>> IT'S NICE TO SEE SO MANY
PEOPLE HERE AND WELCOME TO
AUDACIOUS GOALS.
WE STARTED THIS YEARS AGO, IN
ORDER TO GENERATE CAPACITY TO
THE RETINA AND VISION.
WE HAD A BUSY YEAR FOR THE AGI,
WE WANT TO PUT IN A PLUG FOR THE
SPONSOR FOR TODAY.
THE AGI, THIS IS THE SECOND YEAR
OF FUNDING, THE FIRST YEAR IN
2015 WENT TO FIVE COLLABORATIVE
PROJECTS TO DEVELOP IMAGING
TOOLS.
THE CONCEPT OF AGI IS TO RESTORE
FUNCTIONALITY OR IN FACT RESTORE
CELLS IN THE RETINA,
PARTICULARLY THE PHOTORECEPTOR
CELLS AND THE
RETINAL GANGLIAN CELLS
THIS INTO HUMAN PATIENTS.
IN ORDER TO DO THAT WE NEED A
WAY OF LOOKING AT THOSE CELLS TO
IMAGE THOSE CELLS.
SIMILAR TO THE ADVANCES THAT
HAVE BEEN MADE IN RETINAL
DISEASES THROUGH OPTICAL
COHERENCE TOMOGRAPHY, WE NEED
STEPS THAT WILL GET US DOWN TO
THE INDIVIDUAL CELL LEVEL AND
THAT WAS THE FIRST FUNDING
TRENCH OF AGI IN 2015.
THE SECOND FUNDING WHICH
OCCURRED IN AUGUST OF THIS YEAR
2016 IS TWO IDENTIFY BIOLOGIC
FACTORS THAT EFFECT
NEUROREGENERATION IN THE RETINA.
JUST A COUPLE OF POINTS YOU MAY
WANT TO KNOW ABOUT, THERE IS A
VERY INTERESTING ARTICLE IN THE
JOURNAL OF NEUROSCIENCE I THINK
IT WAS OCTOBER 2016, AUTHORED BY
MIKE CRYER AT YALE AND CAROL
MASON ON COLUMBIAOT OUTPUT OF AN
AGI WORKING GROUP, THE TOPIC WAS
TO RECONNECT THE EYE TO THE
BRAIN.
NOT A SIMPLE CONCEPT BUT THESE
TWO PEOPLE HAVE LAID OUT ALONG
WITH THE BACKING OF THE WORKING
GROUP, HAVE LAID OUT SOME REALLY
INTERESTING CONCEPTS, IMPORTANT
THINGS TO KNOW ABOUT IN THIS
VENTURE.
THIS LAST YEAR OR A YEAR AGO AT
THE ARVO MEETING THERE WERE TWO
AGI EVENTS, ONE ON REPLACING
RETINAL GANG LIAISON AN CELLS
AND THE SECTD WAS A TOWN HALL IN
HOW ONE INTERFACES ALL THE
WONDERFUL PRISTINE WONDERFUL
BASIC DISCOVERY BIOLOGY WE HAVE
ANCHORED IN THE RETINA AND HOW
ONE ANCHORS THAT TO HUMAN
DISEASE ULTIMATELY TO HAVE THE
AGI EXTEND TO THE HUMAN DISEASE
CONDITION BUT ONE NEEDS TO HAVE
A SET OF CLINICIANS WHO ARE
RECEPTIVE TO THE IDEAS AND CAN
HELP GIED THE PROCESSES THAT
WILL UNDERPIN THIS SO THAT WE
KNOW WHAT THE TARGETS ARE THAT
WE'RE TRYING TO GET INTO.
BUT ENOUGH ABOUT WHERE WE HAVE
BEEN, I'D NOW LIKE LIKE TO
INTRODUCE ANDIE HUBERMAN, ANDY
IS AN ASSOCIATE PROFESSOR AT
STANFORD, HE'S WITH NEUROBIOLOGY
AND OPHTHALMOLOGY AND ALSO WITH
THE BIO-X PROGRAM WHICH IS AN
INTRIGUING INTERDISCIPLINARY
PROGRAM, ENTREPRENEURIAL PROGRAM
AT STANFORD.
HIS TRAINING, Ph.D. FROM THE
U-CAL DAVIS AND THEN HE DID A
POST DOC WITH BEN BARRIS AT
STANFORD AND IS NOW BACK THERE
AFTER A DETOUR THROUGH UC SAN
DIEGO.
LAST YEAR, HE HAD AN
INCREEING--INTRIGUING PAPER ON
NEURAL ACTIVITY PROMOTES LONG
DISTANCE TARGET SPECIFIC
REGENERATION OF ADULT RETINAL
AXONS.
SO HE IS WORKING IN THE TOPIC OF
HOW TO CONNECT THE RETINAL GANG
LIAISON AN CELLS INTO CENTRAL
PROCESSING WHERE THE SIGNALS CAN
SUBSERVE VISION.
HE HAS HAD OR HAS AGI FUNDING.
HE ALSO HAS A NUMBER OF
SUBSTANTIAL AWARDS IN HIS
BACKGROUND, THE Mc KNIGHT
NEUROSCIENCE AWARD AND THE
COGAN AWARD FOR CONTRIBUTIONS TO
VISION SCIENCE.
ANDY THANK YOU FOR TAKING TIME
TO COME.
WE COOLED OFF THE TEMPERATURES
SPECIAL FOR YOU SO THAT YOU
COULD BE GLAD TO GET BACK TO
STANFORD.
THE TITLE OF ANDY'S TALK IS
VISUAL RESTORATION BRIDGES AND
GAPS TO CURING BLINDNESS IN
HUMAN.
[ APPLAUSE ]
>> FIRST OF ALL, I'M DELIGHTED
TO BE HERE.
I'VE BEEN HERE A COUPLE TIMES
AND EACH TIME I'M STRUCK BY HOW
LARGE THIS PLACE IS AND HOW MUCH
INCREDIBLE SCIENCE IS HAPPENING
AND MEETING WITH THE POST DOCS
AND STUDENTS IS ALWAYS A
HIGHLIGHT AND GRADUATE PROGRAMS
ARE NOT TYPICALLY ASSOCIATED
WITH THIS, BUT AFTER LUNCH WITH
THEM, THE FUTURE IS VERY BRIGHT
AND IT EXCITES ME.
I'VE BEEN WORKING ON VISION
SCIENCE FOR ONE FORM OR ANOTHER
FOR 18 YEARS SO I FELL INTO THIS
GANG LIAISON AN CELL THING
PRETTY YOUNG.
I'M A LIFER, I WILL STAY IN THIS
GAME.
I THINK THERE'S A NUMBER OF
IMPORTANT PROBLEMS THAT BASIC
SCIENTISTS AND CLINICIANS BOTH
NEED TO WORK ON AND I'M VERY
HOPEFUL AND GRATEFUL FOR THE
AGI, NOT JUST BECAUSE WE
RECEIVED FUNDING FOR THEM BUT
WONDERFUL TO HAVE SOME POINT AND
DIRECTION IN WHERE TO APPLY FOR
FUNDS AND SOME OF THE REALLY
CRITICAL--THE FACT THAT PEOPLE
STOOD BACK AND THOUGHT VERY
CAREFULLY ABOUT THE PUBLIC, AND
PEOPLE HERE AT NIH AND NEI AND
THOUGHT CAREFULLY ABOUT WHAT
WERE THE KEY PROBLEMS TO ATTACK,
SO MANY GREAT PROBLEMS TO ATTACK
AND SO I THINK REAL PROGRESS IS
BEING MADE AND I'M DELIGHTED TO
BE PART OF THAT PROGRESS AND
LOOK FORWARD TO MORE.
TODAY, AND I WANT TO THANK THE
DOCTOR FOR THE GENERATION
INTRODUCTION AND TEEF BECKER FOR
BRINGING ME OUT TO TALK ABOUT
OUR WORK SO FAR.
SO TODAY I WILL TALK ABOUT
VISUAL RESTORATION.
I'M NOT AN M. D.
NOT A CLINICIAN BUT I DECIDED
WHOLE HEARTLY A FEW YEARS OKAY
AT SAN DIEGO WORKING IN THE LAB
TO RELATE TO ISSUES RELATED TO
GLAUCOMA AND VISUAL RESTORATION
AND WE TALK ABOUT WHY THAT IS
LATER PERHAPS BUT I ALSO HOPE TO
TALK A BIT ABOUT SOME OF THE
WORK WE ARE DOING ON LINKING
EMOTIONS TO VISION AT THE END IF
THERE'S TIME BECAUSE I KNOW
THERE'S FOLKS FROM THE EYE
INSTITUTE AND THAT'S BOTH
BECAUSE I'M EXCITED ABOUT THAT
WORK BUT BECAUSE I THINK IT
DOVETAILS NICELY WITH THE
TECHNOLOGIES FOR ADDRESSING
BLINDNESS.
SO MY LABORATORY WORKS ON THREE
ASPECTS OF VISION, IT'S A PRETTY
LARGE GROUP OF 15 PEOPLE, A
THIRD WORK ON VISUAL CIRCUIT
ARCHITECT AND YOU ARE ASSEMBLY.
THE GENES AND MOLECULES THAT SET
UP THE VISUAL SYSTEM SO THAT ONE
CAN SEE.
A GOOD PORTION OF MY LAB, MORE
THAN A THIRD IS WORKING ON
VISUAL REPAIR, IN PARTICULAR,
WHY GANG LIAISON AN CELLS
DEGENERATE IN GLAUCOMA, A
PROCESS THAT'S POORLY
UNDERSTOOD, AS WELL AS TRY TO
DEVELOP THERAPEUTICS AND
STRATEGIES FOR THERAPEUTICS TO
RECONNECT THE EYE TO THE BRAIN
WHEN THE GANG LIAISON AN CELLS
ARE INJURED OR DAMAGED BY
GLAUCOMA.
AND THEN A NEW ASPECTS OF MY LAB
THEN THAT I'M EXCITED ABOUT,
I'VE ALWAYS WANTED TO WORK ON
THIS PROBLEM, WHY IS IT, THAT
CERTAIN SENSATIONS ARE MERGED TO
CERTAIN EMOTIONS AND HOW DOES
THAT OCCUR IN THE BRAIN.
IT'S RAPID.
IT'S IMPORTANT.
IT'S A BIG PART OF OUR DAILY
LIFE AND WHEN IT GOES, WHEN
THOSE SYSTEMS GO AWRY, YOU GET
THINGS LIKE PTSD, CHRONIC
ANXIETY AND TRAUMA.
SO IT'S IN THE VISUAL SYSTEM
SENSE, IT'S AN INTERESTING
PROBLEM, SO I HOPE TO GET TO A
BIT OF THAT AT THE END.
SO A LITTLE BIT OF BACKGROUND
THAT SETS UP WHERE WE'RE GOING,
AS MANY OF YOU KNOW, NEURONS IN
THE ADULT MAMMALIAN CNS FAIL TO
REGENERATE AND CELLS IN THE
RETINA, GANG LIAISON AN CELLS
IRCLUEDED ARE LONG PROJECTING
EXCITEATORY NEURONS AND THEY
DON'T REGENERATE AFTER INJURY,
AT LEAST NOT IN MAMMALS, IN COLD
BLOODED VERTEBRATES THEY
REGENERATE AND THAT'S AN
INTERESTING PROBLEM.
BUT AS A RESULT OF THIS CNS
FAILURE, AS IT'S OFTEN CALLED,
NEURODEGENERATIVE DISEASES IN
WHICH SPINAL OR BRAIN ATROPHY OR
INJURY TO THE SPINE OR
CONGENITAL OR DAMAGE INDUCED OR
DISEASE INDUCED CONDITIONS THAT
LEAD TO BLINDNESS, GENERALLY ARE
IRREVERSIBLE AND THE COMMON
TREATMENTS INVOLVENINGS LIKE
WHEELCHAIRS, A LOT OF
OUTSOURCING OF SUPPORT, SEEING
EYE DOGS, CANES AND SO FORTH BUT
THE TECHNOLOGY FOR REPAIRING THE
SYSTEM AND GETTING BLIND PEOPLE
TO SEE AGAIN IS REALLY THE GOAL
AND CURRENTLY THERE ARE NO SUCH
TECHNOLOGIES.
WHY DOESN'T THE CNS REGENERATE?
SO I'M GIVING A LOT OF
INFORMATION IN A BRIEF SLIDE BUT
THERE ARE EXTRINSIC FACTORS,
THAT IS THERE ARE THINGS IN THE
NEURONS, GLIAL SCARS REPELLANT
CUES AND CHEMICAL CUES THAT ACT
AS BARRIERS BOTH PHYSICAL AND
NEUROCHEMICAL TO PREVENT NEURONS
FROM REGENERATING IT'S RATHER
CURSORY BUT FOR THE SAKE OF TIME
IT ILLUSTRATES THE PRINCIPLE.
