18:24,750 --> 01:18:26,318
NEVER USED TO DO IT. I THINK 

1750
01:18:26,318 --> 01:18:28,087
THESE ARE THINGS WE HAVE TO 

1751
01:18:28,087 --> 01:18:29,622
THINK ABOUT WHEN WE HAVE THE 

1752
01:18:29,622 --> 01:18:30,623
CHALLENGE, THE SPECIAL CHALLENGE

1753
01:18:30,623 --> 01:18:32,358
I THINK FOR THE PHOBIA. SO WITH 

1754
01:18:32,358 --> 01:18:35,795
THAT I WANT TO THANK MY LAB, 

1755
01:18:35,795 --> 01:18:37,496
EVERYBODY, MORE OR LESS IN THE 

1756
01:18:37,496 --> 01:18:41,434
LAST 30 YEARS OR SO. SOME YOUNG 

1757
01:18:41,434 --> 01:18:44,070
ONES. YOU CAN SEE WE RECRUIT 

1758
01:18:44,070 --> 01:18:45,204
THEY WILL YOUNG. THE WORK 

1759
01:18:45,204 --> 01:18:49,608
LARGELY OF CHI, NOW AT THE ALLEN

1760
01:18:49,608 --> 01:18:52,011
INSTITUTE. HERE IS CHI. MANY 

1761
01:18:52,011 --> 01:18:55,081
OTHER PEOPLE THAT I HAVE TO 

1762
01:18:55,081 --> 01:18:56,215
THANK AND HAVE NOT TIME TO TALK 

1763
01:18:56,215 --> 01:18:57,583
ABOUT THEIR WORK. MANY 

1764
01:18:57,583 --> 01:18:59,118
COLLEAGUES I HAVE TO THANK ALSO.

1765
01:18:59,118 --> 01:19:04,023
YOU SEE SOME OF THEM HERE. WILL,

1766
01:19:04,023 --> 01:19:05,791
PICTURE NEW ONE, BUT 

1767
01:19:05,791 --> 01:19:07,927
PARTICULARLY WANT TO THANK THE 

1768
01:19:07,927 --> 01:19:09,361
NEI FOR THEIR SUPPORT THROUGH 

1769
01:19:09,361 --> 01:19:13,599
THE 30 YEARS AS AN INVESTIGATOR,

1770
01:19:13,599 --> 01:19:16,168
MY PROGRAM OFFICES WHO HAVE BEEN

1771
01:19:16,168 --> 01:19:17,636
VERY SUPPORTIVE OF OUR LAB 

1772
01:19:17,636 --> 01:19:21,740
PROGRAM. I HIGHLIGHT ANON 

1773
01:19:21,740 --> 01:19:23,075
BECAUSE HE'S ALWAYS SUPPORTED ME

1774
01:19:23,075 --> 01:19:25,678
FROM WHEN I WAS VERY YOUNG TILL 

1775
01:19:25,678 --> 01:19:26,812
NOW. HE'S BEEN A WONDERFUL 

1776
01:19:26,812 --> 01:19:30,015
COLLEAGUE IN TERMS OF DISCUSSING

1777
01:19:30,015 --> 01:19:32,918
SCIENCE, BUT HE'S VERY 

1778
01:19:32,918 --> 01:19:34,687
INSPIRATIONAL BUT ALSO ALWAYS 

1779
01:19:34,687 --> 01:19:35,855
EXTREMELY SUPPORTIVE. EVEN 

1780
01:19:35,855 --> 01:19:37,723
THOUGH I KNOW NOTHING ABOUT 

1781
01:19:37,723 --> 01:19:40,359
GENES AND WE DON'T TALK EXACTLY 

1782
01:19:40,359 --> 01:19:42,495
THE SAME JARGON BUT WE HAVE THIS

1783
01:19:42,495 --> 01:19:43,662
SAME UNDERSTANDING THAT WE ENJOY

1784
01:19:43,662 --> 01:19:45,264
EACH OTHER'S SCIENCE, HOPEFULLY.

