Neural Plasticity - From synapse to perception

>> GOOD AFTERNOON, EVERYONE. WELCOME TO WALS. I'M A VISITING FELLOW IN NIDCD. TODAY IT IS MY GREAT HONOR TO INTRODUCE MU-MING POO FROM THE UNIVERSITY OF CALIFORNIA AT BERKELEY NOMINATED BY NIH POSTDOC FELLOWS AND HERE I WANT TO ENCOURAGE ALL THE FELLOWS TO NOMINATE YOUR FAVORITE SCIENTIST AND YOU MAY HAVE A CHANCE TO HOST THEM. DR. MU-MING POO RECEIVED HIS BACHELOR DEGREE IN PHYSICS IN 1970 FROM TAIWAN AND PH.D. FROM JOHN'S HOPKINS IN 1974. GIVEN BY HIS PHYSICAL BACKGROUND, HE HAS VERY INTERESTING PERSPECTIVE TO STUDY NUREE SCIENCE AND HAS BEEN COUNTED BUTING ENORMOUS FIELDS. IN 70s, HE DE+ELOPED A NUMBER OF TOOLS TO STUDY THE MOBILITY AND LOCALIZATION OF PROTEINS IN CELL MEMBRANE DURING THE 80S HE DEVELOPED NOVEL USES OF RECORDING METHODS IN STUDYING TRANSMETER SECRETION A'D SNAPPED GENESIS. DURING 90S, HE MADE MAJO) CONTRIBUTIONS TO OUR UNDERSTANDING OF EXON GUIDANCE AND SYNAPTIC PLASTICITY AND HE MADE NOVEL USE OF CELL CULTURE SYSTEM TO STUDY THE LAW OF NEURO. [ INDISCERNIBLE ] IN REGULATING ACTIVITY DEPENDENT SYNAPTIC MODIFICATION. MORE RECENT STUDIES ALSO BEEN CONTRIBUTED TO FORMULATION OF THE IDEA OF TIMINt DEPENDENT PLASTICITY AND THIS ARTICLE HAS BEENCYTED OVER THOUSANDS OF úAND THIS IS ALSO THE TOPIC SHE TEAMS. GOING TO COVER TODAY. DR. POO IS RECIPIENT OF AWARDS AROUND THE WORLD. JAPANESE NEUROSCIENCES INVESTIGATOR AWARD FROM NIH. [ INDISCERNIBLE ] FROM PARIS, PEOPLE PUBLIC CHINA, INTERNATIONAL SCIENCE AND TECHNOLOGY OPERATION. HE IS (U)RENTLY MEMBER OF ACADEMIA SENECA IN TAIWAN, MEMBER OF NATIONAL ACADEMY OF SCIENCES IN THE STATES AND ALSO A FOREIGN MEMBER OF CHINESE ACADEMY OF SCIENCES. DURING HIS LONG SUCCESSFUL CAREER, DR. ñOO HAD SERVED SEVERAL FACULTIES IN TOP UNIVERSITIES AT UNIVERSITY OF CALIFORNIA AT IRVINE. [ INDISCERNIBLE ] AND COLUMBIA BEFORE HE JOINED BERKELEY IN 2000 WHERE HE IS CURRENTLY DISTINGUISHED PROFESSOR IN BIOLOGY. IN 1999 HE COFOUNDED AN INSTITUTE OF NEUROSCIENCES AND HAS BEEN SERVING THE DIRECTOR EVER SINCE. THISINS INSTITUTE A NEUROSCIENCES PROGRAM IN CHINA AND ALSO WHERE HE IS NURTURING THE NEXT GENERATION OF NEUROSCIENTISTS. I VERY PROUD TO SAY I GRADUATED FROM THIS INSTITUTE THREE YEARS AGO SO IT IS REALLY GREAT TO SEE DR. POO AGAIN. AND THANK YOU FOR COMING. TODAY HE IS GOING TO TALK ABOUT NEUROPLASTICITY FROM SYNAPSE TO PERCEPTION. PLEASE JOIN ME IN WELCOMING DR. POO. [ APPLAUSE ] >> THANK YOU VERY MUCH. IT WAS A GREAT HONOR TO BE INVITED BY FELLOWS. I'M GOING TO TELL YOU A FEW STORIES ON THE NEUROPLASTICITY. AS YOU KNOW, THE MOST REMARKABLE FEATURE OF THE BRAIN IS THE PLASTICITY, THE ABILITY TO EXPERIENCE.ESPONSE TO IT MAKES A HUMAN CAPABLE OF REMARKABLE ABILITY OF RESPONDING TO ENVIRONMENT AND CHANGING ENVIRONMENT. THE PLASTICITY OF THE BRAIN STARTS WITH THE ACTIVITY. IT TURNS OUT THAT ELECTRICAL ACTIVITY IS THE MOST POST ENT WAY OF CHANGING THE BRAIN STRUCTURE AND FUNCTION. ACTIVITY ASSOCIATED WITH THE SENSORY AND MOTOR FUNCTION OR ASSOCIATED WITH COGNITIVE EXPERIENCE, WILL ALTER THE FUNCTION OF THE SYNAPSE AND THE NEURONS IN SUCH A WAY THAT THE FUTURE ACTIVITY THROUGH THE. [ INDISCERNIBLE ] THE LEARNING AND MEMORY DUE TO THE EXPERIENCE WILL IMPRINT THE STRUCTURE OF THE BRAIN SO THAT THE COGNITIVE FUNCTION AND BEHAVIORAL WILL BE ALTERED. THE QUESTION HAS BEEN, OVER THE LAST CENTURY, HOW THE ACTIVITY EFFECTS THE NERVOUS SYSTEM. THE IDEA THAT THE DIRECT ACTIONS ON THE áV'APSE AND ON THE NEURON ITSELF, THIS IDEA HEADS BEEN OR HAS A LONG HISTORY BUT THE PERSON WHO MOST EFFECTIVELY SUMMARIZED AND PROPOSED THE PROBLEM Rj CANADIAN PSYCHOLOGY. ALTHOUGH HIMSELF IS NOT A PHYSIOLOGIST THE COGNITIVE FUNCTION CAN BE EXPLAINED BY PHYSIOLOGICAL MECHANISMS. SO IN A BOOK PEE HUB ENGLISHED 1949, HE PROPOSED A HYPOTHESES. THIS IS KNOWN AS. [ INDISCERNIBLE ] IN THIS HYPOTHESES HE SAID THAT THE PERCEPTUAL EXPERIENCE CHANGED THE NERVOUS SYSTEM BY CHANGING THE SYNAPSE. NOW -- EXON OF A NEURON -- OF A CELL A, IS NEAR ENOUGH TO EXCITE CELL B AND REPETITIVELY AND TAKE PRIDE IN FIRING THE CELL. THEN THE ISN'T SICK TREATED. [ INDISCERNIBLE ] THROUGH CHANGES IN METABOLISM