>> THANK YOU ALL FOR BEING HERE TODAY. I WANT TO INTRODUCE TODAY'S SEMINAR SPEAKER, DR. DON KATZ, ASSOCIATE PROFESSOR, BRANDEIS UNIVERSITY IN THE DEPARTMENT OF PSYCHOLOGY. HE'S ALSO A MEMBER OF THE VOLEN NATIONAL CENTER FOR COMPLEX SYSTEMS, WHICH IS REALLY FORMED TO STUDY THE BRAIN AND INTELLIGENCE. DON GOT HIS PH.D. AT INDIANA UNIVERSITY IN PSYCHOLOGY AND NEUROSCIENCE, STUDYING ACTIVITY IN VARIOUS PARTS OF THE BRAIN LINKED TO ASSOCIATIVE LEARNING, IN PARTICULAR, EYE BLINK CONDITIONING AND CEREBELLAR CORTEX, I JUST LEARNED HE WORKED WITH RABBITS IN THIS. THIS INTEGRATIVE APPROACH THAT HE TOOK IN TRYING TO LINK THE FUNCTION OF DIFFERENT PARTS OF THE BRAIN TOWARDS LEARNING WAS FURTHER SORT OF DEVELOPED IN HIS POSTDOC AT DUKE UNIVERSITY. IN MIGUEL'S LAB, DON WORKED WITH SYD SIMON TO EXPLORE SENSORY INTEGRATION IN THE GUSTATORY CORTEX, AND USING MULTIELECTRODE ARRAYS PRIMARILY. HE EXPANDED ON THIS WORK THEN IN HIS OWN LAB AT BRAN DICE,DEIS, ALSO TRYING TO UNDERSTAND GUSTATORY CODING IN THE CORTEX AND HOW THESE SIGNALS ARE THEN AFFECTED AND FUNCTION IN LEARNING AND MEMORY. SO I THINK WE'LL BE HEARING ABOUT THIS WORK TODAY, JUST WANTED TO WELCOME HIM HERE AND HOPE YOU ALL JOIN ME IN WELCOMING DON KATZ. [APPLAUSE] >> THANK YOU VERY MUCH. IT'S GREAT TO BE HERE. I'LL JUST DIVE RIGHT IN. I'M GOING TO ACTUALLY TALK ABOUT TWO RELATED PROJECTS, IF I HAVE TIME. FOR STARTERS, I WANT TO EXHIBIT DUES YOU TO INTRODUCE YOU TO THE TASTE SYSTEM WHICH IS RIDICULOUSLY SIMPLE AND I'M GOING TO GIVE AN EVEN MORE SIMPLISTIC VIEW OF IT COMPARED TO SYSTEMS LIKE THE SMA TOE SENSORY, AUDITORY, VISUAL SYSTEM, THE TASTE SYSTEM IS FAIRLY SIMPLE BUT IT DOESN'T MEAN IT'S EASY TO UNDERSTAND. HERE IS, AGAIN, A RIDICULOUSLY SIMPLISTIC IMAGE OF THE RODENT TASTE SYSTEM. FROM THE TASTE BUDS, YOU HAVE THREE SEPARATE CRANIAL NERVES ALL CARRYING TASTE INFORMATION TO THE NUCLEUS OF THE SOLITARY TRACT. THEN IF YOU GO NORTH FROM THAT, YOU SEE THAT THERE IS THE CLASSIC PATHWAY LEADING YOU UP TO PRIMARY GUSTATORY CORTEX, WHICH I'M GOING TO CALL G.C. FOR THE REST OF THE TALK. BUT YOU'RE GOING TO ALSO SEE IN THIS PICTURE THAT AT THE LEVEL OF THE BRAINSTEM, THIS IS THE SECOND BRAINSTEM RELAY, THIS IS THE PONS, THERE IS AN ADDITIONAL PATHWAY THAT IS SOMETIMES CALLED THE LIMBIC PATHWAY OR THE FOREBRAIN -- OR THE SUBCORTICAL FOREBRAIN PATHWAY, WHICH TAKES YOU TO THE LIMBIC SYSTEM. NEURONS FROM THE PBN SYNAPSE ON A NUMBER OF DIFFERENT PLACES IN THE BRAIN, INCLUDING THE LATERAL HYPOTHALAMUS, THE AMYGDALA, THE BST, AND AT THESE PATHWAY, THEN ALSO CONVERGE ON CORTEX. YOU'LL ALSO NOTICE THAT THESE PATHWAYS FROM THESE STRUCTURES TO CORTEX ARE RECIPROCAL, SO THE CORTEX IS ALSO COMMUNICATING BACK DOWN TO EACH OF THESE REGIONS, AND SO YOU END UP WITH A FAIRLY COMPLEX PATTERNING. IF YOU ARE A G.C. NEURON, AND YOU ARE RECORDING WHAT HAPPENS AFTER THE TASTE HITS THE TONGUE, THERE IS A LOT OF ACTION THAT'S HAPPENING IN THE SYSTEM CONVERGING UPON G.C., THEN GOING BACK DOWN, THEN COMING BACK UP. YOU WOULD EXPECT IN REALTIME TO SEE SOME FAIRLY FANCY EFFECTS, AND IN FACT, THIS HAS A RELATED -- A SET OF RELATED IMPLICATIONS. IF YOU ARE RECORDING FROM A NEURON IN G.C. OR GOD FORBID A SET OF