1785
01:19:45,264 --> 01:19:46,999
THERE IS MORE TO TALK ABOUT 

1786
01:19:46,999 --> 01:19:50,603
LATER. FINALLY I WANT TO THANK 

1787
01:19:50,603 --> 01:19:57,910
DR. PIATIGORSKY AGAIN AND LONA 

1788
01:19:57,910 --> 01:19:59,311
PIATIGORSKY. I WAS READ ING THIS

1789
01:19:59,311 --> 01:20:01,780
BOOK ON THE PLANE WAS GIVEN TO 

1790
01:20:01,780 --> 01:20:03,282
ME. IT IS WONDERFUL BECAUSE I 

1791
01:20:03,282 --> 01:20:07,119
LOVE ALL SORTS OF ANIMALS. I 

1792
01:20:07,119 --> 01:20:11,357
THINK WHAT I'M LEARNING FROM HIM

1793
01:20:11,357 --> 01:20:12,591
APART FROM GREAT SCIENCE IS 

1794
01:20:12,591 --> 01:20:15,528
MAYBE I SHOULD START LOOKING AT 

1795
01:20:15,528 --> 01:20:15,928
INV

1796
01:20:15,928 --> 01:20:19,532
INVERTEB

1797
01:20:19,532 --> 01:20:20,232
INVERTEBRATES. THERE IS SO MUCH 

1798
01:20:20,232 --> 01:20:21,500
ABOUT THEIR STRATEGIES IN HOW 

1799
01:20:21,500 --> 01:20:28,174
THEY USE THEIR EYES, AND I THINK

1800
01:20:28,174 --> 01:20:32,044
THAT IS USED BY ANY SPECIES TO 

1801
01:20:32,044 --> 01:20:35,814
CREATE AN IMAGE-GATHERING 

1802
01:20:35,814 --> 01:20:37,416
PROCESSING EYE I SUPPOSE THAT IS

1803
01:20:37,416 --> 01:20:41,987
BEST SUITED FOR THAT SPECIES 

1804
01:20:41,987 --> 01:20:43,489
NEEDS. HOPEFULLY I GAVE YOU A 

1805
01:20:43,489 --> 01:20:45,658
FLAVOR OF WHAT WE ARE ABOUT. AND

1806
01:20:45,658 --> 01:20:50,062
I HAVE A LOT TO READ, I REAR. 

1807
01:20:50,062 --> 01:20:52,898
THERE IS A TRILOGY AND MANY OF 

1808
01:20:52,898 --> 01:20:55,634
HIS WORKS. SO THANKS DR. 

1809
01:20:55,634 --> 01:21:00,906
PIATIGORSKY, FOR THIS LECTURE 

1810
01:21:00,906 --> 01:21:03,075
AND THANK THE NIEHS, MICHAEL, 

1811
01:21:03,075 --> 01:21:12,184
FOR THEIR SUPPORT, THANK YOU 

1812
01:21:12,184 --> 01:21:19,291
[ APPLAUSE ]

1813
01:21:19,291 --> 01:21:25,998
    [ OFF MIC ]

1814
01:21:25,998 --> 01:21:26,131
 

1815
01:21:26,131 --> 01:21:36,575
   PU 

1816
01:21:40,813 --> 01:21:42,147
   >> ANAN. 