AND GROWTH AND STRUCTURE CO-RELATED ACTIVITY. IN A PRESYNAPTIC CELL AND POST SYNAPTIC CELL. THIS LITERAL IDEA OF THE SYNAPSE. THIS IDEA WAS EXTENDED IN THE 70S FOR SYMMETRY. IF THE ACTIVITY STRENGTHENS SYNAPSE -- [ INDISCERNIBLE ] THEN WE HAVE A NICE ASSEMETRY IN THIS HYPOTHESES. NOW THIS IDEA IS BECOME VERY POPULAR. WE NOW ALL SAY THAT NERVOUS SYSTEM CELLS THAT FIRE TOGETHER WIRE TOGETHER. THIS IS THE SIMPLE RULE THIS SILENT INTERESTING HYPOTHESES T HELPS US TO UNDERSTAND SIN APP ACTIVITY DEPENDENT PROCESS IN THE BRAIN, ESPECIALLY IN EARLY DEVELOPMENT. NEURO EARLY DEPARTMENT AND EARLIER CONNECTION WILL BE REFINED BY EXPERIENCE NOW FOR EXAMPLE, THE BEST EXAMPLE IN TERMS OF LEARNING THIS RULE, IS THE DEVELOPMENT OF THE MAPPING. THE NEURONS SENSE EXON FROM RETINA, THE GANG LA CELL EXON, MAY CONNECT EXON FROM RETINA AND TEMPORAL EXON GOES THROUGH THE INTERLEND AND THE NASAL EXON GOES TO THE POSTERIOROR IN ODD PROJECTION. NOW THIS PROJECTION IS ESTABLISHED GRADUALLY IN DEVELOPMENT. IN EARLY DEVELOPMENT, THIS PROJECTION APPEARED TO BE DETERMINED BY GRADIENTS OF MOLECULES IN THE NERVOUS SYSTEM. THERE IS MENTION ON THE CELLS THAT MATCHES GRADIENTS OF MOLECULES IN THE TECTUM. RECEPTORS HAS A GRADIENT IN TECTUM CELL -- [ INDISCERNIBLE ] THERE IS A LIGAND WHICH HAS A COMPLEMENTARY GRADIENT, AND IF THE EXON SEARCH OUT FOR A COMPLEMENTARY GRADIENT, HIGHER RECEPTOR SEARCH FOR LOWER LIGAND OTHER LOWER RECEPTOR FOR HIGHER LIGAND TO REACH A STEADY STATE ACTIVATION OF THE PROCESS THAT STOPPED EXON, ONE CAN IMAGINE YOU CAN HAVE A PROJECTION WHICH IS ARRANGED IN THE TECTUM. THIS PROJECTION, LOOKING AT EARLY DEVELOPMENT, THEY ARE NOT CORRECTLY SIZED. AND IT TURNS OUT THE ACTIVITY USE OF THE VISUAL SYSTEM CAN SHAPE THIS PRO JECTION FROM THE CELL TO THE TECTUM. NOW USING THIS, YOU CAN UNDERSTAND THIS PROCESS. FOR EXAMPLE, CELLS -- IN THIS CASE, TAD POLE, SEEING VISUAL STIMULUS ENVIRONMENT. THE VISUAL STIMULUS TEND TO BE CORRELATED IN SPACE AND TIME SEEING OBJECT AND SOMETHING FLYING FLEW THE -- THROUGH THE SPACE. THIS OBJECT INDIVIDUAL SPACE TRIGGER CO-RELATED FIRING OF NEIGHBORING GANG LA CELLS BECAUSE THEY HAD ARE FIRING CELLS PROJECTED TO THE NEIGHBORING GANGLION CELLS. SO NEIGHBORING GANGLION CELLS TEND TO FIRE BECAUSE OF CO-RELATED INPUT TOGETHER. SO IMAGINE THE CELLS THAT FIRE TOGETHER, THESE CELLS TEND TO WIRE TOGETHER AND THEN THEIR CONNECTION TO THE CENTRAL PROJECTION WOULD BE STABILIZED. WHILE GANGLION CELLS WHICH ARE FAR AWAY, THEY TEND NOT TO BE EXCITED BY AN OBJECT IN THE FIELD. THEY WILL NOT DEFINE AT THE SAME TIME. CAPTIONS RESUME LATER THE STRENGTH ARE ALL THE SAME. IT'S STARTING CONDITION. NOW IF I GIVE A STIMULUS THAT GIVES YOU A SEQUENTIAL EXCITATION OF THIS THROUGH THIS ENSEMBLE IN A SEQUENCE FROM LEFT TO RIGHT. THE RESULT WOULD BE THAT THE SYNAPTIC CONNECTION WOULD BE MODIFIED. SO WE WILL FIRE THE PRE, POST, FOR THE CONNECTION. THE FORWARD DIRECTION CONNECTION. THE SYNAPSE ARE SEEN PRESYNAPTIC ACTIVITY BEFORE POST SYNAPTIC ACTIVITY. SO THEY ALL BECOME STRENGTHENED. REVERSE SYNAPSE BECOME WEAKENED, ACCORDING TO STTP. WE ALL AGREE ABOUT THAT, GIVEN THE PROPER TIME OF THE EXCITATION. SO WE HAVE, AFTER TRAINING OF A UNIDIRECTION SEQUENTIAL ACTIVATION OF THIS ENSEMBLE OF NEURONS. WE CREATED ASYMMETRICAL ACTIVITY BASED ON SVTP (?) SO IF WE GIVE A PARTIAL STIMULUS, THAT IS JUST TO GIVE A INITIAL POINTED, BECAUSE OF STRENGTHENING OF THIS GROUP, YOU TEND TO FIRE THE NEXT GROUP OF NEURONS. SO, A PARTIAL STIMULUS CAN NOW EVOKE A SEQUENTIAL FIRING OF THE GROUP THAT ARE CONNECTED BY DOING THE TRAINING. SO, ONE CAN IMAGINE THAT THE MEMORY ARE STORED IN THE CONNECTIVITY AND RECALLED BY PARTIAL STIMULUS. SO CAN WE SHOW THE CORD CALL NEURON MIGHT BE USING INTERCORTICAL CONNECTION TO CARRY OUT THESE FUNCTIONS? SO THE EXPERIMENT WAS DONE BY TWO FORMER GRADUATE STUDENTS. USING RAT V1 AND MULTILATERAL RECORDING ON THE V1, WHICH MAPPING THE RECEPTOR FIELDS OF THIS VISUAL CORTEX. SO, HERE ARE THE MAPS THAT FOR 16 ELECTRODES. THEY ARE RESPONDING TO DIFFERENT REGIONS ON THE VISUAL FIELD AND THE MAP REGION CAN APPROXIMATE BY THESE CIRCLES. AND IF YOU