NEURONS SIMULTANEOUSLY IN G.C., AND YOU ARE RECORDING WHEN A TASTE HITS THE TONGUE, YOU WOULD EXPECT ACTIVITY TO COME UP THIS PATHWAY. YOU'D ALSO EXPECT THE ACTIVITY TO GO TO THIS PATHWAY AND THEN COME TO THE CORTEX, AND THEN YOU WOULD EXPECT ACTIVITY TO GO BACK DOWN AND THEN TO COME BACK UP, SO YOU WOULD EXPECT DYNAMICS IN THE RESPONSE. WOULD YOU EXPECT THAT IF YOU'RE RECORDING FROM NEURONS IN G.C., YOU ARE NOT SIMPLY GOING TO GET AN ON OR NOT ON RESPONSE, YOU'RE NOT EVEN GOING TO JUST GET ON TO A CERTAIN LEVEL. YOU WOULD EXPECT AS YOU RECORD THROUGH TIME TO SEE A PATTERN, SEE DYNAMICS. FURTHERMORE, YOU WOULD EXPECT IF YOU ASK ANY COMPUTATIONALLIST, YOU WOULD EXPECT A SYSTEM SET UP LIKE THIS, YOU ARE GOING TO GET NEURONS COHERING INTO FUNCTIONAL UNITS, YOU WOULD EXPECT ENSEMBLE CODING, AS YOU RECORD FROM A GROUP OF NEURONS AND LOOK AT THEM TOGETHER, THERE'S GOING TO BE RELATIONSHIPS IN THEIR FIRING CAUSED BY THIS SORT OF CIRCUITRY. FINALLY, IF ANY OF THIS IS REAL, IS USEFUL, YOU WOULD EXPECT THIS ACTIVITY, THESE DYNAMICS AND THIS ENSEMBLE CODING TO BE LINKED TO BEHAVIOR. WE HEAR -- IF YOU TRAVEL IN THE CIRCLES I TRAVEL IN, YOU HEAR A LOT OF TALKS ABOUT DYNAMIC ENSEMBLE CODING AND IT ALL ENDS UP MEANING VERY LITTLE UNLESS YOU CAN RELATE THAT DIRECTLY TO BEHAVIOR. AND SO IT'S OF PARTICULAR IMPORTANCE WHEN WE'RE STUDYING GUSTATORY CORTEX, IN ADDITION TO ALL THESE CONNECTIONS, THE STUFF IN THE TASTE BUDS AND FROM THE DESCENDING CONNECTIONS FROM THE GUSTATORY CORTEX, CONVERGE UPON LOCAL BRAINSTEM CONNECTIONS WHICH ACTUALLY FUNCTION AS CENTRAL PATTERN GENERATOR FOR MULTI- -- MULTIFUNCTION CENTRAL PATTERN GENERATOR FOR THE MOUTH MOVEMENTS THAT THEN CAUSE AN ANIMAL TO EITHER SWALLOW OR EXPEL A FLUID ON THE TONGUE. SO YOU HAVE THIS DIRECT INPUT FROM THE TASTE BUDS TO THIS, AND YOU HAVE A MASS OF DESCENDING INPUT FROM THE CORTEX, WHICH AGAIN SHOULD HIGHLIGHT THE FACT THAT THIS ACTIVITY UP HERE SHOULD, IF IT MEANS ANYTHING, BE PRIME TO HAVE AN IMPACT ON THE CPGs. SO THAT'S WHAT I'M GOING TO TALK TO YOU FOR AT LEAST MOST OF TODAY, AND TO START WITH, I'M GOING TO DO SOMETHING THAT ALWAYS DEPRESSES ME A LITTLE BIT, I'M GOING TO TAKE MY FIVE-YEAR POSTDOC AND DUKE AND REDUCE IT TO A SINGLE SLIDE. WHAT WE SAW WHEN I WAS AT DUKE AND WE WERE RECORDING FROM THE GUSTATORY CORTEX, WE SAW THAT RESPONSES TO TASTES IN GUSTATORY CORTICAL NEURONS ARE NOT SIMPLE, THEY ARE, IN FACT, COMPLEX. SO I'M GOING TO EXPLAIN THESE COMPLEXITIES TO YOU A LITTLE BIT, THIS IS A STANDARD PIR EE STIM EU LUS TIME, THERE'S ACTUALLY A SET OF THEM, PERISTIMULUS, MEANING AROUND THE TIME OF STIMULUS DELIVERY, TIME, HISTOGRAM OF FIRING. AND I'VE OVERLANE THE RESPONSES TO A WHOLE SET OF TASTES IN A SINGLE EXAMPLE GUSTATORY CORTICAL NEURON JUST SO I CAN TELL YOU IN THIS REPRESENTATIVE NEURON THE KIND OF THINGS WE SEE AND WHAT YOU CAN SEE IF YOU LOOK AT THIS IS THAT THE RESPONSE OF THIS NEURON HAS ESSENTIALLY THREE PHASES. THE TASTE HITS THE TONGUE AND IMMEDIATELY THERE'S A BURST OF ACTION POTENTIALS, A SUDDEN INCREASE IN FIRING RATE, BY THE WAY, OTHER NEURONS MAY HAVE A SUDDEN DECREASE IN FIRING RATE, BUT YOU CAN SEE THAT IT'S PRETTY MUCH IDENTICAL FOR EVERY TASTE. AND