1817
01:21:42,147 --> 01:21:43,315
   >> THANK YOU FOR THIS 

1818
01:21:43,315 --> 01:21:45,351
WONDERFUL TALK. I DON'T 

1819
01:21:45,351 --> 01:21:47,519
UNDERSTAND ANYTHING ABOUT 

1820
01:21:47,519 --> 01:21:48,387
INVERTEBRATES SO WE WILL TALK 

1821
01:21:48,387 --> 01:21:51,390
ABOUT PHOTO RECEPTORS LATER. I 

1822
01:21:51,390 --> 01:21:53,559
SOMEHOW GOT STUCK WITH RODS AND 

1823
01:21:53,559 --> 01:21:55,894
CONES AND DON'T SEEM TO LEAVE 

1824
01:21:55,894 --> 01:21:59,565
ME. BUT THE QUESTION I HAD IS 

1825
01:21:59,565 --> 01:22:04,603
REALLY MORE FOR YOUR LAST. WHY 

1826
01:22:04,603 --> 01:22:06,538
DID YOU -- WHY IS NOT A GOOD WAY

1827
01:22:06,538 --> 01:22:09,675
TO PUT IT. I WILL SAY IN MOST 

1828
01:22:09,675 --> 01:22:15,281
RETINAL DISEASES, IN HUMANS AT 

1829
01:22:15,281 --> 01:22:18,250
LEAST, PHOBIA CONES REMAIN 

1830
01:22:18,250 --> 01:22:19,485
INTACT. THOUGH THEY ARE NOT 

1831
01:22:19,485 --> 01:22:20,753
FUNCTIONAL THEY ARE THERE. I 

1832
01:22:20,753 --> 01:22:23,188
THINK IT WILL BE FUN TO SEE WHAT

1833
01:22:23,188 --> 01:22:25,924
HAPPENS TO THEIR CONNECTIVITY 

1834
01:22:25,924 --> 01:22:27,960
WITHOUT THE ACTIVITIES, RIGHT? 

1835
01:22:27,960 --> 01:22:29,094
   >> ABSOLUTELY. 

1836
01:22:29,094 --> 01:22:32,231
   >> SAME THING HAPPENS
THAT 

1837
01:22:32,231 --> 01:22:34,233
THE FIRST CELLS -- ACTUALLY ONE 

1838
01:22:34,233 --> 01:22:38,504
OF THE UGLY CELLS THAT DIE IN 

1839
01:22:38,504 --> 01:22:40,506
MACULAR DEGENERATION WILL BE 

1840
01:22:40,506 --> 01:22:40,806
RODS. 

1841
01:22:40,806 --> 01:22:46,178
   >> YES. P  

1842
01:22:46,178 --> 01:22:46,945
   >> RODS I HAVE ALWAYS
FELT 

1843
01:22:46,945 --> 01:22:49,481
ARE THE SOLDIER BEES AND CONES 

1844
01:22:49,481 --> 01:22:52,951
ARE LIKE QUEEN BEES. THERE ARE A

1845
01:22:52,951 --> 01:22:53,252
B

1846
01:22:53,252 --> 01:22:56,121
BUNCH INSIDE AND THE DENSITY, 

1847
01:22:56,121 --> 01:22:58,957
THE RODS IS SORT OF PROTECTING 

1848
01:22:58,957 --> 01:23:01,794
THEM. WHEN THEY BEGIN TO DIE AND

1849
01:23:01,794 --> 01:23:07,499
MACRO DEGENERATION YOU HAVE 

1850
01:23:07,499 --> 01:23:11,337
SCOTOPIC VISION LOSS. SO I'M 

1851
01:23:11,337 --> 01:23:12,938
CURIOUS TO SEE WHEN RODS DIE -- 

1852
01:23:12,938 --> 01:23:14,239
   >> WHAT HAPPENS TO 

1853
01:23:14,239 --> 01:23:15,741
CONNECTIVITY OVER TIME. 

1854
01:23:15,741 --> 01:23:23,449
   >> AND IN THE FOEB 
CORNEAL 

1855
01:23:23,449 --> 01:23:24,983
REGION SO WHEN DYSFUNCTIONAL THE

1856
01:23:24,983 --> 01:23:26,952
STRUCTURE IS THERE, THE 

1857
01:23:26,952 --> 01:23:27,286
CONNECTION. 

1858
01:23:27,286 --> 01:23:29,254
   >> THE SYNAPSE MAY BE 

1859
01:23:29,254 --> 01:23:29,555
DIFFERENT. 