RECORD FOR MORE OF THESE NEURONS, THIS 16 ELECTRODES, WILL YOU FIND THAT ACCORDING TO THE RECEPTIVE FEW POSITION, THEY ARE FIRING MORE OR LESS IN SEQUENCE. THERE ARE THOSE CLOSER TO THIS STUDY POINT TEND TO FIRE FIRST AND THEN FIRING IN THE SEQUENCE. WE CAN DEPICT THIS SEQUENTIAL FIRING BY CODING THE NUMBER OF SPIKES BY THE GREAT LEVELS OF THE CIRCLES. SO THIS IS WHAT WE WOULD GET DOING DURING CONDITIONING. VISUAL STIMULUS, A MOVING SPOT IS MOVING ACROSS THE FIELD AND THIS IS THE RECEPTIVE ELECTRODES. SO WHAT WE ARE SEEING SPEECHING THROUGH THE CONDITIONING. CONDITIONING THE FIRING IN A SEQUENCE MOON THE 16 GROUP OF NEURONS BEING RECORDED. SO, THIS CONDITION PRESUMABLY WOULD CREATE A MEMORY. THIS MEMORY WOULD BE INHERENT IN THE KICK ACTIVITIES AND THEN WE CAN RECORD THIS MEMORY AND RECALL THE SEQUENTIAL FIRING BY FIRING ONLY THE STARTING POINT, ONLY A FLUSH RATHER THAN A MOVING SPOT. THE FLESH ON THE END POINT SHOULD NOT CREATE A SEQUENTIAL FIRING EFFECTIVELY AS THE STARTING POINT BECAUSE THE CONNECTIVITY IS IN ONE DIRECTION. THIS IS WHAT WE ARE EXPECTING. SO THIS IS ONE EXAMPLE OF THE RESULT. AND WE STUDIED AND TESTED THE FLASH ON THE PRESUMED STARTING POINTED OF THE TRENDING POINT. THIS IS THE ROSTER OF 16 ELECTRODES. SO THERE IS CONTINUOUS ACTIVITY GOING ON. IF WE PLUSH AT A STARTING POINT OF THIS GROUP ENSEMBLE OF NEURONS, YOU WILL SEE THERE IS NO OTHER ACTIVITY THEY APPEARS TO BE REPPEDDERED. NOW IF WE GIVE YOU A SEQUENTIAL ACTIVATION WITH A MOVING SPOT, THEN THIS ACTIVITY STARTS TO BE MORE SEQUENTIAL. THE ONE THAT ACTIVATED -- THE EARLIER THEY GET THE SEQUENTIAL FIRING OF THE SET OF NEURONS. SO THIS IS A TRAINING. SO AFTER TRAINING, WE GO BACK TO TEST AND SEE IF WE CAN RECORD THIS ACTIVITY. AND THE ANSWER IS YES. 7 TRIALS IN THIS CASE, AT LEAST 4 OF THE 7 SHOW VERY NICE MAYBE 5 OUT OF 7 SHOW VERY NICE SEQUENTIAL SPIKING. THAT WAS TESTED AFTER A FEW MINUTES AFTER WE HAVE TREND CONDITION THE CORTEX OF THE SO WE CAN DO ANALYSIS WHICH I WILL NOT BOTHER YOU ABOUT AND THE CORRELATION OF THE SPIKING TO SHOW THE SEQUENTIAL SPIKING AND ANALYSIS USING THIS GRAPH SHOWING AFTER THE CONDITIONING, WE HAVE THIS ACTIVITY TOWARDS THE ACTIVITY SHOWING A SEQUENTIAL FIRING FOLLOWING THE SEEQUENCE. AND EITHER AWAKE ANIMAL OR ANESTHETIZE ANIMAL. THIS INCREASED SPIKE CAN BE RECALLED BY THE BEGINNING POINTS IN BOTH AWAKE AND ANESTHETIZED ANIMALS OR IN THE MIDDLE OF THE CONDITIONING PATHS. BUT NOT IN THE END. IF YOU FASHION END YOU DON'T SEE INCREASED CORRELATION. IF YOU FLASH THE WHOLE BAR RATHER THAN SEQUENTIAL ACTIVATION, SO, THE WHOLE BAR CONDITIONING PRODUCED NO SEQUENTIAL ACTIVATION, THEN AFTER THAT, YOU DON'T SEE THIS INCREASED CORRELATION. INCREASED SEQUENTIAL FIRING. SO ALL OF THIS SUGGESTS THAT IN DEED, IS THERE A MEMORY OF SEQUENTIAL FIRING CREATED BY A UNIDIRECTIONAL SEQUENTIAL ACTIVATION OF THE CORTICAL NEURONS. AND THIS FIRING LASTS FOR A COUPLE OF MINUTES. IT'S NOT VERY LONG. IN FACT, IN AWAKE ANIMALS, BY SIX MINUTES AFTER CONDITIONING, APPEAR TO BE NOT SIGNIFICANT OF THE SO A FEW MINUTES OF MEMORY OF A SEQUENTIAL INFORMATION PRESUMABLY TIMING DEPENDENT PLASTICITY. NOW THE QUESTION IS THE SPIKE TIMING OF THE CORTICAL NEURON SUFFICIENT AND NECESSARY FOR THE CORTEX TO LEARN THE SEQUENTIAL INFORMATION? SO WE CAN ALL TEST WITH THE NEW TOOLS OF OPT GENETICS TOOLS AND TEST WHETHER FIRING THE NEURON DIRECTLY RATHER THAN VISUAL STIMULUS, FIRING DIRECTLY SEQUENTIAL MANNER, CAN YOU IN R. IMPRINT SEQUENTIAL FIRING INTO THE CIRCUIT? THERE ARE TWO GRADUATE STUDENTS DOING THIS EXPERIMENTS USING. [ INDISCERNIBLE ] THROUGH CORTEX AND THEN PUTTING ELEC TOWED RECORD ALONG THE CORTEX BY EXPRESSING USING LIGHT ACTIVATION TO ACTEDIVATE NEURONS DIRECTLY IN A SEQUENCE. AND RIGHT AFTER THE CONDITIONING, YOU CAN TEST WHETHER THE -- YOU CAN RECALL THE SEQUENTIAL FIRING. NOW WITH THE OPT GENETIC STIMULATION, YOU CAN SEE THIS FIRING PSTH IS MUCH MORE REGULAR THAN VISUAL STIMULUS BECAUSE WE REALLY CONTROLLING THE GROUP OF NEURONS. YOU CAN SEE A NICE SEQUENTIAL FIRING OF THE CELLS RECORDED BY THESE ELECTRODES. THE ANSWER FOR THIS IS AFTER OR BEFORE THE