THERE ARE FACTORS AS THEY AGE,
THEY GROW MUCH MORE SLOWLY THAN
THEY DID DURING DEVELOPMENT,
AXONS, THIS PRINCIPLE WAS
DISCOVERED IN RETINAL CELLS BY
JEFF GOLD BERG WHEN WAS A
GRATDUATE STUDENT IN BEN VALID
AND RELIABLEIS' LAB, THEY GROW
VERY FAST BUT BY THE TIME THEY
REACH ADULTHOOD, THEY DON'T
REGENERATE OR GROW VERY MUCH AT
ALL.
THEY MIGHT EXTEND A COUPLE
MICRONS AND THAT IN ITSELF IS
SOMETHING THAT'S CHANGED
INTRINSICALLY TO THOSE NEURONS
AND THIS ISN'T RELATED TO
REGENERATION BUT OF COURSE AXOT
ME LEADS TO DEATH AND IF THERE'S
NOTHING THERE, THERE'S NOTHING
LEFT TO REGENERATE.
IT'S SOMETHING THAT'S SURPRISING
LITTLE ATTENTION HAS BEEN
FOCUSED ON COMBINING
NEUROPROTECTION WITH THE
STRATEGIES IN THE SAME
EXPERIMENT AND JUST TO
EDITORIALIZE, I THINK THERE'S
SOMETHING THAT WE NEED MORE
EFFORT ON AND THERE ARE PEOPLE
PURSUE THAG AND THAT'S GREAT.
SO THE GOAL OF MY LABORATORY
WITH RESPECT TO THE VISUAL
SYSTEM AND THE AGI ARE TO
DISCOVER STRATEGIES TO TRIGGER
LONG-DISTANCE CNS AXON
REGENERATION.
RECONNECT CNS AXONS, THE OUTPUT
NEURON TO THE HIGH WITH THEIR
TARGETS.
WE WANT TO PROBE THE SPEC
ISOTOPITY OF REGENERATION, IT'S
BEEN A LONG STANDING QUESTION,
IF A RETINAL GANG LIAISON AN
CELL, THESE SO CRITICALLY LINK
IN THE EYE TO PERCEPTION AND
MOTOR FUNCTIONS AS THEY OCCUR IN
THE BRAINING, WHAT WE THINK OF
AS SITE, IF REGENERATION OCCURS
WILL THAT OCCUR SPECIFICALLY OR
WILL THE WRONG--THE NEURONS
CONNECT TO THE WRONG TARGETS,
AND YOU CAN IMAGINE HOW
DETRIMENTAL THAT CAN BE IF THE
SO CALLED DIRECTIVE GANG LIAISON
AN CELLS THAT RESPOND TO UPWARD
MOTION, RECONNECT TO THE SIR
CADIAN CLOCK IN THE BRAIN SO
THAT SOMETHING PLUFS UP IN THE
FIELD THE ANIMAL OR HUMAN BEING
RATHER GETS RESET IN TERMINGS OF
A SIR CADION CLOCK, THATIA A
PROBLEM.
SO MAYBE A REASON WHY THEY DON'T
REGENERATE IS THAT IT'S BET TORE
HAVE NO REGENERATION THAN
INCORRECT REGENERATION AND
THAT'S AN OPEN QUESTION AND I'LL
TALK MORE ABOUT THAT TODAY.
AND THEN THERE'S NOW GROWING
EVIDENCE THAT THERE CAN BE
FUNCTIONAL RESTORATION OF THE
CIRCUITS BUT WE STILL AS A FIELD
UNDERSTAND HOW MUCH REGENERATION
YOU NEED.
HOW MUCH DOES IT TAKE TO
REGENERATE A FUNCTION LIKE
SIGHT?
AND HOW CAN WE INCREASE THOSE
NUMBERS IF THEY NEED TO BE
INCREASED AT ALL?
SO THREEZ ARE CRITICAL ISSUES
THAT CAME UP DURING THE
INTERESTING AND STIMULATING
DISCUSSIONS AND THERE'S SORT OF
A CALL TO REMEMBERRAS IF YOU
WILL AND WE RESPOND TO THE CALL
TO ARMS.
SO, THE INJURED EYE TO BRAIN
PATHWAY IN MOUSE IS WHAT I WILL
BE TALKING ABOUT TODAY.
HERE ARE THE AXONS IN THE OPTIC
NERVE ARE LABELED IN A DARK
COLOR THIS, IS HOW I WILL SHOW
THEM TODAY, THE GANG LIAISON AN
CELLS OF COURSE IN LIVE IN THE
BACK OF THE EYE AND THE NEURAL
RETINA AND THESE ARE EXTREMELY
IMPORTANT NEURONS WITHOUT WHICH
THERE IS NO VISION BECAUSE THE
EYE CAN BE FINE, THE BRAIN CAN
BE FINE BUT IF THOSE WIRES
AREN'T CONNECTED AND CONNECTED
IN THE PROPER WAYS THERE IS NO
VISION.
SO, THE MODEL IS THE OPTIC NERVE
CRUSH MODEL. THIS IS A COMMON
MODEL IN WHICH FORCEPS IS
LOWERED BEHIND THE EYE, THE
RETINA IS CRUSHED AND THOSE
THEY'RE LABELED WITH IA DIE AND
YOU FIEBD UNDER NORMAL
CONDITIONS THERE'S NO
REGENERATION, NO AXONS EXTEND
PASSED LEGION SITE SHOWN BY THE
ASTERISK.
THE QUESTION IS HOW DO WE GET
THESE TO REGENERATE BACK IN THE
BRAIN AND IF IT'S SUCCESSFUL HOW
DO WE STUDY OR DO WE TARGET THE
CORRECT LOCATIONS IN BRAIN.
SO RETINAL GANG LIAISON AN CELLS
DON'T REGENERATE NORMALLY AFTER
OPTIC NERVE LESIONS.
SO A VERY KEY DISCOVERY WAS MADE
BY A LAB AT CHILDREN'S HOSPITAL
HARVARD IN 2008 BY A POST DOC
KEVIN PARK IN HIS OWN LAB IN
MIAMI, IN WHICH THEY SHOWED THAT
A GENE, MTORIS EXPRESSED AT HIGH
LEVELS AND GANGLION CELLS IS
SUPPRESSED BY THE P10 GENE, GOES
DOWN ACROSS DEVELOPMENT AND WHAT
THEY DID WAS KEVIN CREATED A
SITUATION IN THE MOUSE IN WHICH
HE DID A CONDITION OF THE
INHIBITORS, INCREASING MTOR IN
THE EYE, SORT OF MIMICKING THE
LEVELS OF MTORDURING THESE
CELLS, EFFECTIVELY TURNING ADULT
RETINAL GANG LIAISON AN CELLS
INTO THE BABY RETINAL GANG
LIAISON AN CELLS WITH THE
EXPRESSION LEVELS.
HE DID THAT BEFORE HE CRUSHED
THE OPTIC NERVE, THEN HE CRUSHED
THE OPTIC NERVE, AND WHAT SHE
WAS IMPRESSIVE AND I DON'T THINK
ANYONE HAD SEEN THIS MUCH
REGENERATION BEFORE EXCEPT IN
CONDITIONS LIKE CNTF
APPLICATION.
IT WAS STRIKING WHAT WE SAW.
AND WHAT WE'VE REPLICATED MANY
TIMES IT WAS AN IMPORTANT POINT
BECAUSE REGENERATION FIELD OF
SPINAL CORD AND OPTIC NERVES,
SORT OF A NUMBER OF FAILURES TO
REPLICATE OVER THE YEARS AND
IT'S A READILY REPRODUCIBLE
EFFECT.
THE LESION IS HERE AND MANY OF
THOSE THAT STEP DOWN NEAR THE
OPTIC BRAIN OVER HERE, SO THE
PATHWAY TURNS OUT TO BE CRITICAL
AND IT'S KIND OF CONTROVERSIAL
BECAUSE YOU WORRY ABOUT CANCERS
AND THINGS ASSOCIATE WIDE MTOR,
BUT NONE THE LITTLE, THIS
EMERGED THIS MTORMODEL HAS
EMERGED AS THE CRITICAL OR MOST
ROBUST MODEL FOR GENERATING LONG
DISTANCE AXON REGENERATION WITH
A SINGLE TREATMENT.
HOWEVER, P10 DELETION ALONE
INCREASING MTOR WAS INSUFFICIENT
TO PROMOTE THE REGENERATION, THE
AXONS MADE IT ABOUT AS FAR AS
THE DISTAL NERVE AND THIS DID
NOT GROW THROUGH THE KHIHIGH
ASISM THROUGH BRAIN AND THEY
WERE FUNCTIONAL OR VISUAL
RECOVERY IN THESE ANIMALS.
NOW WE SAT BACK AND THOUGHT
ABOUT THIS AND WE DECIDED THAT
AT SOME LEVEL, WE WANTED TO
UNDERSTAND WHETHER OR NOT THE
PRINCIPLES THAT WIRE UP GANG
LIAISON AN CELLS DURING
DEVELOPMENT WOULD APPLY TO
TRYING TO REGENERATE THOSE
GANGLION CELLS IN ADULTHOOD, WE
KNOW DURING DISWEPMENT THAT
THESE ARE ACHIEVED BY GROWING
OUT INTO THE BRAIN AND OOH
DENTIFYING WHICH TARGETS TO
CONNECT TOO IN SPECIFIC WAYS AND
THEY GROW MORE AT THAT AGE AND
LATER VERY, VERY LONG DISTANCES
AND THEY DO THIS IN VERY PRECISE
WAYS.
SO WE STARTED THINKING, MAYBE
THESE PRINCIPLES THAT APPLY
EARLY IN LIFE WOULD APPLY LATER
IN LIFE ONCE GANG LIAISON AN
CELLS ARE REGENERATING, SO WHAT
ALBERT LYNN, THEN A GRADUATE
STUDENT OF MINE DID WHO IS NOW
AT GENENTECH, AND HE PUT GANG
LIAISON AN CELLS INTO A DISH,
GAVE THEM GROWTH FACTORS AND HE
STIMULATED THE CELLS
ELECTRICICALLY AND THE
OTHER--AND OTHER GANG LIAISON AN
CELLS HE DIDN'T STIMULATE.
THIS SCHEMEATIZES WHAT IS SHOWN
IN THE PAPER, AND THIS SHOWS
THAT THE ELECTRICALLY STIMULATED
CELLS WERE GROWN THAT RESEARCH
MUCH LONGER AND LARGER AND THESE
WERE NOT ELECTRICALLY
ACCOUNTAIVE AND THEY USE
PATTERNS OF ACTIVITY TO MIMIC
THE SORTS OF ENDOGENOUS PATTERNS
AND THAT OTHER VS STUDIED AND
DISCOVERED AND STUDIED OVER THE
YEARS AND THAT PROVE IMPORTANT
FOR VARIOUS ASPECTS OF GANG
LIAISON AN CELL WIRING AND
DEVELOPMENT SO ALBERT DECIDED TO
ASK THE STRAIGHT FORWARD
QUESTION, DOES NEURAL ACTIVITY
CONTRIBUTE TO REGENERATION OF
RGC AXONS INVIVO AND THAT'S WHY
MAYBE THEY DON'T GROW VERY FAR,
IF WE WERE TO INCREASE THE LEVEL
OF ACTIVITY, THEY WOULD GROW
FURTHER.
SO SINCE THESE DATA ARE
PUBLISHED, I WILL MOVE THROUGH
THEM QUICKLY AND I WILL HIT THE
IMPORTANT POINTS BUT I WOULD BE
HAPPY TO STOP AT ANY POINT AND
ANSWER QUESTIONS.
AT FIRST HE DIDN'T TAMPER WITH
THE MTOR PATHWAY AT ALL.
HE CRUSHED THE NERVE AND THEN HE
GAVE THE MICE HIGH FREQUENCY AND
STIMIEWLINGSZ, THOU THIS IS A
LOT OF STIMULATION, THIS WAS
ABOUT 10 HOURS A DAY.
SOMETHING A PATIENT WOULD NOT
WANT TO DO AND WE WILL REVISIT
THAT IN A BIT 6789 OTHER GROUPS
PUBLISHED THE FACT THAT,
AND--YOU SEE SIMILAR LEVELS OF
REGENERATION WASN'T VERY FAR AND
NOT VERY MANY ACONS BUT APPLYING
THE ACTIVITY REGIME DID SEEM TO
INCREASE THE AMOUNT OF ACTIVITY
IN THE GANG LIAISON AN CELLS AND
PROMOTE GROWTH IN THE LESION
SITE A LITTLE BIT.