1860
01:23:29,555 --> 01:23:31,357
   >> SO THAT SORT OF -- 

1861
01:23:31,357 --> 01:23:35,194
   >> ALL THAT CAN BE
DONE. I 

1862
01:23:35,194 --> 01:23:37,363
THINK IN THE PAST WHEN YOU WENT 

1863
01:23:37,363 --> 01:23:41,166
TO LOOK AT CONNECTIVITY, THE EM 

1864
01:23:41,166 --> 01:23:43,535
SLIDES IS A REAL PAIN AND NOT 

1865
01:23:43,535 --> 01:23:44,470
CERTAIN WHAT THE FULL 

1866
01:23:44,470 --> 01:23:46,505
RECONSTRUCTION LOOKS LIKE, THE 

1867
01:23:46,505 --> 01:23:50,809
METHODS ALLOW YOU TO DO THAT. IT

1868
01:23:50,809 --> 01:23:53,545
IS VERY PAINFUL INDIVIDUALFUL TO

1869
01:23:53,545 --> 01:23:55,214
PAINT INDIVIDUAL CELLS SECTION 

1870
01:23:55,214 --> 01:23:57,282
BY SECTION THOUGH IT IS ON A 

1871
01:23:57,282 --> 01:24:01,420
TABLET. IF THE AI SYSTEM WORK 

1872
01:24:01,420 --> 01:24:02,821
WITH SCALEABLE MINDS, COMPANY 

1873
01:24:02,821 --> 01:24:04,289
THE ENTIRE EM VOLUME VERY 

1874
01:24:04,289 --> 01:24:06,392
QUICKLY. BECAUSE THEY CAN DO 

1875
01:24:06,392 --> 01:24:08,894
THAT, FOR EXAMPLE IF YOU HAVE 

1876
01:24:08,894 --> 01:24:10,129
GOOD BLOCKS FOR DIFFERENT 

1877
01:24:10,129 --> 01:24:12,197
STAGES, YOU CAN START LOOKING AT

1878
01:24:12,197 --> 01:24:13,499
CONNECTIVITY CHANGES. YOU CAN DO

1879
01:24:13,499 --> 01:24:16,068
THE FUNCTION. YOU HAVE TO DO THE

1880
01:24:16,068 --> 01:24:17,870
PHYSIOLOGY. THEN THE BEST THING 

1881
01:24:17,870 --> 01:24:19,505
WOULD BE CORRELATE PHYSIOLOGY 

1882
01:24:19,505 --> 01:24:27,079
WITH THE MOLECULAR CHANGES WITH 

1883
01:24:27,079 --> 01:24:28,847
WHAT MIGHT BE TRIGGERING 

1884
01:24:28,847 --> 01:24:31,250
SOMETHING, RIGHT. NOT JUST YOU 

1885
01:24:31,250 --> 01:24:34,720
LOSE THIS AND THIS IS THE END 

1886
01:24:34,720 --> 01:24:36,855
POINT. I HAVE TO SAY THAT 

1887
01:24:36,855 --> 01:24:39,191
EVENTUALLY -- SORRY, I HAVE TO 

1888
01:24:39,191 --> 01:24:41,894
SAY THAT THE SCOTOMA BOUNDARY, 

1889
01:24:41,894 --> 01:24:44,029
WHICH I DIDN'T TALK ABOUT, 

1890
01:24:44,029 --> 01:24:46,799
THINGS ARE NOT NORMAL THERE. 

1891
01:24:46,799 --> 01:24:51,103
THAT WAS SURPRISING. WE THOUGHT 

1892
01:24:51,103 --> 01:24:52,771
IS IT BECAUSE OF NEIGHBORS? I 

1893
01:24:52,771 --> 01:24:58,811
DON'T THINK SO. I THINK WHAT WE 

1894
01:24:58,811 --> 01:25:01,780
DID WITH LASER, IT IS A GOOD AS 

1895
01:25:01,780 --> 01:25:04,349
CAN BE BUT NOT A STEP FUNCTION. 

1896
01:25:04,349 --> 01:25:05,851
YOU PROBABLY DIDN'T KILL CELLS 

1897
01:25:05,851 --> 01:25:08,454
AT BOUNDARY BUT PROBABLY MADE 

1898
01:25:08,454 --> 01:25:09,822
THEM SICK, LIKE SUNBURNED OR 

1899
01:25:09,822 --> 01:25:13,091
SOMETHING LIKE THAT. SO WE THINK

1900
01:25:13,091 --> 01:25:15,561
STRUCTURALLY WE HAVE THE OUTER 

1901
01:25:15,561 --> 01:25:18,363
SEGMENTS BUT SOMETHING NEEDS TO 

1902
01:25:18,363 --> 01:25:22,100
RECORD FROM SCLETOMA BOUNDARIES 

1903
01:25:22,100 --> 01:25:24,169
AND HAVE TO SAY IF THIS PART 

1904
01:25:24,169 --> 01:25:26,638
ISN'T FUNCTIONING PROPERLY THIS 

1905
01:25:26,638 --> 01:25:28,507
COULD BE OUTCOME OF THE 

1906
01:25:28,507 --> 01:25:30,375
REWIRING. YOU SEE MOSTLY THE 

1907
01:25:30,375 --> 01:25:35,013
REWIRING IS ACTUALLY AT THE 

1908
01:25:35,013 --> 01:25:39,117
SCLETOMA BOUNDARY. 