FURTHEMORE FOR EVERY FLUID. IF I PUT WATER ON THE TONGUE OF THIS NEURON, YOU GET THAT SAME BURST OF ACTION POTENTIALS TELLS US NOTHING ABOUT WHAT THE STIMULUS IS. WE REFER TO THAT AS THE DETECTION RESPONSE, BECAUSE WE AS SCIENTISTS CAN LOOK AT THIS NEURON AND TELL THAT SOMETHING HAS HIT THE TONGUE. AND THAT'S ALL WE CAN TELL. WE'RE NOT SAYING HERE THAT THE ANIMAL USES THIS, ALTHOUGH A LOT OF MY COLLEAGUES HAVE SUGGESTED TO ME THAT THIS IS AN ALERTING SIGNAL FOR THE ANIMAL, WE DON'T KNOW. BUT WHAT YOU CAN SEE IS THAT WITHIN A COUPLE HUNDRED MILLISECONDS, THAT RESPONSE SHIFTS, AND NOW BY THE TIME YOU'RE TWO, 250 MILLISECONDS IN, THIS THE RESPONSE OF THIS WILL NEURON DISTINGUISHES BETWEEN AT LEAST A SUBSET OF THE TASTES. SO NOW YOU'VE HAD A KNEW PHASE NEW PHASE WHERE THE RESPONSE IS TASTE-SPECIFIC, SO WE REFER TO THIS AS THE IDENTIFICATION RESPONSE. WE AS SCIENTISTS CAN LOOK AT THIS ACTIVITY, DO SOME SIMPLE ANALYSES OF IT AND TELL YOU WHAT THE TASTE IS ON THE TONGUE. MIND YOU, THE RESPONSE IN THIS EPIC,THIS PERIOD IS VERY CELL-SPECIFIC. ONE CELL MIGHT RESPOND DIFFERENTLY TO EVERY TASTE, ONE MIGHT RESPOND ONLY TO ONE TASTE, ONE CELL MIGHT RESPOND SIMILARLY TO A COUPLE TASTES AND DIFFERENTLY TO OTHER TASTES, VERY SPECIFIC, BUT THE IMPORTANT THING IS THAT THERE IS THEN ANOTHER SHIFT IN FIRING ATION YOU FIRING INTO A WHOLE DIFFERENT PHASE OF RESPONDING IN WHICH THE RESPONSE IS VERY RELIABLE FROM CELL-TO-CELL. YOU CAN SEE THAT THE STRONGEST RESPONSE DURING THIS LATE PERIOD IS QUININE, WHICH IS A VERY NASTY BITTER TASTE, ALTHOUGH IT'S DELICIOUS WITH GIN, AND THAT IS WHAT THIS NEURON RESPONDS MOST STRONGLY TO, WHEREAS THIS NEURON RESPONDS MOST WEEKLY TO SUCROSE, WHICH IS THE MOST PALATABLE, MOST POSITIVE TASTE, AND IN THIS LATER PERIOD THAT COMES ON BETWEEN HALF A SECOND AND A SECOND AFTER THE STIMULUS HITS THE TONGUE, YOU EITHER SEE THIS KIND OF RESPONSE OR YOU SEE THE REVERSE, THE STRONGEST RESPONSE TO SUCROSE AND THE WEAKEST RESPONSE TO QUININE, THIS IS A PALATABILITY RESPONSE IN WHICH WE AS INVESTIGATORS CAN TELL YOU WHETHER THE RAT WILL BE THINKING, SHOULD I EAT THIS? WHETHER I WILL BE THINKING I WANT THIS OR I WANT IT OUT OF MY MOUTH. SO THIS IS SOMETHING THAT TURNED OUT TO BE RELIABLE ACROSS GC POPULATIONS, AND I KNOW THAT FOR SOME OF YOU, THIS IS SOMETHING QUITE NEW AND NOT UNEXPECTED. SO I'LL TELL YOU A COUPLE THINGS. FIRST OF ALL, WE CAN ANALYZE THIS VERY SIMPLY BY DOING A CORRELATION COEFFICIENT WITH PALATE FOR THE FIRING AT ANY MOMENT IN TIME THIS NEURON OF THE DIFFERENT TASTE AND THE KNOWN PALATABILITY OF THE TASTES, AND WHEN YOU DO THAT, YOU SEE THAT DURING THE MIDDLE PERIOD, THE IDENTIFICATION PERIOD, EVEN THOUGH THIS IS STRONGLY TASTE-SPECIFIC, IT IS NOT WILL PALATABILITY CORRELATED AND THEN THIS CORRELATION RISES ACROSS THE CHANGE FROM THIS PHASE TO THIS PHASE, UNTIL IT GETS VERY HIGH AND AT THIS POINT, THE NEURON'S RESPONSE IS HIGHLY CORRELATED WITH WHETHER THE ANIMAL SHOULD CONSUME IT OR NOT. AGAIN, A LOT OF THESE THINGS ARE NEW TO A LOT OF PEOPLE SO I WOULD LIKE TO BRIEFLY POINT OUT, I KNOW THIS IS KIND OF A MACHISMO SLIDE, THIS IS ABOUT 15 STUDIES THAT WE'VE DONE AT BRANDIES BRANEIS, OR THAT BY CHALLENGING THE