SO HERE'S QUANTIFICATION WITH
THAT, IT WAS SIGNIFICANT AND
NONE OF THEM MADE IT TO THE
KHIHIGHASM WHICH MADE IT FROM
THE CRUSH SITE.
SO NOTHING TO GET TOO EXCITED
ABOUT BUT IT WAS INTRIGUING.
SO WHAT'S THE MECHANISM FOR
THIS, SO WE WONDERED WHETHER
VISUAL STIMULATION COULD PRODUCE
ACTIVITY TO STIMULATE LONG
DISTANCE REGENERATION AND HE
FURTHER TEST THE ROLE OF
ACTIVITY AND REGENERATION OF
GANG LIAISON AN CELLS BY USING
THE DREAD SYSTEM, CHEMICAL
SYSTEM WE CAN TALK ABOUT IN
DETAIL BUT FOR SAKE OF TIME.
YOU INTRODUCE A SYNTHETIC
RECEPTOR, THE KEY NUMBER IS FOUR
OR THE HM3D, THE OTHER ANIMAL
HAS HMFOUR D, PUT IN THE CELLS
WITH THE INJECTION AND WITH THE
APPLICATION OF THE DRUG CNO INTO
ONE SET OF MICE OR THE LITTLER
SET OF MICE, YOU COULD DECREASE
OR INCREASE THE AX MOUNT OF GANG
LIAISON AN CELL SPIKING.
THE NICE THING ABOUT THIS
ALLOWED US TO TEST HOW MUCH WAS
INCREASED OR DECREASED FROM
THESE CELLS AND PATCH
RECORDINGS, HE'S TARGETING ONE
OF THESE CELLS THAT EXPRESSES
ONE OF THESE SYNTHETIC GENES AND
HE SHOW SYSTEM HERE'S NOW THE
HM40 SO IT'S ALL THE SPIKING
SPONTANEOUSLY OR RESPONSE TO
VISUAL STIMULI, SAME EFFECT
SHOWS THAT IF YOU WASH, THE CELL
IS SILENT SO IT'S A GENETIC TTX
EXPERIENCE.
AND THIS AND YOU CAN DO AND
SUPPRESS ACTIVITY THROUGH THE
DURATION OF THIS PERIOD AFTER
THE OPTIC NERVE LESION, THE
OPPOSITE EXPERIMENT--OH, EXCUSE
ME.
WHAT HAPPENS TO REGENERATION?
THIS WAS INTERESTING IT TURNS
AND THERE'S ACTUALLY THAN YOU
WOULD SEE ORD NARRLY, YOU DON'T
EVEN SEE THESE GO UP TO THE
LESION SITE.
MOAF OF THESE DIE WHEN YOU BLOCK
ACTIVITY IN THIS WAY.
SO THAT IS PRESERVING THE LIFE
OF THE GANG LIAISON AN CELLS
AFTER INJURY.
SO HERE, PATCH CLAMP RECORDINGS
FROM THREEZ 3D INFECTED CELLS SO
THAT THE CELLS MERELY SPIKING
ALONG, WASHING CNO, AND NOW
BECAUSE THERE'S SECOND MESSENGER
SYSTEM, LEADS TO OPENING OF
POTASSIUM CHANNEL AND WHAT
HAPPENS IS THE CNO, CAUSES A
DRAMATIC INCREASE ABOUT A
DOUBLING IN THE SPIKE OUTPUT OF
THE GANG LIAISON AN CELL, BOTH
SPONTANEOUS AND EVOKED.
SO WHAT HAPPENS WHEN YOU
REGENERATE IN ACTIVITY IN THIS
MANNER, AND WHAT ALBERT SAW,
I'LL JUST SO YOU SHE'S ARE THE
LOW MAGNIFICATION VIEWS SO YOU
COO SEE, HERE'S THE CHIASM,
HERE'S THE AREA PROXIMAL AND YOU
CAN SEE MANY ARE REGENERATING
THROUGH, DEFINITELY MORE THAN WE
SAW IN TERMS OF USING VISUAL
STIMULATION, THESE GENETIC
APPROACHES ARE INTERESTING, IT'S
ONE VIRAL INJECTION AND THEN
REPEATED INJECTIONS IN THE CNO
OR GUT OR DRINKING WATER.
A FEW AXONS MADE IT TO THE
MIDDLE OF THE OPTIC NERVE, VERY
FEW MADE IT IF ANY, AND THAT'S
DEBRIS, THOSE ARE DEGENERATED
AXONS YOU SEE THERE. SO THE
MORE ACTIVITY, THE MORE LONG
DISTANCE REGENERATION.
IT'S STILL A SMALL NUMBER OF
AXONS BUT NOW WE WERE HOOKED ON
THIS AND WE THOUGHT, WOW, WHAT
WOULD HAPPEN IF WE STARTED
COMBINE THIS WITH OTHER
TREATMENTS THAT TICKLE THE GANG
LIAISON AN CELLS IN TERMS OF
MOLECULAR GROWTH PROGRAMS.
ANOTHER POINT OR TWO ABOUTLET
PROMECHULAR GROWTH PROGRAMS,
THIS IS QUANTIFICATION, THIS IS
THE MOST REGENERATION WE SAW,
SO, THE PATHWAY THAT WE WANT TO
FOCUS ON WAS THIS MTORPATHWAY,
YOU CAN INCREASE MTOR BY
BLOCKING INHIBLETTOR, P10 IN
PREVIOUS SLIDES, AND KEVIN PARK
AND OTHERS HAVE DONE, SO WE
DECIDE TO TAKE A VIRAL STRATEGY
BECAUSE IN TERMS OF TRANSGENIC
HUMANS THAT WILL BE A TOUGH ONE.
ALTHOUGH CRISTP AND INTERESTING
WITH ITS SPECIES SO WE DECIDED
TO TRY TO INJECT AN ADNO VIRUS
INTO THIS AND WE SHOWED THAT THE
IN ADULT RETINA, THIS IS RHEBONE
LEADS TO A ROBUST AMOUNT OF
CELLS AND THE AMOUNT OF
MTORTHAIZ THEY EXPRESS.
HERE'S DOUBLING OF THE AMOUNT OF
CELLS AND THE AMOUNT THAT THEY
EXPRESS.
OKAY, SO NOW, WHAT HAPPENS DOES
THIS DELETION AND I WILL SHOW
YOU WHEN YOU INCREASE RHEB ONE
AND YOU SEE SOMETHING SIMILAR TO
WHAT HAPPEN WHEN IS YOU DECREASE
P10 AND YOU SEE A LOT OF
REGENERATION AND WE KNOW THIS IS
OCCURRING THROUGH ACTIVATION OF
THE MTORPATHWAY BECAUSE THE
EFFECT AND BLOCKED BOO THE
APPLICATION WHICH BLOOKS THE
MTOR PATHWAY.
SO THIS CAN INCREASE
REGENERATION, NOT MUCH,
INCREASING TACKIVITY CAN
INCREASE REGENERATION BUT NOT
MUCH, BUT NONE OF THEM MAKE IT
ALL THE WAY OUT TO THE CHAIASM,
SO ALFRED COMBINED THE DATA FROM
THE TWO.
SO CAN THEY COMBINED PROMOTE
GREATER REGENERATION.
HE LESIONED THE OPERATING
GLOBALLYIC NERVE, INFECTED THAT
EYE AND THE GANG LIAISON AN CELL
WITH RHEBONE AND HE FOUND THAT
THE COMBINED TREATMENT DID LEAD
TO AXONS GROWING DOWN THE OPTIC
NERVE BUT NONE OF THEM MADE IT
TO THE CHIASM, AND WE FIGURED
OUT ABOUT SIX MONTHS TO A YEAR
FIGURING OUT WHAT WAS GOING ON
BECAUSE EVERY ONCE IN A WHILE HE
WOULD SEE AN ANIMAL THAT WOULD
REGENERATE IN THE BRAIN, GIVING
WAY TO THE NEXT PART OF THE TALK
AND WE COULD NOT FIGURE OUT WHAT
WAS GOING ON.
AND I SAID WALK ME THROUGH THE
ENTIRE EXPERIMENT AND WE WERE
DOING VISUAL TESTING ON THE
ANIMALS EVEN THOUGH THEY WE
CAN'T DO VISUAL TESTING AFTER
YOU KILL THE ANIMAL OBVIOUSLY SO
YOU HAVE TO DO BEFORE YOU
SACRIFICE THE ANIMAL TO LOOK AT
NERVE REGENERATION AND SOME OF
THOSE TESTS, ALBERT WAS FORCED
TO CLOSE THE OPPOSITE EYE, FOR
REASONS RELATED TO VISUAL
TESTING I'LL TALK ABOUT A BIT
LATER AND IN THOSE ANIMALS WE
SAW LONG DISTANCE REGENERATION.
I THOUGHT WELL THIS IS REALLY
WEIRD AND SOME OF YOU PROBABLY
ALREADY REALIZE WHY IT'S WEIRD
AND I THINK WE HAVE A HANDLE ON
THIS NOW.
SO ALBERT SET UP THESE
CONDITIONS ALL OF THEM BLIND
CONDITIONS SO HE DOESN'T KNOW
WHAT ANIMALS ARE GETTING
INJENTHED WITH THE RHEB -ONE
VIRUS AND CONTROL VIRUSES SO HE
SAW THAT IF HE LESIONS THESE
NERVES, THE ONES THAT HAVE THE
RHEB ONE TREATMENT, BUT THE
OPPOSITE EYE WAS CLOSED TO BIAS
STIMULATION THROUGH THE OPEN
DAMAGED AND TREATED EYE, WHAT HE
SAW WAS THE AXONS MAKE IT INTO
THE CHIASM, AND ACTUALLY LATER
IN THE BRAIN AS WELL.
SO THE DISTAL ORPTIC NERVE AND
THROUGH THE CHIASM.
AND WE WERE SLIGHTLY DISTURBED
BECAUSE TO OUR KNOWLEDGE THERE
ARE NOT MANY CONNECTIONS IF ANY
BETWEEN THE TWO EYES, AND THAT'S
BEEN REPORTED AND THERE'S
RETINAL-RETINAL CONNECTIONS IN
BIRDS.
THERE MAY BE SOME BUT THEY'RE
NOT VERY MANY IN ANY CASE BUT
THERE'S A SHORT WINDOW IN WHICH
AXONS FROM THE TWO EYES ARE
POSITIONED TO INTERACT WITHIN
THEIR TARGETS AND FACTORS THAT
MIGHT IMPACT THIS, AND THIS IS
SOMETHING FOR DISCUSSION AT THE
END.
SO ALBERT WAS EXCITED BY THIS
AND QUANTIFIED IT ACROSS A
NUMBER OF ANIMALS AND THAT'S
SHOWN HERE IN PURPLE WHICH JUST
TO COLOR CODE TO MAKE IT SIMPLER
WHEN HE CLOSES ONE EYE, DOES THE
VISUAL STIMULATION, AND 10-12
HOURS A DAY, EXCUSE ME AND SEES
A LOT OF REGENERATION ALL THE
WAY TO CHIASM BUT NOT IN OTHER
CONDITIONS.
SO WHEN I CLOSE, OTHER EYE OPEN
HAS TO BE THIS EYE, YOU CAN'T
CLOSE THIS EYE SO HE DID ALL THE
DERIVATIONS, THERE WERE 27
SUPPLEMENTAL FIGURES IN IN PAPER
FOR ALL THE DERIVATIONS, AND
PLUS, INCREASE IN ACTIVITY IN
GANG LIAISON AN CELLS.
NOW IN FIELD OF REGENERATION IS
FILLED WITH RESULTS THAT PEOPLE
AREN'T MOTIVATED OR FUNDED OR
JUST DON'T WANT TO REPORT DOING
AND NOT SEEING THE SAME THING.
I LIKE TO SLEEP WELL AT NIGHT.
I TRUSTED ALBERT AND I STILL
TRUST HIM BUT YOU WANT TO SEE
THIS STUFF VERIFIED
INDEPENDENTLY AND WE ALSO KNOW
THAT THE HM3D APPLICATION LEADS
TO A ROBUST NEURAL ACTIVITY THAN
DOES THE VISUAL SIMULATION AND I
SHOWED YOU THAT EARLIER AND WE
KNOW THAT PRACTICES PRECORDINGS
AND SPIKE OUTPUTS FROM INVIVO
ARE MUCH LESS THAN THESE GENETIC
TOOLS SO I'M DELIGHTED TO SAY,
THAT ALEX'S LAB, DOWN THE ROAD,
FROM THE SCHOOL OF MEDICINE,
ALEX HAS BEEN DOING BEAUTIFUL
WORK, THE MOLECULES THERE AND IS
EAGER TO MOVE INTO THE
REGENERATION FIELD AND APPLY HIS
KNOWLEDGE OF AXON GUIDANCE,
LIGANDS AND MOLECULES HE
DISCOVERED AND CHARACTERIZED TO
THAT SYSTEM.