CONDITIONING, TESTING AT A END POINTED YOU DO NOT SEE ANY SEQUENTIAL FIRING BUT WITH CONDITIONING AS I SHOW YOU BEFORE, THEN YOU TEST AGAIN YOU BEGIN DO SEE THIS SEQUENTIAL FIRING. SO THIS IS AN EXAMPLE. BEFORE THE CONDITIONING YOU LOOK AT THE GROUP OF ELECTRODES. THIS IS MULTIUNIT RECORDING. SEEMS TO BE RENDERED IN SEQUENCE. THEN CONDITIONING IMPOSES SEQUENCE. CONDITIONING BY LIGHT. GIVE YOU SEQUENCE AND THEN AFTER CONDITIONING, THE TEST WITH A FLASH IN THE BEGINNING. YOU START TO SEE SOME CLEAR SEQUENTIAL FIRING IN MANY CASES. SO, ACTIVATION OF NEURONS ITSELF IS SUFFICIENT TO IMPRINT A SEQUENTIAL INFORMATION THAT CAN BE RECALLED BY PARTIAL STIMULUS AT A STARTING POINT OF THIS SEQUENCE. THE CLEAR EXAMPLE OF SEQUENTIAL FIRING AFTER CONDITIONING FOR THE STARTING POINT FLASHES BUT NOT FOR ENDPOINTS FLASH. THE ANGEL FOR MANY CHOSE THIS END RESULT. SO THERE ARE STILL QUESTIONS TO BE ADDRESSED. FIRING CAN CREATE A SEQUENTIAL INFORMATION. IT'S THE SPIKING ITSELF REQUIRED NECESSARY FOR VISUALLY INDUCED MEMORY. YOU HAVE A VISUALLY INDUCED MOVING SPOT INDUCING SEQUENTIAL MEMORY IN THE BRAIN. IT REALLY DEPENDS ON THE CORTICAL NEURON FIRING. SO I CAN DO THAT EXPERIMENT NOW TO INHIBIT THE CORTICAL -- WE ARE ASSUMING THIS IS DUE TO LTP AND LTD. WE HAVE TO SHOW THAT IT IS VISUALLY CREATED, SEQUENTIAL FIRING CAN REALLY PROMOTE POTENTIATE LTP IN CREATING UNIDIRECTIONAL MANNER AND LTD AND OPPOSITE MANNER. THIS IS TO BE SHOWN. THERE ARE BRAIN STATE WE HAVE SHOWN EXPERIMENT CHI DIDN'T TELL YOU ABOUT, THE BRAIN STATE WEATHER THE CELL IS CORTICAL IN A AWAKE ALERT STATE OR DROWSY SLEEPY STATE. THERE ARE ABILITY TO RECORD THE MEMORY, SEQUENCE MEMORY IS DIFFERENT. THIS APPEARS TO BE EASIER TO RECORD IN MEMORY. BUT, WHETHER THE LEARNING OF THE SEQUENTIAL INFORMATION ALSO BECOMES A STATE IS NOT CLEAR. SO WE TEST RIGHT NOW. SO WE ALSO SHOW SEQUENTIAL ACTIVITY OF ACTIVATION OF A GROUP OF CORTICAL NEURONS. IF WE HAVE A NONACTIVATION FIXED SEQUENCE OF RENDERED ENSEMBLE, WOULD THOSE SEQUENCE FIRING STILL BE RECALLED AMONG THIS RANDOMLY SELECTED GROUP OF ENSEMBLE? THIS IS VERY IMPORTANT EXPERIMENT TO DO. WHILE FINALLY, WE ARE TALKING ABOUT A SHORTER MEMORY OF A FEW MINUTES WE REMEMBER SEQUENCING FORMATION AND THAT'S WHY I SHOW YOU THE MUSIC, THE SEQUENCE OF NOTES. THOSE ARE SOMEWHERE IN OUR BRAIN, SOMEWHERE, WE DON'T KNOW WHERE THEY ARE. ARE THEY IN THE CORTEX? OR SOMEWHERE ELSE? SEQUENCE INFORMATION CREATING THE CORTEX A TEMPORAL STORAGE OR LATER GET TRANSFERRED TO OTHER PLACES? THOSE ARE UNANSWERED QUESTIONS. SO I THINK I'M SLOWING PRESENTING MY STORY BUT I'LL TELL YOU ANOTHER STORY ABOUT HOW THE INTERVAL CAN BE CODED. I TALK ABOUT SEQUENCE. IN THIS STUDY, WE USE RANDOMLY CONNECTED HYPONEURON CULTURE RATHER THAN RANDOM CONNECTION ASSUMING IN VIVO. NOW THIS YOU CAN HAVE A GROUP OF HIPPOCAMPAL NEURON CULTURE IN THE DISH. EVERYBODY IS CONNECTED BASICALLY. AND SO IN THIS CASE, YOU CAN CREATE PLASTICITY AND CREATE LTP OR LTD BY FIRING THE CELL SEQUENTIALLY. OR FIRE THIS BEFORE THAT AND THEN THE CONNECTION FROM THIS CELL TO THAT CELL WILL BE STRENGTHENING. LTP AND LTD ARE DEMONSTRATED VERY NICELY, ASYMMETRIC DEPENDENT PLASTICITY IN THE CULTURAL SYSTEM. NOW WE ARE ASKED, CAN WE USE THIS SPIKE TIMING TO STORE THE MEMORY OF KIND INTERVAL? NOW WHAT DO WE MEAN BY TIME INTERVAL? HERE IS AN EXAMPLE OF HOW THIS CULTURE WILL WORK. HERE IS A CULTURE WITH THE RANDOMLY CONNECTED MEDIA THROUGH MANY OTHER CELLS. YOU HAVE A CELL BEING STIMULATED AND CELL RECORDED IN THE CULTURE. NOW BECAUSE IT GOES THROUGH MANY PATHWAYS TO REACH THE OTHER CELL, IF YOU EXCITE ONE CELL, THE RESPONSE YOU RECEIVE IN THE RECORDED CELL COULD BE MULTIPOLYSYNAPTIC GOING THROUGH MANY SYNAPSE. SO EACH OF THIS PEAK, IS INVERTED SYNAPTIC CURRENT, THE SYNAPTIC CURRENTS OF EACH PEAK REP SEPTEMBER A TRANSMISSION OF THE ACTION POTENTIAL SIGNAL FROM ONE PATHWAY THAT PRODUCES DELAY OF FIRST ONE ABOUT 20 MILLISECONDS TO REACH THE SECOND CELL. FOR THE SECOND PATHWAY, IT TAKES LONGER TO REACH THE RECORDED CELL. THE THIRD PATHWAY EVEN LONGER. SO BY LOOKING AT POLYSYNAPTIC REPRODUCIBLE POLYSYNAPTIC RESPONSE IN THE NEURON, YOU