ANIMAL'S ABILITY TO IDENTIFY THE NEURON, WE CHANGE ONLY THE IDENTITY PHASE OF THE RESPONSE, AND SHOWING RELATED AND COMPLEMENTARY DYNAMICS IN OTHER BRAIN AREAS SO MUCH OF WHAT WE'VE DONE AT BRANDEIS HAS BEEN TIME SPENT JUSTIFYING AND VALIDATING THE CHARACTERIZATION THAT I JUST SHOWED YOU, IT IS, IN FACT, THE CASE THAT THESE RESPONSES HAVE THREE EPICS AND THE EPICS AREN'T JUST PHENOMENAL LOGICAL. THEY ARE RELATED TO THE PROCESSING THAT WE'VE DESCRIBED, AND SO FROM A PSYCHOLOGICAL STANDPOINT, YOU CAN THINK OF IT AS YOU LOOK AT THESE NEURONS, YOU CAN SEE THE ANIMAL GET THE TASTE ON ITS TONGUE, SAY SOMETHING IS ON MY TONGUE, A MOMENT LATER, HEY, IT'S QUININE, A MOMENT LATER, I'VE GOT TO GET THAT OUT. BUT THAT'S NOT WHAT I WANT TO TAU TO YOU TODAY, I WANT TO MOVE ON FROM THERE, BECAUSE I WANT TO TELL YOU MOSTLY ABOUT WHAT WE GOT WRONG IN THE CHARACTERIZATION YOU JUST SHOWED YOU. CHARACTERIZATION I JUST SHOWED YOU SHOWED PALATABILITY INFORMATION RAMPING UP ACROSS A CERTAIN TIME PERIOD. THE CORRELATION WITH PALATABILITY WAS PRETTY MUCH -- IS PRETTY MUCH ZERO, AT ABOUT HALF A SECOND IN, EVEN THOUGH THE NEURON IS RESPONDING TASTE-SPECIFIC, AND THEN IT CLIMBS ACROSS A HALF A SECOND OR EVEN MORE TO BECOME VERY HIGH. WE WERE VERY EXCITED WHEN WE SAW THIS. BECAUSE IT CONFORMS WITH WORK IN THE NEUROBIOLOGY OF DECISION-MAKING ON HOW A DECISION VARIABLE RAMPS UP ACROSS THE TIME OF THE ANIMALS MAKING THE DECISION, AND WHEN IT GETS TO A CERTAIN THRESHOLD, THE ANIMAL EMITS A DECISION, THAT RAMP GOT NICE AND HIGH AT JUST ABOUT THE TIME THE ANIMAL MAKES A RESPONSE. UNDER MOST CIRCUMSTANCES, THE ANIMAL WILL MAKE A BEHAVIOR EITHER EJECTING THE FLUID FROM THE MOUTH OR SWALLOWING IT A LITTLE AFTER A SECOND HAS GONE BY. SO WE'RE VERY EXCITED ABOUT THAT. THERE'S ONLY ONE PROBLEM. IT TURNED OUT THAT THAT CHARACTERIZATION WAS INCORRECT AND LET ME EXPLAIN WHY. SO HERE IS THE CHARACTERIZATION THAT I'VE ALREADY GIVEN YOU. IN FACT, YOU'LL NOTICE I HAVE ONE COLOR BLEEDING INTO THE NEXT TO SHOW YOU THAT IT SEEMED TO BE THE CASE THAT THEY CHANGED SLOWLY FROM ONE OH TO THE OTHER, AND NOW I'M GOING TO SHOW YOU WHAT SINGLE TRIALS ACTUALLY LOOK LIKE. HERE IS A SUNK SINGLE TRY OF A SUCROSE DELIVERY IN AN ANIMAL WHERE WE'RE RECORDING FROM A SET OF NINE NEURONS SIMULTANEOUSLY. SO ALL THE POPULATION CODING STUFF I'M GOING TO TALK TO YOU ABOUT IS SPECIFICALLY LIMITED TO NEURONS THAT ARE BEING SIMULTANEOUSLY RECORDED PAUSE THOSE ARE THE NEURONS THAT ARE WORKING TOGETHER, AND SO THIS IS THE SINGLE TRIAL, I WANT YOU TO PARTICULARLY -- OH, SO EACH OF THESE HASH MARKS IS AN ACTION POTENTIAL EMITTED BY THAT NEURON, AND WHAT I'D LIKE TO FOCUS YOU IN ON MOSTLY ARE THESE THREE NEURONS THAT MY POSTDOC HELPFULLY COLORED IN AS SORT OF A BURNT UM BER, AND WHAT YOU CAN NOTICE IS THAT THERE IS A TRANSITION BETWEEN THE IDENTIFICATION OF THE PALATABILITY PHASE BUT THAT IT'S NOT RAMP LIKE AT ALL. I'M GOING TO GIVE YOU A LITTLE HELPFUL LINE, HAPPENS RIGHT THERE. ON THIS SIDE OF THE LINE, NEURON 9 IS PRETTY MUCH DOING NOTHING. AND THEN ON THE OTHER SIDE OF THE LINE, THE NEURON HAS BASICALLY JUMPED INTO A STATE OF RELATIVELY HIGH FIRING RATE. AT ABOUT THE SAME TIME, NEURONS 2 AND 3 