I WILL TALK MORE ABOUT THIS BUT
ALEX'S GROUP IS NOW
INDEPENDENTLY VERIFIED THIS
RESULT THAT THE COMBINATION OF
HM3D WITH THE INCREASE IN THE
RHEB ONE, LEADS TO REGENERATION,
THE AXONS DOWN THE OPTIC NERVE
AND THIS IS POST CHIASM, THIS IS
WHERE THE IT'S HEADING INTO THE
BREAK AND THE OPTIC TRACKS SO
THAT MAKES ME HAPPY AND
RELIEVED.
YOU KNOW REPPLICATION IS A
TRICKY THING BECAUSE THEN PEOPLE
THINK ABOUT DRVESES IN MOUSE
STRAINS AND HOUSING CONDITIONS
AND THEN THERE'S VISUAL INVOLVED
AND LIGHT-DARK CYCLES SO THERE'S
CERTAINLY MORE WORK TO BE DONE
AND I THINK REPLICATION,
ESPECIALENTIALLY IN THE FIELD OF
REGENERATION WILL BE VERY
IMPORTANT AND AGAIN, I'M
DELIGHTED THAT AGI HAS
HIGHLIGHTED THIS AS ONE OF THE
CRITICAL BULLET POINTS.
REPLICATION OF RESULTS THAT
EVALUATE PROBUSTNESS.
I THINK EVERYONE IN THE FIELD IS
VERY WELL INTENTIONED BUT YOU
KNOW ANY NUMBER OF THINGS CAN
HAPPEN IN TERM OF MOUSE STRAIN
SAYS AND-OF TRAINS AND THIS IS
GREAT.
SO WHERE DO THEY GO?
DO THEY GO TO THE RIGHT PLACE?
WRONG PLACE?
I WILL GIVE YOU THE MESSAGE
QUICKLY.
THIS SAY SCHEMATIC THIS, IS THE
EYE, THE VISUAL TARGETS IN THE
BRAIN AND A NORMAL MOUSE, SOME
OF THEM ARE DEVOIT OF BLACK
LABEL HERE IS THEY SET A MEDIAL
TO THE PANEL OF THE SCREEN BUT
NONETHELESS THERE ARE 40
DIFFERENT TARGETS AND SO YOU
LOVE TO KNOW, DO THE CELLS GO TO
VISUAL TARGETS OR WANDER INTO
THE AUDITORY TARGETS SO WE KNOW
THAT VISUAL NEURONS IN
PARTICULAR, GANG RYAN CELLS ARE
PERFECTLY HAPPY TO GROW INTO THE
THALAMUS IF THEY'RE ALLOWED
WHERE THEY DRIVE THE AUDITORY
PERCEPTIONS.
WE DON'T WANT THAT, RIGHT?
SO THE GOOD NEWS IS THEY STAY IN
THE VISUAL SYSTEM, SO HERE'S A
SAGEITAL VIEW OF MICE THAT
RESEECHED, SCHEMATIC OF THESE
MICE THAT STIMULATE LONG
DISTANCE REGENERATION AND ALBERT
AWE AN AXON OR TWO IN THE SUPER
CHIASMATIC NUCLEUS, HE DIDN'T
DISCOVER IT FIRST, HE SPENT A
LOT OF TIME THERE,
CONGRATULATIONS HE'S HERE.
HE HAS DONE WONDERFUL WORK.
VLGN, ROLE IN EYE MOVEMENTS AND
THE FAMOUS DLG AND THE MOST
FAMOUS SUBCORTICAL TARGET AND IT
RELAYS INFORMATION UP TO VISUAL
CORTEX.
THEY'RE THE PROFILES WERE
LOOKING KIND OF DEGENERATED AND
THESE ARE NOT FABULOUS TERMINALS
BUT WE SAW TERMINALS THERE.
I WILL REVISIT THAT POINT ABOUT
DEGENERATION OF REGENERATED
AXONS IN A BIT.
THE NUCLEUS, WHICH IS INVOLVED
IN PUPIL REFLEXES WE SAW AXONS
THERE.
AND THEN WITH BRAIN STEM--BRAIN
STEM TARGETS THEY'RE INVOLVED
AND YOU MOVE OUR HEAD OR EYES
THE VISUAL WORLD SLIPS ON THE
RETINA BUT UNLIKE A PROORLY
STABILIZED IMAGEOT CELL PHONE,
WHICH IS BLURRY YOU GENERATE A
EYE MOVEMENT AND MOTHER NATURE
SOLVED THAT PROBLEM FOR US AND
IN THE MOST DISTAL TARGET THE
SUPERIOR, WHICH IS INVOLVED IN
DREBLGHTED EYE MOVEMENTS IN THE
LOCATIONS IN THE VISUAL FIELD
AND YOU HAVE MANY PEOPLE HERE
WHO HAVE DONE BEAUTIFUL WORK ON
THAT, INCLUDING BOB WURTZ, OF
COURSE.
THERE'S REGENERATION, I WANT TO
SPEND A BIT OF TIME WITH THIS
SLIDE SO THERE'S IMPORTANT
THINGS, SO THERE'S NO
MISCOMMUNICATION.
FIRST OF ALL, IT'S FEW AXONS
PROBABLY LESS THAN A HUNDRED.
THERE ARE 10,000 GANG LIAISON AN
CELLS IN THE MODEL CITIZEN US
AND HERE WE EVALUATED EVERY
TARGET 10,000 PER EYE AND COULD
BE MANY MORE BUT ABOUT 10,000,
PROBABLY ABOUT A HUNDRED GANG
LIAISON AN CELLS.
THEY SPREAD THESE OUT BROADLY
BUT WITH THE PLASTICITY AND THE
POST SYNAPTIC STRUCTURE RESCUE
FUNCTION.
THE QUANTIFICATION OF THIS, I
HIGHLIGHTED SO YOU DON'T HAVE TO
READ THIS WHOLE TABLE, BUT ZERO
OUT OF 16 OR 13 MICE, NOT
REGENERATE INTO THE TARGET SO
THE MOST ROOF THEERAL OF THE
CHIASM, ARE HERE, AND THIS IS
THE SUPERIOR CO LICKULOUS ARE
HERE.
FIVE OUT OF 10, SIX OOF THE OF
10, SO FORTH, WHAT IS THIS?
THESE ARE ANIMALS THAT HAD ONE
EYE CLOSED, VISUAL STIMULATION
AND THE RHEB-ONE, MTOR,
MTOR,--ACTIVATION, AND SOMETHING
WHERE THE EYE WAS REMOVED, THE
MOST STRONGLY AND REMOVES THE
PHYSICAL SUBSTRATE OF
POSSIBILITY OF OTHER INTACT
AXONS IN THE BRAIN BLOCKING
REGENERATION SO THAT WAS THE
RATIONAL FOR DOING THIS.
YOU NEED THESE THREE THINGS IN
ORDER TO GET LONG DISTANCE
REGENERATION, THE GREAT NEWS IS
THE AXONS STAYED IN THE VISUAL
SYSTEM, NONE OF THEM WANDERED
INTO THE AUDITORY SYSTEM BUT IT
TURNS OUT THAT'S THE CASE SO
SOMETHING IS INHIBITORS IN THOSE
MODALITIES OR SOMETHING IS
KEEPING THISEM IN THE CORRIDOR
OF THE VISUAL SYSTEM, EITHER
STRUCTURAL OR CHEMICAL.
A COUPLE QUICK CONTROLS.
YOU KNOW THIS IS IN THE
MANUSCRIPT BUT WE DID DO
CONTROLS TO MAKE SURE WE WERE
NOT LOOKING AT SPARED AXONS, HOW
DO YOU KNOW IF YOU ACTUALLY
LESION THE AXONS WELL ENOUGH.
IT'S VERY TOUGH.
NOT LIKE OUR STUDIES OF GLAUCOMA
AND DAVID CULKINS AND SAPPING
TONS YOU CAN SEE THE MODEL OF
GLAUCOMA, YOU CAN MEASURE
PRESSURES EVERY DAY AND YOU CAN
KNOW, THIS MOUSE HAD AN INCREASE
OF 30-GRAMS OF MERCURY AND SO
YOU CAN KIND OF GAUGE THE SIZE
OF THE EFFECT, THE MAGNITUDE OF
THE EFFECT AND THE MAGNITUDE OF
THE MEASURE CHANGE AND YOU
CAPTAIN DO THAT IN
REAGAINERATION AND YOU ARE
GUESSING WHAT HAPPENED AFTER THE
EXPERIMENT IS OVER.
SO ALBERT DIDN'T AN EXPERIMENT
WHERE HE PRELABELLED ALL THE
CELLS AFTER IT DIED AND THEN
AFTER THAT HE RELABELED THEM IN
THE SAME EYE WITH THE GREEN DYE
AND NONE OF THE GREEN STUFF IS
ALSO MAGENTA AND NONE OF
THEACONS WERE SPARED
AXONS--EXCUSE ME--NONE OF THEM
WERE SPARED AND YOU SEE THE DIE
BACK OF THE PRELABELLED ONES.
SO THIS CONFIRMED IT THERE
WASN'T SPARING OF AXONS IN THESE
ANIMALS.
HE ALSO DID AN EXPERIMENT WHERE
HE SAID, WELL IF IT'S SPARING OF
AXONS THEN THEY SHOULD BE
VISIBLE IN THE BRAIN AFTER THE
PROTOCOL IS INITIATED BUT IF
THERE'S A KIND OF SUCCESS OF
ACCUMULATION OF GROWING NEURONS,
KIND OF A FLEET OF NEURONS IN
THE BRAIN AND IF YOU SACRIFICE
THEM AFTER ONE WEEK, TWO WEEK OR
THREE WEEKS THEN HE OUGHT TO SEE
LESS MORE AND MORE REGENERATION
AS TIME WENT ON AND THAT'S WHAT
HE SAW.
SO AS TIME WENT ON HE SAW MORE
AND MORE REGENERATION INTO THE
BRAIN.
SO COUPLE WEEKS AFTER VERSES ONE
WEEK AFTER, SO IT'S REALLY A
THREE WEEK SYSTEM WHERE THE
AXONS HIT THE BRAIN AND THAT'S
WHEN THEY GROW REALLY FAST AND
THATY AN ENTREESING THING WE
EVAPORATE FOLLOWED UP BUT I HOPE
SOMEONE DOES, THESE GROW FASTER
IN THE BRAIN THAN THEY DO IN THE
OPTIC NERVE.
NOW THIS IS A QUESTION ABOUT FES
FISCHERITY.
SO ONE THING WE WERE REALLY
INTERESTED IN IS WHETHER OR NOT
THESE GANG LIAISON AN CELLS OF
WHICH THERE ARE ABOUT 30
DIFFERENT TYPES AND I THINK THE
NUMBER IS--I'VE BEEN INVOLVED IN
THIS EXPOSURE TO RADIATION TO
TYPE GANG LIAISON AN CELLS.
I THINK WE ALL AGREE NOW BASED
IN LARGE PART DUE TO THE
BEAUTIFUL YORK OF TIME OILER AND
LITTLERS IN--OTHERS IN THIS
EFFORT, EACH ENCODING A DISTINCT
QUALITY OF INFORMATION AND
SIGNALING IS THAT TO THE BRAIN
AND EACH ONE OF THOSE CELL TYPES
PROJECTING TO A UNIQUE
COMBINATION OF ABOUT FOUR OR
FIVE OF THE POSSIBLE 40
DIFFERENT TARGETS IN THE BRAIN.
SO IT'S A PRETTY COMPLEX PUZZLE.
SO, WE'VE DEVELOPED THESE
DIFFERENT MOUSE LINES OR
CHARACTERIZE DIFFERENT MOUSE
LINES AND EACH IS A SET OF CELLS
THAT CONNECTS TO THE TARGETS IN
THE BRAIN, NORMALLY IS LABEL
WIDE A FLUORESCENT PROTEIN SO I
TRIED TO MAKE THIS AS SIMPLE AS
POSSIBLE, SO ALL THESE RESULTS
ARE PUBLISHED AND THE MICE ARE
FREELYY AVAILABLE THANKS TO THE
GEN-SAT PROJECT.
THESE IS THE CELLS HERE AND HERE
BUT NOT TO THE OTHER TARGETS,
BLUE CELLS PROJECT HERE, HERE,
AND HERE, BUT NOT OTHERS AND SO
FORTH.