1909
01:25:39,117 --> 01:25:40,953
   >> IF I WAS GOING TO DO
THAT 

1910
01:25:40,953 --> 01:25:47,493
I WOULD PUT LASER IN SCONE SIDE 

1911
01:25:47,493 --> 01:25:49,194
MORE THAN THE PHOBIA REGION. 

1912
01:25:49,194 --> 01:25:51,296
   >> YOU COULD DO THAT
TOO. IN 

1913
01:25:51,296 --> 01:25:53,365
FACT, IN THOSE ANIMALS THEY 

1914
01:25:53,365 --> 01:25:56,568
PLACE THOSE LESIONS IN MANY, 

1915
01:25:56,568 --> 01:26:02,307
MANY DIFFERENT REGIONS. HE WAS 

1916
01:26:02,307 --> 01:26:04,309
THE COMPANY FOREVER BUT NOW HE 

1917
01:26:04,309 --> 01:26:07,045
CAN GET TO THOSE QUESTIONS. 

1918
01:26:07,045 --> 01:26:08,614
   >> NOBODY ELSE, I CAN
ASK ONE

1919
01:26:08,614 --> 01:26:09,448
MORE QUESTION. 

1920
01:26:09,448 --> 01:26:10,516
   >> SURE. 

1921
01:26:10,516 --> 01:26:15,621
   >> WHEN DOES REALLY THE
PIT 

1922
01:26:15,621 --> 01:26:16,922
FORMATION BEGIN? 

1923
01:26:16,922 --> 01:26:18,423
   >> IN HUMANS SOMETHING
LIKE 

1924
01:26:18,423 --> 01:26:20,058
25 DAYS FETAL. 

1925
01:26:20,058 --> 01:26:20,993
   >> 25 DAYS FETAL. 

1926
01:26:20,993 --> 01:26:22,528
   >> IT IS PRETTY EARLY.
YOU 

1927
01:26:22,528 --> 01:26:26,131
SEE A LITTLE INDENTATION. IT 

1928
01:26:26,131 --> 01:26:29,801
CARRIES ON UNTIL AFTER BIRTH. 

1929
01:26:29,801 --> 01:26:39,645
   >> BUT AT 25 DAYS NO
OPTIC 

1930
01:26:39,645 --> 01:26:42,514
PIT. WHICH FIRST APPEARS AROUND 

1931
01:26:42,514 --> 01:26:46,351
35 DAYS IN HUMAN FETUS. SO I 

1932
01:26:46,351 --> 01:26:49,755
WOULD THOUGHT FORMATION IS 

1933
01:26:49,755 --> 01:26:58,297
SOMEHOW RELATED. CONES AND 

1934
01:26:58,297 --> 01:27:01,166
GANGLION WHEN TOMMY AND I WERE 

1935
01:27:01,166 --> 01:27:03,869
DOING CLOSER TO 70, 80 DAYS. I'M

1936
01:27:03,869 --> 01:27:06,939
CURIOUS, PIT FORMATION IS TAKING

1937
01:27:06,939 --> 01:27:10,008
PLACE MOST EVEN BEFORE CELL 

1938
01:27:10,008 --> 01:27:10,842
DEFERENCE TAKE PLACE. 

1939
01:27:10,842 --> 01:27:12,744
   >> THE PIT FORMATION --
THE 

1940
01:27:12,744 --> 01:27:15,747
CONES DEVELOP VERY EARLY. SO DO 

1941
01:27:15,747 --> 01:27:18,150
SURPRISINGLY THE BIPOLARS AND 

1942
01:27:18,150 --> 01:27:20,285
GANGLION CELL AND 

1943
01:27:20,285 --> 01:27:22,154
STRATIFICATION. BY MID-GESTATION

1944
01:27:22,154 --> 01:27:24,189
WHERE THERE IS NO PIT, AFTER THE

1945
01:27:24,189 --> 01:27:25,891
PIT STARTS FORMING, THE 

1946
01:27:25,891 --> 01:27:28,327
CONNECTIONS BETWEEN THE CONES 

1947
01:27:28,327 --> 01:27:30,495
AND BIPOLARS ARE ALREADY SET. 