GO FROM FIRING QUITE A BIT TO FIRING VERY LITTLE. NOW THIS IS A LITTLE LESS CLEAR BUT HANG ON, I'M GOING TO SHOW YOU MORE. THIS SUGGESTED SOMETHING -- IT DIDN'T LOOK RIGHT TO US. SO WE WENT AND LOOKED AT THE VERY NEXT TRIAL AND WHAT WE SAW WAS THE EXACT SAME THING WITH ONE DIFFERENCE. THE TIME POINT AT WHICH THAT TRANSITION OCCURRED WAS DIFFERENT IN THAT SECOND TRIAL. YOU CAN SEE THAT NEURON 9 WENT FROM FIRING NOTHING OR ALMOST NOTHING TO FIRING HIGH. NEURONS 2 AND 3 WENT FROM FIRING HIGH TO FIRING LOW. IT DIDN'T SLOWLY EMERGE. IT HAPPENED ALL OF A SUDDEN. HERE'S THE VERY NEXT TRIAL. SAME PHENOMENON, DIFFERENT TIME POINT, IT DIDN'T LOOK LIKE THIS PHASE, THIS TRANSITION BETWEEN IDENTIFICATION PALATABILITY AND DECISION WAS HAPPENING GRADUALLY. IT LOOKED LIKE IT WAS HAPPENING VERY SUDDENLY, AND WHAT WE HAD, IN FACT, WAS A SET OF NEURONS THAT WENT THROUGH A COUPLE OF DISTINCT STATES. THE STATES COULD BE DESCRIBED IN TERMS OF THE FIRING RATE OF EACH NEURON AND THERE WAS A SUDDEN TRANSITION FROM ONE STATE TO THE OTHER. AND SO THIS, OF COURSE, HAS JUST BEEN ME SHOWING YOU RAW DATA. ACTUALLY UNLIKE A LOT OF MY COLLEAGUES, I'M NOT OF THE OPINION THAT RAW DATA IS REALLY SUPER USEFUL, PARTICULARLY ELECTROPHYSIOLOGY. YOU TELL ME WHAT YOU WANT THE GUSTATORY CORTEX NEURON TO DO, I WILL FIND YOU AN EXAMPLE NEURON THAT DOES IT, SO WHAT WE ACTUALLY WANTED TO DO IS ANALYZE THIS, AND SO AT THE RISK OF MAKING MY TALK VERY METHODSY, I'M GOING TO TELL YOU A LITTLE BIT ABOUT THE ANALYSIS WE DID, CALLED HIDDEN MARK OFF MODELING OR HMM. IT TAKES A SET OF INPUTS THAT IS MULTIVARIATE, AND BY THE WAY, UNTIL VERY RECENTLY, WHEN YOU TALKED TO THE AIRLINES AND YOU WOULD TALK TO A COMPUTER THAT TRIED TO INTERPRET YOUR VOICE, YOU WERE ESSENTIALLY TALKING TO AN HMM THAT TOOK THE MULTIPLE FREQUENCY RANGES OF YOUR VOICE AND' TEMPTED TO DESCRIBE THEM IN TERMS OF A SET OF STATES WITH TRANSITIONS BETWEEN THE STATES. JUST LIKE WE THINK WE SEE, AND SO THAT'S AN -- IN THE CASE OF VOICE RECOGNITION, THE STATES ARE SYLLABLES, IN THE CASE OF WHAT WE'RE DOING HERE, WE'RE SUGGESTING THAT IT TAKES THE INPUT, THE SETS OF NEURONS AND SAYS -- DEFINES THEM IN TERMS OF FIRING RATE STATES WITH CERTAIN TRAN SUGGESTIONS BETWEEN THEM. YOU CAN TAKE THE OUTPUT OF THIS ANALYSIS AND READ IT LIKE THIS, THIS IS WHAT THE OUTPUT LOOKS LIKE IN THE WAY WE SHOW IT. YOU HAVE ALONG THE X AXIS TIME, BUT WHAT'S IN THE Y AXIS IS ACCORDING TO THE ANALYSIS, THE PROBABILITY THAT THE WHOLE SET OF NEURONS IS IN A PARTICULAR STATE. AND WHAT WE WOULD HOPE WOULD BE THE CASE IN THIS EXAMPLE, IT'S THE KAI WHAT WE WOULD HOPE WOULD BE THE CASE ACCORDING TO WHAT I'VE JUST SHOWN YOU IS THAT YOU WOULD GO FROM HAVING IT BE HIGH PROBABILITY IN A PARTICULAR STATE TO SUDDENLY BEING HIGH PROBABILITY IN A DIFFERENT STATE TO SUDDENLY BEING HIGH PROBABILITY IN A DIFFERENT STATE, ET CETERA, ET CETERA. THAT'S WHAT THE RAW TAI DATA THAT I JUST SHOWED YOU SUGGESTED TO US MIGHT BE TRUE, AND BY THE WAY, SO WE HAVE DIFFERENT COLORS REPRESENTING THE DIFFERENT STATES. THE HORIZONTAL DASHED LINE IS JUST AN ARBITRARY LINE, WE SAID AT 75% OR 80% -- PROBABILITY OF .75 OR .8, WE'RE GOING TO CALL THAT STATE HIGHLY LIKELY AND