ACTUALLY ARE MONITORING PATHWAYS, SPECIFIC PATHWAYS IN THIS NETWORK. SO, THIS PATHWAY ARE VERY STABLE FOR A PERIOD WE CAN CREATE A WAY TO PRESENT THIS AMPLITUDE BY THE COLOR, WHITER COLOR OR RED COLORS USE HIGHER AMPLITUDE WITH TIME. THIS IS ONE TRACE HERE WILL BE ONE TRACE HERE. SO YOUR FIRST PEAK, SECOND PEAK, THIRD PEAK. AND WITH TIME, THIS PEAKS ARE STABLE. SO SAYING IN THE CULTURES, IT'S QUITE STABLE CONNECTIVITY. THE PATTERN IS CONNECTED. SO NOW WE ASK WHAT HAPPENED IF WE GIVE PATTERN INFORMATION INTO THIS WITH INTERVAL INFORMATION INTO THE SYSTEM? NOW CAN WE REPEATEDLY LEAVE IMPRINT IN THIS RANDOMLY CONNECTED CELL? WHAT IS THE SIMPLEST INTERVAL INFORMATION? [ INDISCERNIBLE ] WITH FIXED INTERVAL. SO THIS IS POST INTERVAL OF A FIXED DURATION AND REPEAT AGAIN AND AGAIN. SO THAT IS SIMPLEST INTERVAL INFORMATION WE CAN IMAGINE. SO NOW THAT IS FIT IN THIS. SIMPLE INTERVAL INFORMATION INTO THE NETWORK AND ASK WHAT HAPPENED TO THIS INFORMATION? HOW ARE THIS EXPERIMENT? THE SECOND AFTER THE INTERVAL, YOU GIVE ANOTHER PAIR A DEPOLARIZATION AND A SPIKE, IDENTICAL, RIGHT? SO BECAUSE OF THIS INTERVAL, BETWEEN THIS, YOU WOULD DETERMINE HOW THIS SIGNAL RECEIVE TARGET CELLS GOING TO INTERACT. IF YOU CHOOSE THE AIRPORT VAL RIGHT, THEN THE -- INTERVAL RIGHT, THEN THE SUBFLESH OR STIMULUS PRODUCED BY THE SECOND PULSE AND SPIKE CREATED BY THE FIRST PULSE. THEN YOU GET A POTENTIATION OF SYNAPSE AT THAT SITE. LTP. IF YOU CHANGE THE INTERVAL, MAKE IT LONGER INTERVAL, YOU MIGHT HAVE A SITUATION WHERE THE INPUT FALLS BEHIND THE SPIKE. YOU GET A SITUATION OF LTD. SO, BY DIFFERENT INTERVAL, WE WILL BE ABLE TO CREATE LTP OR LTD AT A VERY DIFFERENT SITE ALONG THESE NETWORKS SOMEWHERE WILL BE LTP AND SOMEWHERE WILL BE LTD DEPENDING ON THE INTERVAL OF THE PULSE. NOW CAN WE FIND THAT? CAN WE SEE THAT DIFFERENCE? HOW DO WE SEE THAT? WE CAN LOCATE THE POLYSYNAPTIC RESPONSE. HERE IS THE SIMPLEST ONE WHERE WE HAVE OR HAVE ONE ELECTRODES IN ONE CELL, STIMULATE ELECTRODES AND RECORD RESPONSE AFTER A FEEDBACK TO THAT CELL. SO, WE ELIMINATE THE RECORDING ELECTRODES. SIMPLEST CASE. SO WE HAVE RECORDING ARTIFACT FOLLOWED BY AFTER STIMULATION YOU GET A SYNAPTIC CURRENT RECORDING IN THE SAME CELL. THIS COMES AFTER A CIRCUIT THAT ACTIVATED CELL. THEN AFTER THIS, THIS IS A STABLE RECORDING, WE GIVE REPETITIVE PULSE INTO THE SYSTEM AND AFTER 50 PAIRS, 20 PARIS OF THE 50 MILLISECOND INTERVAL, WHAT HAPPENS IS NEW PEAKS APPEAR STIMULATING THE SAME CELL. WHAT DO THESE NEW PEAKS MEAN? NEW PATHWAY BEING ACTIVATED WITH DELAY OF LONGER DELAY OF TWO DIFFERENT PEAKS. THESE TWO PEAKS ARE THE LONGER DELAY REPRESENTING NEW PATHWAYS OF WHICH ARE LONGER THAT ACTIVATED. NOW WE HAVE ANOTHER EXAMPLE WHERE WE HAVE A POLYSYNAPTIC PEAK AFTER STIMULATION OF 30 MILLISECOND INTERVAL PAIRS, TWO PAIRS FOR 20 PAIRS. AFTER THIS INTERVAL, STIMULATION, THIS EARLY PAIR, SOME OF THE PEAKS DISAPPEAR. AND THE PATTERN CHANGES SOMETIMES NEW RESPONSE APPEARED AND SOMETIMES RESPONSE DISAPPEAR. POLYSYNAPTIC RESPONSE DISAPPEAR. SO PATHWAY TURNING ON AND OFF BY THIS DIFFERENT INTERVAL OF STIMULATION. SO, THIS IS WHAT IS REPRESENTED. YOU SEE THE SAME CELLS AND WE ARE USING ONE SINGLE CELL. YOU USE STIMULATION RECORDING. AND THERE ARE MANY PATHWAYS THAT FEEDBACK TO THE SAME CELL. IN THE BEGINNING, WITH THE 60 MILLISECOND INTERVAL PAIRS, 20 PAIRS PRODUCING NO PERMANENT EFFECT. WE HAVE THREE PIECE THAT SEEMS TO BE STABLE. TWO PIECES SEEM TO BE STABLE. NOW WHEN YOU CHANGE TO 60, SAME CELL, WE NOW HAVE TRAINING PARIS OF 40 MILLISECONDS OF 60 MILLISECONDS. IMMEDIATELY YOU HAVE NEW PATHWAY TURN ON. STABLE FOR AN HOUR. WE NOW CREATE A NEW PATHWAY WITHIN THE SYSTEM. SO THIS IS A CONSISTENT WITH DISTRIBUTED LTP AND LTD. CONSISTENT BUT DO DEMONSTRATE WHETHER IN PARTICULAR SITE THERE IS LTP AND LTD, WE ACTUALLY PERFORM REALLY TEDIOUS EXPERIMENT TO SHOW THAT IS ACTUALLY INDEED HAPPENING. SO THIS IS REPRODUCIBLE IT'S NOT AS RENDERED. BECAUSE HERE YOU SEE 100 MILLISECOND PRODUCE NO EFFECTS. 