SO ALBERT DID THESE EXPERIMENTS
AND ASKED WHETHER OR NOT THE
INDIVIDUAL GANG LIAISON AN CELLS
IF THEY'RE PART OF THE
REGENERATING COHORT WHETHER OR
NOT THEY WIRE UP TO THE CORRECT
TARGETS AND THE RESULTS OF
THOSE--HERE'S ANOTHER MOUSE
LINE.
WE HAVEN'T HIT SATURATION, WE
DON'T HAVE MARKERS FOR ALL 30
BUT COLLECTIVELY AS A FIELD WE
MARKERS FOR 20 WHICH IS PRETTY
EXCITING.
SO AT LEAST FOR THE ALPHA-LIKE
GANG LIAISON AN CELLS, THESE ARE
SIMILAR TO THE PARASOL GANG
LIAISON AN CELLS IN PRIMATE,
THESE AXONS REGENERATE BACK TO
THE KREBLGHT TARGET SO THIS IS
PANELS ALL GANG LIAISON AN CELLS
COLLECTIVELY WITH THE CTB DYE,
AND PSEUDOCOLLORRED HERE IN
BLACK AND THEN THEY'RE MERGED
AND IT SHOWS THAT THESE GREEN
AXONS AND WE SAW THAT THE GREEN
AXONS ARE PRESENT IN THE NORMAL
TARGETS OF THE CELLS SO FOR
INSTANCE THESE CELLS HERE AND
THE DLGN AND OPSC, AND THE
FUNCTIONS OF THESE ARE DIFFERENT
AND THE NAMES, FULL NAMES ARE
NOT IMPORTANT FOR NOW, BUT WHAT
ALBERT SAW IS THAT THE GREEN
AXONS WERE PRESENT WITHIN THOSE
SPECIFIC TARGETS AND THAT MEANS
THAT THESE AXONS ARE GROWING
BACK DOWN THE NERVE THROUGH THE
CHIASM, IN THE BRAIN AND FINDING
AND RECONNECTING TO THE CORRECT
TARGETS.
HORMONE'S ONE AXON, IT'S
EMBEDDED IN AN OCEAN OF AXONS.
WHY ARE SOME GREEN AND NOT
MAGENTA, AND THAT'S BECAUSE
THEY'RE FROM THE OPPOSITE EYE
AND ALBERT INCLUDED DAILY BASIS
THEA AND I INVITE YOU TO LOOK AT
THOSE IF YOU LIKE, IN WHICH HE
THEN INCLUDED OPPOSITE EYE AND
ALL OF THOSE ARE LABELED IN THE
BRAIN AND THOSE HAD TO BE AXONS
THAT WERE REGENERATED AND
LABELED AFTER THE REGENERATION,
SO GANG LIAISON AN CELLS KNOW
WHERE TO GO AND WHERE NOT TO GO
AND I WILL MENTION THAT THERE'S
THREE OR FOUR SUPPLEMENTAL
FIGURES THAT ILLUSTRATE NONE OF
THE TARGETS, I WILL NOT GO
THROUGH THEM FOR SAKE OF TIME.
BUT NONE NONE THE OF THE 40
TARGETS THAT DON'T NORMAL
RECEIVE THOSE F ALPHWACELLS GET
INPUT IN THE REGENRATIVE
CONDITION AND WHEN HE LOOKED AT
THESE PHOTOSENSITIVE AKA MEL
OPERATING GLOBALLYS, THEY
REGENERATE AND THE ONE THATION
REGENERATE GO TO THE RIGHT PLACE
AND NEVER TO THE WRONG PLACE, I
THOUGHT, WELL THIS IS FANTASTIC,
GANG LIAISON AN CELLS KNOW THEIR
WAY HOME, AND THEY'RE
REACTIVATING DEVELOPMENTAL
PROGRAM AND I'LL REVISIT THAT IN
A FEW MINUTES WITH SOME CHEMICAL
OR MOLECULAR DATA AND WE NOW
HAVE A NICE SUITE OF VISUAL
BEHAVIORS MANY OF WHICH TAP INTO
THE TARGETS IN KNOWN WAYS LIKE
THE OPTICAL IMAGES O KINETIC
REFLEX AND THE PUPILARY REFLEX
TO BLUE LIGHT AND CLIFF WHICH IT
RELIES ON CORTEX THROUGH THE
GENICULET, AND IT THE MOUSE
STEPS OFF THE PLATFORM FROM DEEP
TO SHALLOW, BUT I MICE DON'T
KNOW THAT.
AND THE LOOMING RESPONSE IN
RELATION TO THE FEAR WORK IN
WHICH AN OVERHEAD DARK EXPANDING
STISK IS SHOWN, AND THE MOUSE
FREEZES OR FLEES TO SAFETY.
SO HE EVALUATE VISUAL DEHAIEVERS
IN THESE MICE TO SEE IF THE
AXONS REGENERATE BACK INTO THE
BRAIN.
VERY FEW AXONS.
SO HE DID THIS, AND I WILL
SUMMARIZE HERE, PUT SIMPLY, THE
OPTICAL IMAGES O KINETIC REFLEX,
THIS IS A NONLESION ANIMALS
HOOEY DID IT IN THIS A WAY IN
WHICH YOU A NUMBER OF TRIALS THE
MICE TRACK THE VISUAL STIMULUS,
THERE ARE A NUMBER OF WAYS TO DO
THAT BUT THAT'S WHY IT'S 30% OF
TRIALS.
OCCASIONALLY THE MICE DON'T PAY
ATTENTION, THEY DON'T LIKE DOING
PSYCHOPHYSICS EITHER, UNLESS
THEY'RE HAD-FIXED AND THEN THEY
WILL FORCED TOO AND WILL DO IT
MORE OFTEN.
THE LESION WAS EXCITING, IT WAS
ATTRACTED.
THERE WAS NOTHING IN AN LESION
OF AN UNTREATED ANIMAL.
TWHA WAS FSN'T SURPRISING.
IN THE PUPIL REFLEX PALGT WAY,
WE SAW AXONS GRG TO THE TARGETS
OF THE REFLEX BUT WE DIDN'T SEE
ANY RECOVER OF FUNCTION AND THE
AXONS LOOK HEALTH TOW US AND
THIS POINTS TO THE FACT THAT
STRUCTURE AND FUNCTION CAN
SOMEHOW--THEY DEFINITELY RELATE
BUT IT CAN BE MISLEADING WHEN
YOU LOOK AT STRUCTURE.
THE VISUAL CLIP SHOWED NO
RECOVER EXPE THAT WAS DEPRESSING
BECAUSE WE SAW HIM BACK INTO THE
RGC, AND THEY WOULD LIKE THE
SIR CADIAN CLOCK TO THE LIGHT
AND DARK CYCLE, THAT'S IMPORTANT
PHYSIOLOGICAL MANIFESTATION, AND
WHAT WE WANT IS THE
MANIFESTATION OF SITE BUT THEY
WERE BLEVY, AND THEY WERE NOT
HEALTHY OR ABLE TO MEADIAT SIN
APTIC TRANSMISSION OR POST SIN
APTIC CELLS.
SO VISION ISN'T COMPLETELY
RESTORED BUT THERE'S PAICIAL
RECOVERY OF FUNCTION IN THESE
TWO BEHAVIORS, THE OPTICAL
IMAGES O KINETIC REFLEX AND THE
LOOMING RESPONSE.
A LOT MORE WORK NEEDS TO BE DONE
THERE.
SO TO SUMMARIZE THE PORTION OF
THE TALK, I TOLD THAT YOU
NEURONAL ACTIVATION CAN BE USED
AS A STIMULUS BUT ALONE IN
COMBINATION WITH OTHER INFO
ABOUT THE BRAIN, IT CAN HELP GET
THOSE TO GET GANG LIAISON AN
CELLS TO GET THOSE BACK IN THE
BRAIN ESPECIALLY WITH YOU BIAS
TOWARD THE INJURED EYE?
THIS MIGHT NOT BE THAT
SURPRISING RIGHT?
MY GREAT GRAND PARENTS,
[INDISCERNIBLE], OBVIOUSLY, MOST
FAMOUS FOR THEIR WORK ON
DISCOVERING THE SPHRUCTURE
FUNCTIONAL RERELATIONSHIPS IN
THE VISUAL SYSTEM AND OCULAR
DOMINANCE PLASTICITY SAID THIS
MUST BE THE CASE, I HAVEN'T
SHOWN THEM THE DATA BUT I MAY
SEE THEM AT THE PEW MEETING, BUT
DAVID PASSED AWAY RECENTLY,
SADLY, THEY WOULD SAY, THERE'S
COMPETITION BUT THE TWO EYES
NEED TO INTERACT CHEMICALLY OR
SYNAPTICALLY BUT WE'RE EXCITED
IT CAN BE USED BECAUSE IT'S
FAIRLY NONINVISITINGIVE AND IT'S
AFTER THE LESION, SO YES WE
DIDN'T OR NO, WE DIDN'T SEE
AXONS GROW ALL THE WAY INTO THE
BRAIN, WHEN WE JUST DID VISUAL
STIMULATION AND WE THEED TO
APPLY OTHER STRATEGIESAs WELL
AND YOU CAN'T IMAGINE A NUMBER
OF CONDITIONS INCLUDING GLAUCOMA
AND CONDITIONS IN WHICH THE GANG
LIAISON AN CELLS MAY NOT HAVE
DEGENERATED BUT WERE MAYBE SICK
OR MAYBE HEALTHY PEOPLE, TO
INCREASE GANG LIAISON AN CELLS
AND HEALTHY AND CONNECT SAID
BECAUSE YOU SAW THE ROBUST
EFFECT OF BLOCKING ACTIVITY.
WE CAN'T FIND THEM IN THE EYE.
SO SOME THING IS GOING ON THERE
AND WE REALLY WOULD LIKE LITTLER
GROUPS TO PICK UP ON THIS AND
RUN WITH IT AS L. WE SAW TARGET
SPECIFIC REENNERIVATION WHICH
SUGGESTS THERE MAY BE
UPREGULATION OF GUIDANCE CUES
AFTER INJURY AND PARTIAL
RESTORATION OF FUNCTION.
ARE WHAT ARE MOLECAR MECHANISMS
OF REGENERATION, WHAT ARE THE
ROLE OF GUIDANCE MOLECULINGS.
WE DIDN'T LOOK AT EVERY GANG
LIAISON AN CELL TYPE.
HOW ACCURATE IS THE WIRING, HOW
DO WE THOSE TO GO BACK TO
TARGETS.
MAYBE SOME TRIED AND FAILED AND
DIED WE DON'T KNOW.
WHY DO THE REINNERIVATES AXONS
RESTORE SOME BUT NOT OTHERS.
THERE WILL BE AN IMPORTANT ROLE
OF SYNAPSE FORMATION OR
REFORMATION, I SHOULD SAY, VERY
LITTLE IS KNOWN ABOUT HOW
SYNAPSE FORM IN THE ADULT BRAIN
AND SYNAPSE REFORMATION AND
THAT'S ANOTHER ONE OF THE CALLED
ARMS FROM THE AGI AND THEN WE
HAVE TO GET FROM MOUSE TO HUMAN.
WHETHER OR NOT THE PRIMATE
SHOULD BE THE MARMA SET OR
MACAQUE MONKEY, IT'S UP FOR
DEBATE.
WE WILL TALK ABOUT THAT, THERE'S
JUST ONE SLIDE, ALEX WHO I
MENTIONED EARLIER, AND I HAVE
TEAMED UP AND LOOKING AT OR NOT
THE SAME MOLECULES THAT ARE
RESPONSIBLE FOR CONNECTING THE
SPECIFIC GANG LIAISON ANS ARE
ALSO TARGETS DURING DEVELOPMENT
AND HE AND I HAD BACK-TO-BACK
PAPERS AND THAT WAS IN 2015
SHOWING IN OUR CASE A ROLE FOR
THE CONTACTINS, CELL ADHESION
MOLECULE AND IN HIS CASE THE
PLEXIN SEMIFORIN MOLECULES AND
CONNECTING TARGETS IN THE BRAIN
STEM.