COLOR IT IN IN A PARTICULAR COLOR. THE TALK WOULD BE VERY SHORT, IF THAT'S NOT WHAT WE SAW, BUT IT IS, IN FACT, WHAT WE SAW. HERE IS A SINGLE TRIAL, AGAIN, OF SUCROSE, AND YOU CAN SEE -- WHAT I'VE DONE IS I'VE OVERLAIN THE FIRING ON TOP OF THE HMM SOLUTION. WHAT YOU'RE GOING TO SEE IS IT DOES, IN FACT, LOOK LIKE THE SET OF NEURONS GO FROM ONE STATE TO ANOTHER STATE TO ANOTHER STATE, HERE IS THE TRANSITION, YOU CAN SEE THAT ONE WENT FROM FIRING A LOT TO FIRING LITTLE TO FIRING NOTHING, ANOTHER WENT FROM FIRING NOTHING TO FIRING A LOT, ET CETERA, ET CETERA. YOU CAN SEE THE TRANSITION IN THE DATA. FURTHERMORE, YOU CAN SEE THAT MULTIPLE NEURONS, ABOUT 50% OF THE ENSEMBLE, CHANGE RATE SUDDENLY AND SIMULTANEOUSLY AT ANY STATE CHANGE. NOW, AGAIN, IF YOU ARE FORCED TO SIT THROUGH A LOT OF ENSEMBLE CODING TALKS, THIS IS SOMETHING THAT WE'RE VERY PROUD OF. FOR INSTANCE, WHEN YOU SEE A TALK ON, SAY, REPLAY IN THE HIPPOCAMPUS, WHAT'S OFTEN HIDDEN IN THOSE THINGS IS THE FACT THAT MAYBE 10% OF THE NEURONS THAT WERE RECORDED WERE SOMEHOW INVOLVED IN THE POPULATION PROCESS. THIS IS NOT SPARSE. MOST OF THE NEURONS WE'RE REPORTING FROM ARE INVOLVED IN EACH STATE CHANGE, WHICH MEANS THAT ALMOST EVERY NEURON THAT WE RECORD FROM IS INVOLVED IN THIS PROCESS TO SOME DEGREE, AND FURTHERMORE, WE CAN RECORD A BUNCH OF TRIALS AND SEE THE SAME THING OVER AND OWE AGAIN. ONE OF OVER AGAIN. ONE OF THE DOWN SIDES IS YOU CAN ONLY DELIVER A STIMULUS EVERY FINK FEN TO 30 SECONDS, THEN YOU HAVE AN ANIMAL THAT'S GOING TO GET FULL, BORED AND TIRED WITHIN A HALF AN HOUR. SO WHAT YOU CAN SEE IS FOR THE SUCROSE TRIALS, THEY ALL WENT THROUGH ESSENTIALLY THE SAME STATES. YOU ALSO GOT NEWS STATE STRUCTURES IN RESPONSE TO THE OTHER STIMULI, AND FURTHERMORE, AS EXPECTED, YOU GOT SITUATIONS WHERE IN ONE TRIAL OF SODIUM CHLORIDE, THIS STATE 2, STATE 3 TRANSITION HAPPENED AT THIS TIME POINT. AT THE VERY NEXT TRIAL, IT HAPPENED MUCH LATER. SO THAT DIVIDING POINT BETWEEN WHEN THIS TRANSITION OCCURRED CHANGED DRASTICALLY FROM TRIAL TO TRIAL. WHY IS THAT IMPORTANT? IT'S IMPORTANT BECAUSE IF YOU AVERAGE ACROSS THESE TRIALS, YOU ARE AVERAGING ACROSS SYSTEMS THAT ARE IN DIFFERENT STATES ON DIFFERENT TRIALS. AND MORE SPECIFICALLY, IF YOU GO BACK TO THIS PICTURE AND THIS RAMP, AND NOW YOU SAY WHAT -- IF WE LOOK AT EACH OF THESE TRIALS INDIVIDUALLY, YOU MIGHT SEE -- AND YOU LOOK FOR WHEN THE STATE THAT IS ACTIVE HERE COMES ON, HERE IS AN EXAMPLE WHERE WE DID A SET OF 10 TRIALS THIS, IS THE HIDDEN MARK ON MODEL SOLUTION SHOWING TRANSITION INTO THIS LATE STATE, AND YOU CAN SEE ON EACH, THIS TRANSITION HAPPENED VERY SUDDENLY PU IT BUT IT HAPPENED ON WIDELY DURCH TIMES FROM TRIAL TO TRIAL AND IF YOU AVERAGE THESE TOGETHER, YOU GET WHAT LOOKS LIKE A RAMP OF PROBABILITY. SO THE PROBLEM HERE IS, IF THIS IS THE WAY THINGS ACTUALLY WORK. IF YOU HAVE SUDDEN TRANSITIONS THAT HAPPEN AT SLIGHTLY DIFFERENT TIMES IN DIFFERENT TRIALS AND YOU AVERAGE THEM TOGETHER, YOU GET WHAT LOOKS LIKE A RAMP, BUT ISN'T. AND SO IN FACT, WE THINK THAT THIS WHOLE RAMPING IDEA WAS JUST A MISTAKE, AN ARTIFACT OF OLD OLD-FASHIONED ANALYSIS. MORE IMPORTANTLY, IF THIS IS WHAT'S ACTUALLY OCCURRING, THAT GIVES US A