50 MILLISECONDS PRODUCE BIG CHANGE. AND 20 MILLISECOND PRODUCE FURTHER CHANGE. SO, IN SHORT, THE ANSWER FROM THIS IS THE CONCLUSION FROM THIS AREA OF STUDY IS THAT MEMORY OF INTERVAL UP TO 200 MILLISECONDS, CAN BE STORED IN THE NETWORK OF 20 NEURONS, CULTURE NEURONS. BY THE WAY WE ASSAYED IT IS TO LOOK AT A CHANGES IN THE PROBABILITY OF THESE POLYSYNAPTIC PEAKS THAT R. MODIFIED AFTER THAT PARTICULAR INTERVAL FOR A NUMBER OF PARIS. MANY EXCHANGES, MOST OF THEM ARE DEPENDING UPON AMDA RECEPTORS. IF YOU BLOCK WITH. [ INDISCERNIBLE ] VERY LITTLE CHANGE WILL BE OBSERVED. SO THE IDEA IS THAT IN TEMPORAL INFORMATION, CAN BE SPECIFICALLY DISTRIBUTED, LTP AND LTD BY SPIKE TIMING DEPENDENT PLASTICITY AT SYNAPTIC SITE. WHERE IS THAT WITHIN A NETWORK? EXACTLY WHERE? DEPENDS ON PATHWAY. SO, IS THIS A GOOD MODEL? REALISTIC MODEL? IN REAL LIFE, YOU EXCITE ONE NEURON, YOU DON'T FIRE THE NEXT NEURON. BECAUSE THE SYNAPTIC INPUT FROM ONE NEURON TO ANOTHER IS ALWAYS SUB FLESH. BUT YOU CAN FIRE A GROUP OF NEURONS AND FIRE A NEXT GROUP OF NEURONS. SO, IN THIS CULTURE MODEL, WE ARE SAYING THAT EACH CULTURE NEURON BECAUSE OF THE INTENSE CONNECTIVITY, THEY ARE REPRESENTATIVE A GROUP OF NEURONS. WHAT WE ARE SHOWING IS FIRING GROUPS OF NEURONS ACTIVATED EACH OTHER THROUGH DIFFERENT PATHWAYS AND THAT PATH ELEVENTH CAN BE USED TO STORE INFORMATION BASED ON THE DELAY, SYNAPTIC DELAY. IN THIS CASE, THE LONGEST WE CAN SHE CHANGES 200 INTERVAL CAUSES CHANGES IN THESE. SO, AT LEAST INTERVALS OF THIS SHORT TIME ACTUALLY CAN BE MEM RIDES. SO HOW ABOUT LONGER TIME INTERVAL? WHAT WOULD THAT HAPPEN? NOW ORIGINALLY POSTULATE. [ INDISCERNIBLE ] THE WAY THAT PERCEPTUAL INFORMATION IS ENGRAINED IN THE BRAIN IS TO CREATE A ACTIVITY AMONG THE GROUP OF NEURONS, CALLED CELL ASSEMBLE. THIS ACTIVITY CREATED BY THE PERCEPTUAL EXPERIENCE THAT WOULD LAST FOR A WHILE, WE CALORIE EVENTUATING ACTIVITY. AND THAT REVERBERATING ACTIVITY IS THE ACTIVITY THAT FIRES THE CELLS TOGETHER AND KICK THE LONG TERM. ANOTHER ACTIVITY WOULD BE THE MECHANISM TO STRENGTHEN THE CONNECTIVITY AMONG THE SET OF CELLS. NOW THIS IS PERHAPS POSTULATE. NOW OVER 60 YEARS PERIOD, PEOPLE HAVE LOOKED FOR THE REVERBATION. MOST PEOPLE SAID NO REVERBATION, HARD TO FIND IT. PERCEPTION, YOU CAN NOT SEE REVERBERATING ACTIVITY STILL GOING ON IN A CIRCUIT AFTER THE EXPERIENCE GONE. WE DECIDED A FEW YEARS AGO TO TEST THIS IN ZEBRAFISH WITH LARGE GROUP OF AS WELL AS IMAGING. HERE YOU CAN SEE MANY CELLS ANDIST AT THE AFTER EXPERIENCE THAT CAN BE MONITORED BY CALCIUM ACTIVITY. IT REFLECTS THE SPIKING, SPIKING ON NEURONS. EACH CALCIUM REFLECT THE NUMBER OF SPIKES THAT DIRECTLY PROPORTIONAL TO THE NUMBER OF SPIKES. INTEGRATED RESPONSE OF SPIKING. SO, IF YOU TAKE A EFFECT UM AND GIVE A STIMULUS TO THE -- TECH TUM -- GIVE A STIMULUS TO THE CEREBRA FISH, YOU SEE MANY ACTIVE. THIS IS A -- [ INDISCERNIBLE ] SOME NEURONS ARE NOT ACTIVE. EVERY SWEEP OF THE MOVING BAR ACROSS PRODUCE A TREND HERE. THEY ARE GOING VERY, VERY NICELY FOLLOWING THE SWEEPING OF THE VISUAL STIMULUS ACROSS THE RETINA. SO WOULD THIS VISUAL PERCEPTION OF REPETITIVE BARS ACROSS THE RETINA CREATIVITY IN THE ENSEMBLE OF CELLS THAT ARE LASTING LONGER THAN THE STIMULUS? WELL, HE FOUND SOME. HERE IS AN EXAMPLE. FIRST HE SHOWED THAT THIS ACTIVITY IN THE TECH TUM ARE HIGHLY SPECIFIC. THIS IS REPRESENTATIVE OF CALCIUM IMAGING. CALCIUM ACTIVITY REFLECTS 180 CELLS, VERY REPRODUCIBLE FOR LEFT MOVING BAR THAT CREATED A SET OF FIRING, THAT IS DIFFERENT FROM A RIGHT MOVING BOX. SOME OVERLAP BUT A LOT OF SPECIFIC TO THE DIRECTIONAL FEED OF THE BAR. THEY ARE REPRODUCIBLE AND REPRODUCED THE SAME FIRING. SO, DIFFERENT ENSEMBLE OF CELLS RESPONDING TO LEFT WORK PERCEPTION, RIGHT WORK PERCEPTION AND SOME USE FOR LEFT AND RIGHT. THAT IS VERY SIMPLE. SO THE QUESTION IS, WHAT HAPPENED? SO WHAT HE FOUND IS THAT AFTER THE PERCEPTION, AFTER THE MOVING AND CONDITIONING, IT STOPPED WITH CONDITIONING AND WATCHED THE CALCIUM ACTIVITY AND FOUND THAT THERE IS A REPEATED CORRELATED CALCIUM ACTIVITY AFTER CONDITION STIMULUS HAD STOPPED. HERE IS AGAIN REPETITIVE ACTIVITY. NOT TOO MANY CASES BUT THERE WILL BE A FEW REPEATS AFTER THE CONDITIONING. THE INTERESTING THING IS THAT THIS REPEAT IS EXACTLY THE RIGHT INTERVAL AS THE CONDITIONING