THIS IS VERY PRELIMINARY BUT
IT'S REPEATED THIS A NUMBER OF
TIMES SO HERE'S A SHAM CRUSH,
CTB LABELING, ALL AXONS AND THIS
IS A LEVEL, THE PROTEIN THAT'S
VERY IMPORTANT FOR CONNECTING
SPECIFIC GANG LIAISON AN DISELS
TO THE TARGETS DURING
DEVELOPMENT, IS KIND OF AT A LOW
LEVEL, AND THIS IS STILL
EXPRESSING IN AXONS BUT AFTER
CRUSH, THEY GO UP LIKE GANG
BUSTERS AT THE SITE, WE DON'T
KNOW, BUT IT DOES SEEM THAT
CRUSHING CELLS INJURYING THEM IS
UPREGULATION AND THIS IS JUST
HIGHER MAGNIFICATION,
UPREGULATION OF THESE MOLECULES
THAT WE KNOW DURING DEVELOPMENT
WERE IMPORTANT FOR CONNECTING
THOSE TO THE TARGET NEGLIGENCE
THE FIRST PLACE, AND WE'RE VERY
INCREEINGED BY THIS WHERE YOU
WANT TO TEST THE FUNCTIONAL
ROLES BY MISS EXPRESSION, TOPIC
EXPRESSION, ONE CAN IMAGINE IN
PATIENTS, POSSIBLY THROUGH A
SERIES OF VERY SELECTIVE
NEUROSURGERIES FAITHING BEADS OR
APPLICATION OF GUIDANCE
MOLECULES, PERHAPS COAXING BACK
LARGE NUMBERS TO THEIR TARGETS
IT WILL BE CHALLENGING BUT IF
THAT'S THE BEST THING THAT IS
AVAILABLE, AND YOU KNOW YOU CAN
DO THAT PERHAPS MAYBE IT JUST
TAKES ONE LONG DISTANCE
ACCUSABLE CUE TO ATTRACT THESE
AXONS WE NEED TO EXPLOAZ THESE
IDEAS IN ANIMAL MODELS FIRST.
AND NOW, THE QUESTION ABOUT HOW
DO YOU FROM MOUSE TO HUMAN.
SO THIS IS AN AREA THAT MY LAB
STUMBLED INTO.
I THINK YOU FIND YOURSELF BACK
IN SILICONE VALLEY AND NEXT
THING YOU KNOW YOU'RE WORKING ON
VIRTUAL REALITY.
AND THAT'S BECAUSE THESE
TECHNOLOGIES ARE ADVANCING VERY
FAST AND BECAUSE I PUT ON THE
RESPONSE TO ONE OF MY COLLEAGUES
SAYING, YOU HAVE TO TRY THIS AND
DISCOVERED IT'S AN ALL-INCLUSIVE
EVENTS AND KIDS WILL DIGS APPEAR
INTO THESE GOGGLES AS TIME GOES
ON BUT ADULTS - IT IS
REMARKABLE, HOW IMMERSIVE IT IS.
AND WE THINK ABOUT HOW WOULD WE
DELIVER VISUAL STIMULATION IN A
WAY THAT'S NOT MONOTONOUS AND
MAYBE ROBUST AND MAYBE IN A MOVE
OR EXPERIENCE THAT THEY WOULD
WANT TO PARTICIPATE IN.
SO WE THOUGHT ABOUT TESTING THE
ROLE OF VISUAL STIMULATION USING
VIRTUAL REALITY, COUPLE REASONS,
ONE IT'S IMMERSIVE AND ENGAGING
AND HARD TO DO IN AN AUDFORMAT
LIKE THIS BUT PLANE OF YOU TRY
IT AND I ENCOURAGE TO YOU TRY IT
IF YOU GET THE CHANCE, THE OTHER
THING THAT CAN YOU DO WITH
VIRTUAL REALITY IS YOU CAN TRACK
EYE MOVEMENTS AND MOVE THE
VISUAL STIMULUS AROUND AND DOING
THIS WITH THE VISUAL STIMULUS IN
ORDER TO DIRECT THE STIMULUS TO
THE RETINA IN WHICH YOU WANT TO
CREATE ELEVATED LEVELS OF
ACTIVITY AROUND LESIONS OR
WITHIN LESIONS, SPECIFICALLY,
AND THEN THE VISUAL RESTORATION
FIELD HAS FOCUSED PREVIOUSLYOT
QUESTION OF WHETHER OR NOT
ENHANCING NEURAL ACTIVITY IN THE
BRAIN OR EYE OR BOTH CAN IMPROVE
VISION AND THERE ARE REPORTS
HERE AND THERE ONE OF THE MAJOR
CRITICISMS OF THAT EFFORT HAS
BEEN THAT PATIENTS CHEAT WITHOUT
KNOWING IT, THEY MOVE THEIR EYES
AROUND A LOT.
THEIR EYES ARE A CAPTIVE
AUDIENCE AND THEY CAN CLOSE
THEIR EYES BUT WE CAN TRACK IF
THEY DO THAT.
SO WE'RE NOW ENTERING, WE HAVE
WRITTEN THE IRBEXPZ WE'RE HAVING
THOSE IRBs REVIEWED OF DOING
TESTING BASE LINE VISION IN A
NUMBER OF DIFFERENT WAYS THIS IS
A COLLABORATION WITH JEFF
GOLDBERG, IN OPTICAL IMAGES THAT
WILL MOLOGY.
WE WILL TALK ABOUT IMMERSIVE.
GENERALLY YOU ENTERTAIN PEOPLE
AND KEEP THEM INCREEINGED NOT 10
HOURS A DAY BAH DRY IT IN A WAY
REGENERATES THIS OR ENGAGES
PLASTICITY AT THE LEVEL OF
CORTEX WE DON'T CARE, WE JUST
WANT TO TO SEE BETTER ANDEN
EVALUATE IMPROVEMENT BECAUSE WE%
DON'T HAVE RESULTS YET, IN A
COUPLE OF YEARS I PROMISE WE
WILL HAVE RESULTS ONE WAY OR THE
OTHER.
HOPEFULLY WITHIN 12 MONTHS, 24
MONTHS FOR SURE.
AND I'M EXCITED THAT
[INDISCERNIBLE] AGI MOVED TO
STAND AFFORD AND--STANFORD AND
USED DIFFERENT OPTICS RANGING
FROM DYSTROPHYS AND LOOKING AT
LETTER CODED VARIATIONS ON THE
DIFFERENT STRUCTURAL FEATURES HE
CAN IMAGE ALT HIGH RESOLUTION IN
THE BACK OF THE HUMAN EYE AND SO
GETTING WAY BEYOND SNELLING
CHARTS AND THEN THE EYE EXAMINE
AND THINGS LIKE HUMPHREYS EXAMS
AND PUSHING WHETHER OR NOT
CERTAIN FORMS OF VISUAL
STIMULATION DIRECTED AT
PARTICULAR LOCATIONS MAY BE IN A
PATIENT THAT HAS, YOU KNOW
SPECIFIC TYPES OF LESIONS, OR
FEATURES WITHIN THE EYE,
DIRECTING VISUAL SIMULATION
RIGHT THERE, AND VR IS A
TERRIFIC WAI TO DO THAT, VERY
HARD TO DO IN OTHER FORMATS.
OKAY, SO I THINK IN THE LAST
COUPLE OF MINUTES, I WANT TIME
FOR QUESTIONS, I WILL GIVE A
TEASER OF WHERE VR CAN ALSO BE
USED SO RATHER THAN GO INTO THE
ANIMAL DATA I WILL QUICKLY SHOW
YOU TWO THINGS, AND I'M MINDFUL
OF THE TIME.
OKAY?
SO, I WANT TO KNOW WHY THIS IS
CARRY AND IF I HAD SMOAD YOU
SOMETHING ELSE, IT MIGHT NOT BE
AND IT HAPPENS EXTREMELY FAST
AND I WANT TO KNOW WHERE IN THE
BRAIN AND HOW IN THE BRAIN IT
HAPPENS AND AT RISK OF GETTING
INTO A WHOLE OTHER CONCEPT
TRAIN, I THINK IT'S INCREDIBLY
INTERESTING QUESTION AND VR HAS
A ROLE TO PLAY AND VISION HAS A
ROLE TO PLAY.
A LOT OF PEOPLE HAVE STUDIED
FEAR BUT NOT MANY PEOPLE HAVE
ADDRESSED WHAT ABOUT VISUAL
STIMULI SPECIFICALLY IS SCARY.
AND SO, THIS IS A SIMPLE EXAMPLE
OF HOW BRIGHTNESS, YOU WOULD
WALK DOWN THIS I DON'T THINK YOU
WANT TO WALK DOWN THIS, YOU
WOULD BE LESS LIKELY, I WOULD
PICK THIS FRANKLY.
THIS USUALLY GENERATES THE
AWWWW-REFLEX, I DON'T WANT TO
TOUCH THIS DOG, SO I WILL
ILLUSTRATE THE ESSENCE OF THE
PROBLEM HERE, AND ALSO, THINGS
LIKE UNJUSTICE ACCESSALATION,
THIS IS ENOUGH TO GET PEOPLE'S
HEART RATE GOING, RIGHT?
WHAT IT IS IS INTERESTING,
IT'S--THIS IS A BEANIE BABY
THAT'S COMING, I DIDN'T WANT TO
SHOW YOU THAT, I THOUGHT WE
WOULD END ON A LIGHTER NOTE, BUT
THE UNDULATION AND MOVEMENT ARE
ALSO VERY INTERESTING FEATURES,
RIGHT?
AND SPEED AND VECTOR ARE OFTEN
WHAT'S SCARY.
UNDULATION LEADS TO UNPREDICT
DIBL ABOUT WHAT DIRECTION
SOMETHING IS GOING TO GO AND IT
CAN MOVE FAST AND QUICKLY IN ONE
DIRECTION, THAT'S SCARE EXPE
THERE IS GOES UNFORTUNATELY THE
BEANIE BABY DOESN'T MAKE IT, THE
OKAY, YEAH, SO, JUST VERY
BRIEFLY AND I WILL TRULY SKIP
OVER THE SLIDES BECAUSE I'M
HAPPY TO TALK ABOUT THIS
OFFLINE, BUT THIS IS--LET ME
JUST SHOW THE BEHAVIOR THAT WAS
REALLY BEAUTIFULLY SET UP
FOR--THERE'S BEEN A LOT OF
DISCUSSION, THIS DOVETAILS ON
REGENERATION IN A WAY,
VISUALIZATION IS HARD TO PROBE
BUT SOME ARE ROBUST, IT WAS
DISCOVERED BY A GRADUATE OF
MARCUS M, ISTER 'S LAB, AND NOW
SHE'S IN MY LAB, SHE'S STUDYING
VISUAL FEAR IN HUMANS THIS, IS
THE FIRST TIME AND EVERY TIME
VISUAL LOOM IS PRESENTED.
IT GETS SCARED AND LOOK AT, THIS
IS AN ACTIVE PROCESS, IT ALMOST
LIKES LIKE IT FROZE IN THE MOVIE
OR THE MOUSE MIGHT DO THIS.
RUN, HIDE.
NOT SO HIDDEN I'M GOING TO GET%
OUT OF HERE, OKAY?
ONE OF THE TWO EVERY SINGLE TIME
SO I DON'T WANT TO GET INTO THE
DETAILS OF ALL THIS, WHAT I WILL
TELL YOU IS TWO TEASERS AND THEN
WE WILL MOVE TO QUESTIONS WE
HAVE A LOT OF MECHANISM
MECHANISM--MECHANISTIC DATA BUT
FORGIVE ME FOR SKIPPING A LOT OF
THIS BUT LINDSAY HAS IDENTIFIEDA
I NUCLEUS CONNECTED TO THE
PATHWAY THAT WHEN STIMULATED
CONVERTS FEAR INTO WHAT IS
ARGUABLY AGGRESSION, TAIL
RATTLING IN MICE IS WHEN YOU PUT
THEM TOGETHER AND FIGHT, IT'S
LIKE CHEST THUMB NOTHING
PRIMATES OR GUYS IN BARS THAT
HAVE A FEW TOO MANY AND GO AT
AND NOT A GOOD DECISION, RIGHT?
SO HERE SHE'S STIMULATING THE
THAM ALIC AREA, WITH CHEMICAL OR
CAN DO THIS WITH OPTICAL IMAGES
O GENETICS IT FREEZES FOR A
MOMENT AND THEN IT WALKS AROUND
AND TAIL RATTLING IF IT'S NOT
AGGRESSION, MAKE THIS IS MOUSE
MORE SALIENT TO THE STIMUE
LUGZULOUS, THIS MOUSE IS
COMFORTABLE STROLLING AROUND AND
RATTLING ITS TAIL AGAINST THE
WALL AND IT WILL CONTINUE TO DO
THIS OVER AND OVER AGAIN.
AS LONG AS SHE'S STIMULATING
THIS NUCLEUS, I'M INCREEINGED BY
THIS, HOW AND WHY IS IT THAT THE
CERTAIN SENSATIONS WITH A SINGLE
VISUAL PATHWAY CAN CONVERT ONE
SENSATION INTO ANOTHER KIND OF
OF EMOTIONAL RESPONSE,
BEHAVIORIAL RESPONSE.