GREAT TOOL, BECAUSE IF, IN FACT, WE HAVE A SUDDENLY APPEARING PALATABILITY STATE, TEN WE CAN ACTUALLY START STUDYING IN SINGLE TRIALS HOW THAT APPEARANCE RELATES TO BEHAVIOR. SO FIRST WE WANT TO DO FURTHER TESTING TO MAKE SURE THAT WHAT'S APPEARING SUDDENLY IS, IN FACT, THE PALATABILITY STATE. AND SO HERE IS ANOTHER DATASET, THIS IS COLLECTED BY MY EX-GRADUATE STEUBT BRIAN SED A/K/A SOMEWHERE HERE ON CAMPUS, AND BRIAN COLLECTED TASTE RESPONSES AND SHOWED AS WE'VE SEEN BEFORE THAT WHEN YOU LOOK AT THESE THE NORMAL WAY, THE CORRELATION WITH PALATABILITY RISES BETWEEN .5 SECONDS AND ABOUT ONE SECOND. AND THEN HE WENT AND HE TOOK THESE EXACT DATA, AND HE DID HMM ON THEM AND SO THIS IS A SCHEMATIC OF THE HMM SOLUTIONS SHOWING THE STATES AND THE PROBABILITY OF THE STATES. HE BASICALLY MADE AN ASSUMPTION, WHICH IS THE STATE THAT IS MOST RELIABLY OUT -- AT THIS TIME POINT IS THE PUTATIVE PALATABILITY STATE. IN THIS KAI IT IS THE STATE -- ALL HE DID WAS SOMETHING VERY SIMPLE. HE IDENTIFIED IN EACH TRIAL WHEN THAT STATE CAME ON. AND SO THIS WAS -- WE DID THIS, BY THE WAY, WHEN IT GOT TO BE P EQUALS 1, P EQUALS .5, WE DID THIS A NUMBER OF WAYS. EVERYTHING I TELL YOU IS ROBUST TO ANY OF THOSE DIFFERENT MANIPULATIONS. THEN BRIAN DID A VERY, VERY SIMPLE MANIPULATION OF THE DATA. HE NUDGED THE DATA AROUND SO THAT INSTEAD OF BEING LINKED TO THE TIME OF TASTE DELIVERY, NOW ALL OF THE TRIALS WERE ORIENTED TO THE ONSET OF THAT STATE. THIS IS A REALLY SMALL PUSH. THE AVERAGE MOVEMENT OF A TRIAL WAS ABOUT 200, 250 MILLISECONDS, BUT SOME TRIALS HAD TO GET MOVED MUCH MORE. ONCE HE HAD THE DATA REARRANGED LIKE THIS, THIS VERY SMALL CHANGE, HE THEN WENT BACK AND REDID THE ANALYSIS OF HOW FAST PALATABILITY COMES ON, AND WHAT HE FOUND IS THAT BY DOING THIS, HE MASSIVELY INCREASED THE SPEED WITH WHICH PALATABILITY APPEARS. THE SPEED OF THAT TRANSITION. SO WHEREAS BEFOREHAND, IT WAS -- IT TOOK, SAY, THIS LONG TO GO FROM LOW TO HIGH PALATABILITY, THIS TIME NOW IT TAKES LESS THAN A THIRD OF THE TIME. IT'S A VERY SUDDEN TRANSITION. SO WE THEN WENT ON AND DID A WHOLE BUNCH OF TESTING, THE QUESTION IS HOW SUDDEN. WE ARE NOT FOOLS AND WE KNOW THAT THERE ARE ACTUALLY A LOT OF COMPLEXITY TO THIS ANALYSIS AND A LOT OF DANGER IN USING ANALYSIS LIKE THIS. ONE DANGER, AND BY THE WAY, THERE IS THE FACT THAT THIS IS THE RISE TIME OF THE CURVE UNDER NORMAL CONDITIONS AND THIS IS THE RISE TIME WHEN YOU'VE MANIPULATED -- WHEN YOU'VE MOVED THE DATASET SO YOU'RE LOOKING AT THE TRANSITION ITSELF. BUT THE PROBLEM; ONE OF THE PROBLEMS, IS THAT HMM WILL SHARPEN CRAP DATA. THAT'S WHAT IT'S THERE FOR. IT'S THERE TO TRY TO FIND MOMENTS IN WHICH THINGS CHANGE AND KEY ON TO THEM. EVEN IF YOUR DATA DOESN'T TRULY HAVE ANY SUDDEN TRANSITIONS, IT WILL FIND WHAT IT CAN AND IT WILL INEV BLI SHARPEN THINGS TO SOME DEGREE. SO IT'S IMPORTANT THAT WE SHOW THAT THIS WAS GENUINE, THAT THIS ISN'T JUST OUR FANCY ANALYSIS MAKING SOMETHING HAPPEN THAT OUR FANCY ANALYSIS DOES. THE LAST TIME I GAVE THIS TALK, BY THE TIME I WAS DONE TALKING ABOUT THIS, PEOPLE HAD FALLEN ASLEEP. THE REAL TRANSITIONS ARE SIGNIFICANTLY FASTER THAN TRIAL SHUFFLED DATA, WHERE YOU TAKE THE DATA AND YOU MOVE SPIKE TRAWNS