1948
01:27:30,495 --> 01:27:32,564
AND THE GANGLION CELL AND 

1949
01:27:32,564 --> 01:27:34,499
BIPOLAR DEATH THAT OCCURS, THERE

1950
01:27:34,499 --> 01:27:36,535
IS A LOT OF CELL DEATH, IS DONE 

1951
01:27:36,535 --> 01:27:38,136
BY MID-GESTATION. 

1952
01:27:38,136 --> 01:27:43,375
   >> BUT BASED ON WHAT --

1953
01:27:43,375 --> 01:27:48,046
SOLELY AT 80, TEN OR 11 WEEKS. 

1954
01:27:48,046 --> 01:27:50,582
   >> YEAH. SORRY, 25
WEEKS -- 

1955
01:27:50,582 --> 01:27:53,518
DID I SAY DAYS? 

1956
01:27:53,518 --> 01:27:56,655
   >> OKAY. THAT MAKES
SENSE. 

1957
01:27:56,655 --> 01:27:58,023
NOW I'M OKAY. 

1958
01:27:58,023 --> 01:28:03,962
   >> IT IS REALLY FAST,
ANON. 

1959
01:28:03,962 --> 01:28:05,430
   >> ALL RIGHT. 

1960
01:28:05,430 --> 01:28:06,832
   >> I THINK WE ARE READY
FOR 

1961
01:28:06,832 --> 01:28:10,702
THE RECEPTION, THANK YOU ALL. 

1962
01:28:10,702 --> 01:28:12,804
[ APPLAUSE ]