SO I DON'T WANT TO SPEND TOO
MUCH TIME ON THIS BUT WHAT I
WILL TELL SURVEYS THAT WE'RE
BACK NOW V. R. BECAUSE WE'RE
USING THIS ANN EMERCKIVE WAY TO
PROBE VISUAL FEAR IN HUMANS AND
ACTUALLY THIS IS STEVE BECKER,
HE'S OWLLY ON--UP ON A PLATFORM,
MANY METERS ABOVE THE GROUND,
HE'S ON THE FLAT OF MY LAB.
THIS IS MICHAEL MULLER, IF YOU
EVER SEEN THIS CELEBRITY
PHOTOGRAPH OR MBBA OR OLYMPIC
PHOTOGRAPH, HE TOOK IT AND
MULLER HAS A THING FOR
COLLECTING MOVIES AND HE LIKES
SHARKS SO HE AND HIS BUDDIES
LIKE TO SWIM OUTSIDE THE CAGE IN
GUADALUPE, HE LIKES TO DRESS
LIKE A TOWN - SO THEY COME CLOSE
TO HIM AND THEY WENT AND GOT US
IMMERSIVE V. R. FOOTAGE AND HERE
STEVEN'S NOT LOOKING AT THE
SHARK THING I'LL USE HIS BODY
LANGUAGE, I'LL TURN OFF THE
SOUND AND IS--YOU KNOW THIS IS
HIS RESPONSE, HE THINKS HE'S
ABOUT TO FALL OFF A BRIDGE.
LET ME SEE IF I CAN TURN UP THE
SOUND, MAY I DO THIS?
I'LL ASK PAUL?
CAN I--HE AGREED TO THIS.
SO I DON'T WANT THIS TO GO TOO
LEWD.
>> LET ME IF I CAN.
>> OH MY GOD--SO THAT'S
ESSENTIALLY, THE OH MY GOD
RESPONSE.
NOT AN UNUSUAL ONE TO FEAR.
SO, WHAT'S INTERESTING ABOUT
THAT TO ME IS THAT IT'S SO
IMMERSIVE, HE KNOWS HES IN THE
LAB AT SOME LEVEL BUT THE BRAIN
THINKS HE'S UP ON THE PLATFORM
AND THERE'S NOTHING UNUSUAL
ABOUT THAT RESPONSE.
EVERYONE THINKS THEY'RE WITH THE
SHARKS WHEN YOU PUT THIS ON AND
JUST TO ILLUSTRATE, YOU CAN
IMAGINE DOING A VISUAL PARADIGM,
MAYBE NOT SCARING PEOPLE BUT
WALKING THROUGH THE SYDNEY OPERA
HOUSE IN VIRTUAL REALITY, I TOOK
OFF THE GOGGLES ON THAT ONE AND
I ACTUALLY WANT TO GO TO THE
REAL OPERAEROUS AND I DON'T WANT
TO SPOIL THE EXPERIENCE, SO IT'S
SO IMMERSIVE AND A PORTABLE
CLINIC AND WE'RE THINKING PROBE
AND STIMULATE REGENERATION IN
THE VISUAL SYSTEM AND LAST BUT
NOT LEAST, THIS IS A NEW
COLLABORATION WHERE IT'S GREAT
TO RECORD BEHAVIORIAL RESPONSES
AND SOPHISTICATEDMATIC RESPONSES
AND GALVANIC SKIN RESPONSE AND
ECG AND THINGS LIKE THAT FROM SO
CALLED NORMALS OR HEALTHY
INDIVIDUALS LIKE STEPHEN OR BUT
IT'S ALSO GREAT OPPORTUNITY NOW
THAT EDDIE CHANG, COLLEAGUE UP
UP AT UCSF, THEY HAVE PATIENTS
HAVE ELECTRODES EMBED INDEED
THIS SIGNALS AND THESE ARE
SIGNALS WHILE A PATIENT VIEWS
FROM THE AMYGDALA FROM A GREAT
WHITE SHARK AS IT'S PASSING
THROUGH HIS VISUAL FIELD SO WE
CAN GET NEURAL EVENTS TO
SOPHISTICATEDMATIC RESPONSES TO
BEHAVIORIAL RESPONSES AND THEN
SUBJECTIVE REPORTS AND THAT'S
WHERE WE'RE HEAD INDEED A MAJOR
WAY IN THE NEXT COUPLE OF YEARS
YEARS
AND THESE EFFORTS REGENERATION
AND VISUAL FEAR ULTIMATE GOAL
MAYLY AS A WAY TO PROBE THINGS
LIKE ANXIETY AND PTSD ARE WHERE
I WILL PUT MOST OF MY LAB'S
EFFORTS, WE WILL CONTINUE WITH
THE DEVELOPMENT WORK OF COURSE.
SO I WILL FINISH THERE.
I THINK WE'RE ON THE HOUR.
SO I WANT TO THANK THE PEOPLE
WHO KRIEWBILITY TO THIS WORK,
LINDSAY SALAY, FABULOUS GRADUATE
STUDENT.
STAY TUNED TO THE MECHANISTIC
FEATURES OF CONVERTING SCARED
MICE INTO BRAVE MICE.
ALBERT LIM, AND CURRENTLY AT
GENENTECH, AND THEN REGENERATION
IF THE BRAIN, CORTICO
PLASTICITY, MELIS YILMAZ, IN THE
LAB, WORKING ON THE THESE AND
I'M VERY GRATEFUL TO THESE FOLKS
AND THE FOUNDATIONS FOR FUNDING
AND NONE OF THE WORK WE COULD
HAVE DONE WOULD HAVE HAPPENED
WITHOUT THE SUPPORT OF THE NEI
AND NIH.
THANK I SO MUCH AND I APPRECIATE
YOU--THANK YOU SO MUCH AND I
APPRECIATE YOUR ATTENTION.
[ APPLAUSE ]
I WILL BE HAPPY TO ANSWER
QUESTIONS BUT I REALIZE SOME MAY
HAVE TO LEAVE GIVEN THAT WE'RE
ON THE HOUR.
YES?
>> SO PATIENTS WHO ARE
[INDISCERNIBLE] THE MTOR MIGHT
BE [INDISCERNIBLE]
[INDISCERNIBLE] SO THE QUESTION
IS WHETHER OR NOT IN GLAUCOMA
PATIENTS WHO ARE LOSING GANG
LIAISON AN CELLS WHETHER THE
MTOR THERAPY WOULD HELP SLOW
THAT LOSS OR REGENERATE GANG
LIAISON AN CELLS.
I'M NOT A CLINICIAN BUT I WILL
SAY THIS, THE ANIMAL DATA SAY
YES, I THINK IT'S IMPORTANT TO
REPLICATE THESE RESULTS FIRST
DISCOVERED BY KEVIN PARK AND
OTHER SAYS HAVE REPLICATED, OF
COURSE, IN A PRIMATE MODEL.
I THINK IT WILL BE VERY
IMPORTANT.
OF COURSE THERE'S EFFICACY AND
SAFETY ISSUES RELATED TO
INCREASING MTOR BECAUSE THE
CANCER BIOLOGIST MIGHT LEAP OUT
OF THEIR SEATS AND COMUP TO THE
PODIUM IF I SAY LIKE LET'S PUT
IN RHEB VIRUS BECAUSE THE CELLS
GROW VERY LARGE, WE DO KNOW THEY
MAINTAIN THEIR RECEPTIVE FIELDS
SO PROVIDED YOU CAN BYPASS OTHER
DELETERIOUS POTENTIAL EFFECTS OF
INCREASING MTOR, YES.
I BELIEVE THAT THAT'S A PATHWAY
THAT'S WORTH LOOKING INTO AND
SERIOUSLY IN THE CLINICAL REALM.
WHETHER OR NOT IT'S THROUGH PEP
TIDES OR WHETHER OR NOT IT'S
GOING TO BE THROUGH A GENETIC
STIMULUS, MAYBE YOU WANT MTORON
FOR A FEW HOURS EACH DAY AND THE
GENETIC TEALS THAT ARE AVAILABLE
NOW ALLOW YOU TO DO THESE KIND
OF SHORT DURATION PULSES OF GENE
ACTIVATION, BUT WE--I THINK THE
PRIMATE MODELS WILL GIVEN THE
SIMILARITIES OF THE EYE AND
ARCHITECTURE AND LONG DISTANCES
OF COURSE THEY HAVE TO GO
THROUGH THE STANDARD TRIALS BUT
I WOULD PUT MY MONEY ON IT IN
TERMS OF HAVING A STRONG EFFECT
AND WHETHER OR NOT CAN YOU AVOID
SIDE EFFECTS IS THE KEY ISSUE.
IN THE CRASH MODEL YOU LOSE THE
AXONS, SO IN MOST HUMAN DISEASES
AND MOST HUMAN DISEASES THAT
EFFECT THE OPTIC NERVE, THAT
CLASS IS MORE GRADUAL.
SO IS THERE A POSSIBILITY THAT
THE REMAINING AXON SCAN HELP IN
THIS REGENERATION PROCESS?
>> GREAT QUESTION.
SO, YOU KNOW THERE WAS A LOT OF
DEBATE ABOUT WHAT MODELS TO USE
IN GLAUCOMA, DBA-TWO-J, BEAD
MODEL, PRESSURE.
IT'S INTERESTING.
THE FIELD FROM THE PAPERS I
REVIEW AND SEE AND SUBMIT IS
KIND OF SAID, YOU KNOW THEY ALL
HAVE THEIR VALUE.
SO THE I THINK THAT'S A GOOD
PROGRESSION, WE NEED MORE PEOPLE
IN THE FIELDS AND NEED TO USE
MORE MODELS, PEOPLE ARE SHARING
REAGENTS MORE AND PEOPLE ARE
SENDING PEOPLE BETWEEN LABS, WE
CERTAINLY TAUGHT PEOPLE THE BEAD
MODEL AND WE LEARNED IT FROM
OTHERS AND THERE'S MORE SHARING
WHAT HASN'T HAPPENED YET,
CULTURALLY IF YOU WILL.
AND I WOULD LIKE TO SEE MORE OF
IS INDIVIDUAL LABS USING
MULTIPLE MODELS, SO WE USE THE
BEAD MUDDLE AND CRUSH MODEL BUT
WE HAVEN'T USEDDED BEAD MODEL IN
REGENERATION BUT WE'RE DOING
THAT NOW.
THE CRUSH MODEL HAS THE
DRAWBACKS BUT TO ANSWER YOUR
QUESTION MORE DIRECTLY.
THE PHYSICAL PRESENCE OF OTHER
AXONS WE KNOW DURING DEVELOPMENT
ACTS AS A GUIDE FOR SUBSEQUENT
AXONS TO USE THIS, THE
PIONEERING EFFECT OR AXONS AND
EVERYTHING WE SEE FROM THE ROLL
OF ACTIVITY TO THE ROLL OF
MTORTO--I'M DRAWING A BLANK CSPG
REGULATION THAT WE SEE DURING
DEVELOPMENT AS A POSITIVE IMPACT
OF GROWTH OF GANG LIAISON AN
CELLS HAs A POSITIVE IMPACT OF
REGENERATION OF GANG LIAISON AN
CELLS SO PHYSICAL SUBSTRATES FOR
GROWTH MATTER DURING DEVELOPMENT
BUT I WILL BE WILLING TO BET
THAT THE PHYSICAL SUBSTRATE FOR
GROWTH WILL HELP IN THE ADULT
AND I JUST HOPE SOMEONE DOES THE
EXPERIMENT.
YOU KNOW WE WILL DO, HOW DO I
SAY THIS.
I WILL SAY THE WAY IT IS WE WILL
DO AS MANY EXPERIMENTS AS I CAN
MAY MY PEOPLE TO DO WELL BUT
THERE'S A THRESHOLD TO THAT.
>> THANK YOU.
>> THE FUNDING AND THE WELL PART
SO WE NEED MORE GROUPS WORKING
ON THESE THINGS.
THANKS FOR THE QUESTION.
>> HI, YOU MENTIONED GLIAL SCAR
REAL QUICKLY, HOW IMPORTANT DO
YOU THINK THE GLIAL SCAR IS IN
THE OPTIC NERVE CRUSH MODEL IN
STOPPING AXONAL REGENERATION.
>> THE WORD WORD ANSWER IS VERY.
IT'S INTERESTING THAT INTRINSIC
STIMULATION ALONE, YOU CAN GET
AXONS REGENERATING THROUGH
LESION SITES BUT NOT INTO THE
BRAIN.