RESPONSE. SO THE CONDITIONING OF 4 MILLISECONDS -- 4 SECOND INTERVAL -- AFTER TERMINATION OF CONDITIONING 4 SECOND, 8 SECOND YOU GET ACTIVITY. HE USES 6 SECOND INTERVALS AFTER CONDITIONING WAIT FOR 6 SECOND, 12 SECONDS, 18 SECONDS. YOU GOT CALCIUM ACTIVITY. CALCIUM ACTIVITY REAPPEAR WITH THE RIGHT INTERVAL AND CONDITION INTERVAL. AND 10 MILLISECONDS YOU HAVE A REPEAT AFTER 10, 20, IN ONE CASE 30 MILLISECOND. YOU GOT ACTIVITY. NOW THIS IS VERY STRIKING BECAUSE YOU THINK ABOUT THE FISH. ACTUALLY REMEMBERING THE BEATS OF THE STIMULUS THAT ARE -- ONCE EVERY 10 SECONDS YOU GET A STIMULUS. AND THE FISH ACTUALLY REMEMBER 10 SECONDS LATER THE BEAT WILL COME AND THEY SHOW THE CALCIUM ACTIVITY. SO, MY TIME IS ALMOST UP. - I'M GOING TO SHOW YOU A FUN MOVIE SHOWING HOW THIS EFFECTS THE BEHAVIOR OF THE FISH. THE BEHAVIOR CAN BE THE FISH ACTIVITY IMMOBILIZE ON A STAGE. WE CAN LOOK AT THE TAIL. THE TAIL MOVE. SO THEIR TAIL CAN SWING. THE HEAD IS THE AMOUNT OF CALCIUM. SO WE ASK WHEN THE CALCIUM ACTIVITY HAS OSCILLATIONS AFTER THE CONDITIONING, WHAT HAPPENED TO THE FISH BEHAVIOR? WELL, IN DOING THE CONDITIONING, EVERY FLASH PRODUCES A TAIL SWEEP. THE TAIL SWEEP IS A RESPONSE OF THE TAIL. YOU CAN MONITOR THE TAIL MOVEMENT. SO THE TAIL, 60-70% OF CASES, EVERY VISUAL STIMULUS CREATED A TAIL RESPONSE. BUT AFTER THE CONDITIONING, WAIT FOR TWO MORE INTERVAL, 6 AND HE COULD 12 SECOND, TWO MORE SWEEP EXACTLY AT THE TIME OF 6 SECOND INTERVAL. THE TAIL SWEEP AGAIN. THIS IS EXACTLY THE TIME IF YOU LOOK TAT IT TELLS THE IMAGING, THE WAVE OF CALCIUM REAPPEAR ON THE SAME GROUP OF CELLS THAT ARE BEING CONDITIONED. SO, THAT'S SHOW YOU THIS IS REALLY HOW GOOD THE TAD POLE IS MEMORIZING. I WANT TO SHOW YOU LAST 4 CONDITION STIMULUS. EVERY 6 SECOND. THE SONG -- I PUT IN THE SONG AND THE FLASH IS THE LIGHT, THAT'S THE STIMULUS. SONG IS FOR YOU TO RECOGNIZE THE TIME. YOU SEE THIS IS LAST CONDITION STIMULUS AND NO MORE STIMULUS. WAIT FOR 6 SECONDS. NO STIMULUS. 6 SECONDS. I BET THERE ARE -- THE FISH TIME IT BETTER THAN YOU WILL. KEEPING THE TIME. AND THIS TIME IS EXACTLY THE TIME WHEN THE CALCIUM OSCILLATION GOES UP IN THAT GROUP OF CELLS. SO, I THINK I HAVE TWO MINUTES LEFT FOR MY TIME. I REALLY WANT TO SHOW YOU A SET OF EXPERIMENT. THIS IS REALLY THE HIGH-LEVEL. WE TALK ABOUT THE PERCEPTION. THE PERCEPTION THAT MOST HIGH-LEVEL PERCEPTION IS THE SELF AWARENESS, CONSCIOUSNESS. WE SEE A MIRROR, MY FACE IN THE MIRROR, THAT IS ME. I'M AWARE OF MYSELF. THE ONLY HUMANS ARE SPECIES OF GREAT APES ARE KNOWN TO RECOGNIZE THEMSELVES IN THE MIRROR. BABY, HUMAN BABY TAKES TWO YEARS IN ORDER FOR THEM TO ACQUIRE THIS ABILITY TO SEE THEMSELVES IN THE MIRROR. SO THIS MAYBE ACQUIRED ABILITY. SOME PSYCHIATRIC PATIENTS OF AUTISTIC KIDS LOST ABILITY, LOST SELF AWARENESS, DOESN'T PAY ATTENTION TO THE MIRROR AND PROBABLY DOESN'T RECOGNIZE HIMSELF IN THE MIRROR. SO THE QUESTION IS, WHERE IS THE ORIGIN OF THIS SELF AWARENESS? MOST SPECIFICALLY, MIRROR IS SELF RECOGNITION AND AACQUIRED, CAN WE REINTRODUCE? REPAIR THE -- CURE THE IMPAIRMENT BY TREND? THIS IS THE MONKEY. MONKEY, RHESUS MONKEY CANNOT DO IT. THEY CANNOT RECOGNIZE THEMSELVES IN THE MIRROR. SO, SO THE HUMAN BRAIN, AT TWO YEARS OF AGE, THERE IS TREMENDOUS GROWTH OF NETWORK. DOING THIS IN GROWTH, MANY ABILITY ARE APPEARING. IS IT POSSIBLE THAT THE ACQUISITION OF THE SELF AWARENESS IS BECAUSE OF THIS THROUGH LEARNING. SO WE RECENTLY, THIS IS ALSO NONPUBLISHED. I THINK AGREE FOR ME TO TALK ABOUT THIS EVEN THOUGH IT'S UNPUBLISHED. THIS IS A FUN EXPERIMENT, YOU WILL SEE. WHAT WE DECIDED TO DO IS TO TRAIN MONKEY TO LEARN ASSOCIATION OF AN IMAGE IN THE MIRROR. THIS IS IMAGE IN THE MIRROR. THE MONKEY IS SITTING ON THE CHAIR. WE LEARN ASSOCIATION OF A VISUAL AND SENSORY ASSOCIATION FIRST BY THE SHINING OF THE LASER LIGHT AT THE HIGHER POWER THAT GIVES SOME FEELING, SOME PROBABLY TWINKLING FEELING. I FEEL A LITTLE BIT OF HEAT ON THE MONKEY. SO, WHEN MONKEYS SEE THIS IMAGE IN THE MIRROR, IT FEELS A SENSATION IN HIS OWN FACE. NOW THIS CAN BE VERY EASILY TRAINED. THE MONKEY, VERY QUICKLY, THEY WILL TOUCH THAT POINT. NOW PEE GIVE THE FOOD IN