1963
01:28:12,804 --> 01:28:14,072
    

1964
01:28:14,072 --> 01:28:15,641
   >> I WAS JUST ASKED TO
MAKE A

1965
01:28:15,641 --> 01:28:17,476
COUPLE CLOSING REMARKS. I REALLY

1966
01:28:17,476 --> 01:28:22,447
DON'T ALMOST KNOW WHERE TO START

1967
01:28:22,447 --> 01:28:28,687
WITH HAVING HEARD ALL THIS. IN 

1968
01:28:28,687 --> 01:28:31,456
YEARS OF MY CAREER, WORKING IN 

1969
01:28:31,456 --> 01:28:32,324
PORTLAND, OREGON, FOR THOSE OF 

1970
01:28:32,324 --> 01:28:33,992
YOU DON'T KNOW OREGON IS A STATE

1971
01:28:33,992 --> 01:28:36,161
IN THE NORTHWEST ABOUT THREE 

1972
01:28:36,161 --> 01:28:37,396
HOURS FROM SEATTLE. BECAUSE OF 

1973
01:28:37,396 --> 01:28:39,931
THAT I HAVE HEARD RACHEL TALK 

1974
01:28:39,931 --> 01:28:43,135
MANY TIMES OVER THE YEARS. AWARD

1975
01:28:43,135 --> 01:28:45,037
LECTURES, MANY THINGS. ONE THING

1976
01:28:45,037 --> 01:28:47,072
THAT'S TRULY IMPRESSED ME ABOUT 

1977
01:28:47,072 --> 01:28:49,741
RACHEL'S TALKS IS THAT THEY 

1978
01:28:49,741 --> 01:28:51,810
DON'T ALL COME OUT THE SAME. I 

1979
01:28:51,810 --> 01:28:53,412
THINK THAT IS REALLY 

1980
01:28:53,412 --> 01:28:59,551
ILLUSTRATIVE OF THE BREADTH OF 

1981
01:28:59,551 --> 01:29:01,720
AMAZING WORK YOU HAVE DONE. THAT

1982
01:29:01,720 --> 01:29:03,422
CREATIVITY AND BREADTH OF STUFF 

1983
01:29:03,422 --> 01:29:04,756
YOU PRESENTED TODAY. ANOTHER 

1984
01:29:04,756 --> 01:29:06,858
THING THAT REALLY STRUCK ME IS 

1985
01:29:06,858 --> 01:29:10,295
YOU SUMMARIZED SEVERAL DECADES 

1986
01:29:10,295 --> 01:29:12,431
OF WORK HERE OVER SUCH A BREADTH

1987
01:29:12,431 --> 01:29:17,402
OF -- YOU KNOW, YOU TALKED ABOUT

1988
01:29:17,402 --> 01:29:23,008
ANATOMY, IMAGING, PHYSIOLOGY, 

1989
01:29:23,008 --> 01:29:28,046
L 

1990
01:29:28,046 --> 01:29:28,747
RETINAL

1991
01:29:28,747 --> 01:29:38,523
RETINA BY BIOLOGY. THAT IS 

1992
01:29:38,523 --> 01:29:39,524
IMPRESSIVE AND HOW YOU PLACED 

1993
01:29:39,524 --> 01:29:41,927
YOUR WORK IN CONTEXT OF WHAT SO 

1994
01:29:41,927 --> 01:29:43,495
MANY OTHER PEOPLE HAVE DONE IN 

1995
01:29:43,495 --> 01:29:45,363
THAT AREA. BOTH IN YOUR NETWORK 

1996
01:29:45,363 --> 01:29:47,265
AND ALSO A LITTLE BIT OUTSIDE 

1997
01:29:47,265 --> 01:29:49,067
YOUR NETWORK. I THINK THOSE ARE 

1998
01:29:49,067 --> 01:29:52,003
REALLY ALL MODELS OF HOW AMAZING

1999
01:29:52,003 --> 01:29:53,605
SCIENCE REALLY SHOULD BE DONE. 

2000
01:29:53,605 --> 01:29:56,441
SO I WANT TO THANK YOU FOR 

2001
01:29:56,441 --> 01:29:58,577
SHARING YOUR KNOWLEDGE AND 

2002
01:29:58,577 --> 01:30:01,012
EXPERTISE WITH US. BOTH IN THE 

2003
01:30:01,012 --> 01:30:02,714
LAST HOUR AND ALSO JUST OVER, 

2004
01:30:02,714 --> 01:30:05,717
YOU KNOW, THE NEXT 24 HOURS THAT

2005
01:30:05,717 --> 01:30:09,087
YOU'LL BE IN BETHESDA. I WANT TO

2006
01:30:09,087 --> 01:30:10,789
THANK -- THERE IS A GROUP OF 

2007
01:30:10,789 --> 01:30:13,291
PEOPLE WHO REALLY OVER SEES 

2008
01:30:13,291 --> 01:30:18,096
THIS. OBVIOUSLY JORAM, YOU AND 

2009
01:30:18,096 --> 01:30:19,731
LONA, THANK YOU AGAIN. THE GROUP

2010
01:30:19,731 --> 01:30:21,233
THAT DOES THE SELECTION FOR 

2011
01:30:21,233 --> 01:30:24,136
THIS. THERE IS A GROUP, JEREMY, 

2012
01:30:24,136 --> 01:30:27,372
BOB, CAPEL, CONNIE I DON'T 

2013
01:30:27,372 --> 01:30:31,109
BELIEVE IS HERE. I'M NOT GOING 

2014
01:30:31,109 --> 01:30:33,411
TO SAY TOO MANY BECAUSE I DON'T 

2015
01:30:33,411 --> 01:30:35,113
WANT TO LEAVE SOMEBODY OUT. YOU 

2016
01:30:35,113 --> 01:30:38,083
DID A GREAT JOB IN PICKING AND 

2017
01:30:38,083 --> 01:30:41,553
THANKS TO THE FNIH FOR 

2018
01:30:41,553 --> 01:30:45,791
OVERSEEING THIS. WE'VE GOT A 

2019
01:30:45,791 --> 01:30:49,628
RECEPTION. RACHEL, JORAM AND ALL

2020
01:30:49,628 --> 01:30:53,498
STAY SO WE WILL TAKE 

2021
01:30:53,498 --> 01:30:57,836
PHOTOGRAPHS. CAPEL, DON'T RUN 

2022
01:30:57,836 --> 01:30:59,070
OFF ANYWHERE. FOR EVERYBODY 

2023
01:30:59,070 --> 01:31:01,907
ELSE, THERE IS A RECEPTION AND 

2024
01:31:01,907 --> 01:31:05,544
THANK YOU ALL FOR COMING. 

2025
01:31:05,544 --> 01:31:15,754
[ APPLAUSE ]