BUT THEY DO REGENERATE BUT NO
ONE HAS DONE THE COMBINED
NEUTRALIZATION OF A GLIAL
SECRETED FACTOR AND MTOR, TO MY
KNOWLEDGE, FORGIVE ME IF I'M
MISSING A PUBLISHED REPORT.
PLEASE SEND IT TO ME IF I MISS
TODAY, IN CONJUNCTION WITH THE
ANGRY E-MAIL I USUALLY GET BUT I
WANT TO KNOW THE LITERATURE.
IF IT'S OUT THERE, I APOLOGIZE,
SO I DOABILITY THINK IT'S BEING
DONE EMPLOY BUT THAT'S AN
IMPORTANT PONENT, BUT THEY
REALLY HAVE--THEY GOT PEOPLE
TOGETHER AND SAID WHAT ARE THE
CRITICAL ISSUES AND WE DON'T
KNOW THE FUNCTIONAL ROLE OF
GLIAL SCAR WHEN COMBINED WITH
INTRINSIC GROWTH PROMOTERS BUT
WE HAVE TO FIGURE THAT OUT.
>> DO PEOPLE KNOW WITH WEATHER
THERE'S GLIAL SCAR FORM NOTHING
THE CRUSH MOUSE MODEL.
>> YTS IT'S, YES IT'S ALSO
SETTING UP A PHYSICAL BARRIER.
NOT WORK WE'VE DONE BUT OTHER
GROUPS INCLUDING GROUPS HERE.
>> HI,.
>> HI,.
>> IM CURIOUS IN YOU LOOK AT
THE HEALTH OF THE TARGETING
SYSTEMYS IN SO IF YOU LESION AND
GET RID OF THERE--RETINAL GANG
LIAISON AN CELLS AND THEN THE
DOWN STREAM EFFECT OF THE HEALTH
OF THE TARGET FOR AS A POTENTIAL
REASON FOR WHY IT'S NOT
REFORMING.
>> GREAT QUESTION.
AND THE SHORT ANSWER IS WE
HAVEN'T, VERY FEW PEOPLE HAVE.
THERE'S A REAL DIRTH ROLE OF
WORK LOOKING AT THESE.
WHEN YOU DENERVATE A TARGET
DEVELOPMENTALLY.
GOING BACK TO DEVELOPMENT.
WE GET ANY CLUES IT'S THE
FOLLOWING, IF YOU DENERVE A
TARGET DEVELOPMENTALY, THE
SYNAPTIC TRANSMISSION IS ONE OF
THEM AND THE NEURON THERE IS
SHRINK THEIR OUTPUTS DEGENERATE
TO SOME DEGREE.
THIS IS THE LATE LARRY CATS DID
BEAUTIFUL WO, ON THIS.
HE SHOWED IF YOU DEPRIVE THE
NUCLEUS OF INPUT BUT YOU SUPPLY
IT WITH GROWTH FACTOR WITH THE
PROJECTION THROUGH THE CORTEX,
PUTTING BEADS IN AND THAT THINGS
OF THAT SORT, YOU CAN PRESERVE
THE GENERICULATEAND THERE IT WAS
ALSO SHOWN THAT IF YOU CLOSE ONE
EYE, THERE'S A SHRINKING OF THE
DEPRIVED EYE LIERS, BUT IN THE
NONDEPRIVED EYE LAYERS SO WE
NEED MORE WORK BUT ALMOST
CERTAINLY YES.
>> HI, SO, I'D BE CURIOUS TO
HEAR YOU SPECULATE A BIT MORE
ABOUT THE MECHANISM BY WHICH
CONTRA LATERAL DEPRIVATION IS
SIGNALING SO FOR EXAMPLE, IF YOU
WERE TO TAKE SAY, A CHUNK OF
RETINA AND OPTIC NERVE THAT ARE
STILL ATTACHED, AND PUT THEM
INTO A HOST, DO YOU THINK THAT
THERE WOULD BE--YOU KNOW, IN THE
PERO NEUROECTODERMAL UMKC OR
VENTRICLE OR CIRCULATING CUES
ESSENTIALLY.
ARE YOU SEEING SOMETHING LIKE
THAT?
OR'RE YOU THINKING IT'S
INFORMATION COMING ALONG THE
PATHWAY?
ET CETERA?
>> I HAVEN'T THOUGHT ABOUT WHAT
YOU'RE DESCRIBING BUT
TRANSPLANTATION CAN REVEAL A
LOT.
JEFF GOLDBERG DID A EXPERIMENT
THAT GETS AT THIS A BIT.
HE TOOK REALLY YOUNG CELLS THAT
ORD NARRLY WOULD GROW IN A DISH
OR INVIVO. AND IN HIS SCIENCE
PAPER BUT IT WAS SUPPLEMENTAL
DATA EAR HIDDEN IN THE KIND OF
END OF PAPER, IT WAS A CRITICAL
EXPERIMENT AND HE PUT IT INTO
THE ADULT CORPUS CO LOSS UMKC.
THE MILLUE IS TERRIBLE FOR
REGENERATION AS FAR AS WE KNOW.
AND THEY EXTENDED AT A FAST
GROWTHERATE.
SO IT'S CREATING A PERIPHAL LIKE
THING EXCEPT IN REVERSE, YOU
TAIB A BABY NEURON AND PUT IT IN
A BAD ENVIRONMENT AND IT GROWS.
SO THAT SUGGESTS THAT IT'S
SOMETHING REALLY INTRINSIC TO
THE NEURONS THAT'S ACTIVATED BUT
IN THIS ARRANGEMENT OF BIASED
VISUAL STIMULATION, MTORAND SO
FORTH, IT'S HARD TO IMAGINE
MANAGE THAT'S BASED ON LOCAL
ENVIRONMENT, THE DATA KIND OF
POINT TO SOMETHING DIFFUSIBLE
BUT NOT PURELY DEFUSE ABLE
BECAUSE WE DID EXPERIMENTS IN
WHICH ALBERT REVERSED THE
DIRECTION OF TREATMENT SO HE'S
CLOSING NOW THE TREATED EYE AND
HE'S INJECTING THE OTHER EYE AND
HE DIDN'T SEE THE SAME REESKT
EFFECTS SO WHAT I THINK WE NEED
TO DO IS SOME NICE RNA SEEK,
GROWTH STIMULATE GANG LIAISON AN
CELLS AND FORTUNATELY, WE HAVE
SUPPORT TO DO THAT.
THERE'S A GRANT THAT INVOLVES
HOLLY KLEIN, JEFF GOLDBERG AND
LARRY BENOWITS AND LOOKING AT
THESE TRANSSCRIMENT OHMS OHMS
AND
PROTEIN COMPLEX I DON'T MEANS
AND WE WON'T NECESSARILY GET THE
CUE THAT WAAND MIGHT GET THE
RECEPTOR OR SOME HINTS INTO WHAT
THE QR.
IF ANY OF HAVE YOU IDEAS ABOUT
THIS OR WANT TO PURUE THE LINE
OF EXPERIMENTS THIS WILL NOT BE
A SINGLE LAB OR QUADLAB EFFORT.
ONE BRIEF POINT IN THE SPINAL
CORD, THERE'S INCREEINGING
LITERATURE THAT SUPPORT THIS IS
IDEA OF BIASED USE.
ONE OF THE BEST TREATMENTS FOR
GETTING PLASTICITY IS TO TIE UP
THE GOOD LIMB AND FORCE USE OF
THE IMPACTED LIMB TO DRIVE--THE
OLD WHERE SOME OF YOU MAY
RECALL, I REALLY LOVE THIS
STUFF, TIM SHALLERT, WHO WAS THE
UT AUSTIN AND POPULARIZED THE
EFFECT OF TYING UP THE GOOD LIMB
AND THEN THAT WAS PICKED UP ON
BY A NUMBER OF DIFFERENT
LABORATORIES INCLUDING MARTIN
SCHWAB'S LAB.
I WILL SKIP BACK AND NORTH FOR
THE LAST TWO QUESTIONS.
>> HAS HAS [INDISCERNIBLE] BEEN
TRIED IN FISH NEURONS WHERE THEY
CAN REGENERATE THE EFFECT OF
MTOR, P10, ET CETERA?
>> NOT TO MY KNOWLEDGE AND YOU
KNOW OF COURSE IN FISH THEARKS
ADDING NEW NEURONS ALL THE TIME.
>> LIKE A KNOCK OUT OF MTOR.
I DON'T WANT TO PUT HER UP TO AN
EXPERIMENT THAT SHE'S NOT DOING
FOR WHATEVER REASON YOU BUT I
THINK
HOLLY IS DOING THESE EXPERIMENTS
BECAUSE OF COURSE SHE HAS SUCH
BEAUTIFUL DECADES OF BEAUTIFUL
WORK IN THE FISH AND XENAFIS,
AND THERE YOU WOULD EXPECT THAT
MTORWOULD BE HIGH IN THESE BABY
NEURONS AND THAT MIGHT BE THE
REASON WHY THEY CONTINUALLY
REGENERATE.
THAT QUESTION IS STILL SO
FUNDAMENTAL WE DON'T KNOW WHY
THESE COLD BLOODED VERTEBRATES
REGENERATE BUT IT'S SCREAMING
MTOR.
SO THAT'S EXACTLY THE RIGHT
QUESTION.
YEAH.
>> THANK YOU.
>> WE HAVEN'T DONE IT.
I'M TRYING TO KEEP THE NUMBER OF
SPECIES TO--ALTHOUGH IT WOULD BE
EASIER TO WORK ON FIB THAN
HUMANS BECAUSE IT TURP OTHER
THAN OUT THAT'S COMPLICATED
[LAUGHTER]
>> I WAS CURIOUS IN YOU HAVE ANY
SENSE OF IF YOU CATERED OR IF
YOU TAYLOR THE STIMULUS TO WHAT
MAYBE SOME TYPE OF GANG LIAISON
AN CELL FIRST, WOULD YOU RECRUIT
MORE OF THOSE TYPES OF GANG
LIAISON AN CELLS, LET'S SAY IF
YOU HAVE MORE LOOMING, WOULD YOU
GET MORE LUMENS, OR CELLS TO GO
BACK TO THE BRAIN OR IN A--
>> GREAT QUESTION.
THE EXPECTATION IS YES, BECAUSE
THOSE Ls ARE GOING TO SPIKE
MORE IN RESPONSE TO A PARTICULAR
STIMULUS SO WE'RE DOING THOSE.
YOU KNOW IT'S VERY PRELIMINARY
BUT WE THINK THAT THIS IDEA THAT
ONLY SOME GANG LIAISON AN CELLS
CAN REGENERATE BECAUSE OF
SOMETHING THAT'S SPECIAL ABOUT
THEM MOLECULARLY, IT'S TRUE,
BEAUTIFUL WORK FROM JOSH AND
OTHERS TO SHOW THAT THE ALPHA
CELLS REGENERATE PARTICULARLY
WELL AND THAT HAS TO DO WITH THE
EXPRESSION OF IGF-ONE.
BUT IN OUR TREATMENT, WE SAW
RECOLLECT CELL TYPES THAT
REGENERATE AS WELL.
AND WHEN WE START RECRUITING
THEM THROUGH VISUAL ACTIVATION,
THIS IS ANOTHER REASON WHY WE
REALLY WANT TO TRY THIS IN
HUMANS AND TAYLORS THE TYPES OF
VISUAL DEFICITS DEFICITS AND
THOSE
DEFICITS THAT THE PEOPLE HAVE,
WE THINK THAT'S GOING TO BE THE
CASE, AND AGAIN, VR IS A
PERFECTLY GOOD WAY.
WE KNOW THESE PEOPLE ARE
DEFICIENT IN MOTION PERCEPTION
AND WE THINK THAT IT'S MOTION
PERCEPTION DUE TO LOSS OR INJURY
OF GANG LIAISON AN CELLS IN THE
VISUAL FIELD.
VR IS THE PERFECT PLATFORM TO
DELIVER TO THOSE LOCATIONS OR
AROUND THE LESION, PERHAPS YOU
WANT THOSE OR BI POLEAR CELLS
CAN RECRUIT THE MOTION SENSITIVE
CELLS.
OR MOTION SENSITIVE CELLS AND
ALL THAT CAN BE DONE IN VR IN A
STRAIGHT FORWARD WAY, DIDN'T
REQUIRE DEVELOPMENT OF A DRUG
TARGET OR TOOL, SO WE'RE EXCITED
TO PURSUE THAT.
>> OKAY, THANK YOU ANDY YOU
STIMULATED A LOT OF CONVERSATION
HERE, THANK YOU FOR COMING.
GOOD LUCK WITH MTOR, AND ALL OF
THE MOLECULES THAT WE WILL BE
USING IN PEOPLE SOMEDAY, THANK
YOU.