ORDER TO ENCOURAGE THEM TO TOUCH THE SPOT BECAUSE AFTERWARDS, WE ARE NOT USING HIGH-POWERED LASER. AFTER A FEW WEEKS OF TRAINING, YOU NOW USE A VERY LOW POWER LASER THAT PRODUCES NO FEELING IN HUMANS AND THEY WILL DO THIS. THEY WILL LOOK AT THE MIRROR AND THEN TOUCH THE SPOT. NOW BECAUSE THEY HAVE BEEN TRAINED TO DO THIS, THEY CAN RECEIVE FOOD. SO THAT IS WHY THE FOOD REWARD IS USEFUL IN THE BEGINNING. NOW BUT THE REAL STANDOUT TEST IN THE FIELD SINCE 40 YEARS AGO, DEMONSTRATING APES CAN HAVE CELL RECOGNITION -- SELF RECOGNITION IN THE MIRROR BUT NOT MONKEY, 40 YEARS AGO. THE STANDARD TEST TO MARK ON THE FACE OF THE MONKEY AND SEE WHERE THE MONEY LOOKING IN THE MIRROR AND TOUCH THAT DOT. NOW THIS IS CALLED A MARK TEST. THE MARK TEST IS THE MARK ON A MONKEYY FACE AND THE MONKEY WOULD TOUCH AFTER THE TRAINING. NOW NO FOOD. NOW THEY ARE NOT REWARDED. THEY JUST ROTATE THEIR FACE AT A DIFFERENT MARK, DIFFERENT COLOR. GREEN DYE ON THEIR FACE THEY SCRATCH AND LOOK. AND THIS IS THREE MORNINGIES LEARNED VERY, VERY WELL WITHOUT MIRRORS AND WITH MIRROR THEY TOUCHED. TOUCH THE SPOTS OR TOUCH THE DYE MARK. NOW THIS IS NOT GOOD ENOUGH. YOU HAVE TO SHOW THE SPONTANEOUS ACTIVITY, NOT ON THE CHIMP -- THEY SPONTANEOUS LOOK FOR THE MIRROR AND BRING IT TO BEHAVIOR, RIGHT? SO THIS IS FIRST WE DO DYE TEST IN THE WELL-TRAINED MONKEY. IN THE CAGE IS THERE A MIRROR. THEY LOOK AND THEY APPEAR TO LOOK AND ACTUALLY, FIND THREE MONKEY TRAINED. ONLY TWO ACTUALLY CAN DO THIS IN A CAGE. ONE MONKEY FAILED TO BE INTERESTED IN THE MIRROR IN THE CAGE, IN THE HOME CAGE. AND THE TIMING, THEY LOOK, THEY TIMELY TOUCH THE FACE, ALWAYS THE TIME THEY LOOK IN THE MIRROR. IT'S NOT COINCIDENCE. THEY CAN FOLLOW A SPOT. THIS IS SPOT THAT PRODUCE NO SENSATION. DIFFERENT COLORS AND FOLLOW THE SPOTS AND THEY VERY NICE RESPONSE IN AWL THREE MONKEYS. SO NOW FINAL TEST. ARE THEY LOOKING AT A MIRROR AND TOUCH FACE AS CONDITION RESPONSE? ANY FACE WITH A MONKEY FACE? WITH A SPOT ON THE FACE, THEY WILL TOUCH BECAUSE THEY ARE REALLY SEEING THAT THEMSELVES? WELL, ONE WAY IS THAT YOU PUT ANOTHER MONK NETHERE WITH THEIR FACE MARK ON THE FACE AND THE MONKEY LOOK AT EACH OTHER. THEY LOOK AT THE OTHER MONKEY WITH THE FACE MASK AND TOUCH THE OTHER MONKEY TOUCH THEMSELVES. SO COHORTS WITH THE NAIVE MONKEY WITH THE FACE MARK. THIS IS THE ONE EXPERIMENT. SO NAIVE MONKEY IS THE YELLOW COLLAR. SO THE NAIVE MONKEY HAS A MARK ON THE FACE AND THE TRAINED MONKEYS DOESN'T TOUCH HIS OWN FACE, HE TOUCH THE FACE OF THE NAIVE MONKEY. AND WHEN HE LOOKS ON HIS OWN, HE WILL TOUCH ON HIS OWN. THE TRAINED MONKEY ALWAYS TOUCH HIS OWN FACE. NOW FINALLY, THE TEST IS A BETTER TEST. NOW BEFORE I SAY THAT, SO WE HAVE ANOTHER MONKEY. THIS IS CALLED THE GLASS MIRROR TEST. WE ULTIMATELY THE GLASS TRANSPARENT GLASS IN THE MIRROR WITH TWO MONKEYS. BOTH MARK SAME POSITION CORRESPONDING POSITION. SO THE MONKEY, TRAINED MORNINGIES LOOKING THROUGH A GLASS, ANOTHER MONKEY WITH THE SAME MARK. WHAT WILL HAPPEN? DOES HE TOUCH HIS OWN FACE OR HAVE SOCIAL BEHAVIOR? THE ANSWER IS THEY HAVE SOCIAL INTERACTION. THEY NEVER TOUCH HIS OWN FACE. BUT THEN YOU HAVE MIRROR. HALF OF THE TIME WITH GLASS, HALFTIME WITH MIRROR, BACK AND FORTH. WHEN THE MIRROR WAS PRESENTED, THE MONKEY WILL TOUCH HIS OWN FACE. THIS IS THE MIRROR GLASS TEST. WITH THE GLASS WALL, THE ONLY TIME THEY APPEAR, IS THERE A SOCIAL BEHAVIOR THROUGH THE GLASS WITHOUT TOUCHING. NOW THE MIRROR IS IN. SO IT APPEARS THAT THIS WORKED. THAT THE GLASS MIRROR, HE SEEMED TO RECOGNIZE HIMSELF. SO FINALLY NOT ON THE FACE BUT IN ANOTHER AREA, THEY HAVE NEVER BEEN TRAINED, LIKE EAR, THEY WOULD LOOK AT THIS TRAINED MONKEY WOULD LOOK AND REACH. THEY WOULD LOOK AT THEMSELVES IN PLACES WHERE THEY ARE CURIOUS ABOUT. THE NAIVE MONKEY -- [ LAUGHS ] OKAY, IMPLICATIONS, RHESUS MONKEY LEARNED MIRROR SELF RECOGNITION. HUMAN BABIES, THEY ACQUIRE THE 80 VIA LEARNING DURING THE FIRST TWO YEARS. IMPAIRMENT OF SELF AWARENESS MAY BE TREATED WITH TRAINING. THESE ARE PEOPLE WHO CONTRIBUTE TO THE WORK. I MENTIONED MOST OF THEM. BOTH IN UCSD AND BERKELEY AND NOW IN SHANGHAI. THANK YOU VERY MUCH. [ APPLAUSE ]