TRAINS AROUND SO THAT YOU KEEP THE GENERAL DYNAMICS OF THE THREE PHASES BUT YOU RUIN THE WITHIN-TRIAL COHERENCE, AND BASICALLY IF YOU DO THAT, YOU RUIN THE SHARPENING. FURTHERMORE, WHEN WE SIMULATE DATABASED ON THE PSDHs, SO WE SIMULATE DATA THAT HAS THE THREE PHASES BUT NO CORRELATION BETWEEN NEURONS AND NO SUDDEN TRANSITIONS, WE DO NOT GET THIS INCREASE, WHICH MEANS THAT THE HMM IS SHARPENING OUR DATA BECAUSE THOSE TRANSITIONS ARE ACTUALLY THERE IN OUR DATA. THE BUT THE OTHER PROBLEM IS THAT THE WHOLE ANALYSIS ALSO SMOOTHS, SO THIS ANALYSIS WILL SHOW YOU TRANSITIONS BUT IT WILL AUTOMATICALLY INTRODUCE A LITTLE BIT OF A SMOOTHING ANY TIME YOU DO AN ANALYSIS THAT MOVES THROUGH A DATASET, IT SMOOTHS IT, SO WE DID ONE MORE TEST AND SHOWED THAT THE REAL TRANSITIONS IN OUR REAL DATA HAPPEN EVERY BIT AS FAST AS HMM-BASED ANALYSES OF STEP FUNCTION SIMULATIONS, WHICH MEANS THAT WHEN WE CREATED DATA THAT WERE PERFECT, THAT WENT FROM ONE STATE TO ANOTHER, INSTANTANEOUSLY AND FULLY COHERENTLY THAT LOOKED EXACTLY LIKE OUR REAL DATA. SO FOR ALL INTENTS AND PURPOSES, AS FAR AS WE CAN TELL, THIS TRANSITION IS INSTANTANEOUS. BASICALLY THE SET OF NEURONS GO FROM BEING -- HAVING NO PALATABILITY IN THEM TO SUDDENLY WI IS WHICH IS GREAT BECAUSE NOW IT GIVES US SOMETHING TO LOOK AT SINGLE TRIAL RELATIONSHIP TOO BEHAVIOR, SO I WANT TO BRIEFLY RETURN TO THE BEHAVIOR ITSELF. HERE IS A RAT IN A CAGE. THIS RAT HAS BEEN FIT BY MY EX-POSTDOC JEN LEE WITH ELECTROMYOGRAPHY ELECTRODES IN ITS JAW SO YOU CAN ACTUALLY SEE THE JAW MOVEMENTS, WHICH IS IMPORTANT BECAUSE RATS TEND TO REAR AND MOVE AND IT'S HARD TO SEE WHAT'S GOING ON, BUT THE COOL THING IS THAT WHEN YOU'RE TALKING ABOUT THESE MOUTH BEHAVIORS AND YOU GET THE EMG, YOU CAN SEE THEM VERY CLEARLY IN THE EMG SIGNAL, AND IN PARTICULAR, YOU CAN SEE THE SIGNAL THAT IS THE RAT REJECTING THE TASTE. WHEN THE RAT DECIDES THAT WHAT'S IN ITS MOUTH IS DISGUSTING, IT WILL DO WHAT'S CALLED A GAPE. ACTUALLY IT WILL DO A STRING OF GAPES. A BIG YAWNING FACE INSIDE THE MOUTH, THE TONGUE IS ROLLING FORWARD TO GET THE TASTE OUT THIS HAPPENS AT N. A SLOW, RHYTHMIC PATTERN. YOU CAN SEIZE EE SEE EASILY SEE THAT IN TH E EMG. FIRST YOU GET NON-DISTINCT LICKS OF ITS CHOPS, SOMETHING IS IN THE MOUTH, IT'S ROLLING IT AROUND, THEN, BAM, THERE'S A GAPE, THERE'S A GAPE, THERE'S ANOTHER GAPE, THAT IS THE RAT SAYING I HATE IT, I WANT IT OUT. YOU'LL NOTICE, BY THE WAY, IN THIS TRIAL, IT HAPPENED ONLY ABOUT 1,800 MILLISECONDS AFTER THE TASTE HIT THE TONGUE. ONE OF THE THINGS ABOUT THIS BEHAVIOR IS UNDER NORMAL CIRCUMSTANCES, IT'S INCREDIBLE, THE VARIABLE IN LATENCY. ON SOME TRIAL, IT HAPPENS AS EARLY AS 500 MILLISECONDS, ON SOME TRIALS, IT TAKES 2,000 MILLISECONDS. THIS IS A CHALLENGE UNDER MOST CIRCUMSTANCES BUT WE THINK -- WELL, OUR THOUGHT WAS, THIS WAS GOING TO MATCH UP WITH THE VARIABILITY IN THE NEURAL ACTIVITY. AND SO THAT'S WHAT I'M GOING TO SHOW YOU NEXT. I SHOULD POINT OUT THAT THIS IS LIKE OUR EVERYDAY LIFE. WE LIKE TO THINK WHEN WE'RE STUDYING OUR ANIMALS IN THE LAB, THEY'RE LIECT LITTLE MACHINE, YOU PUT THE STIMULUS ON, YOU GET THE RESPONSE, IT SHOULD HAPPEN AT THE SAME TIME EVERY TIME, BUT OF COURSE IN YOUR OWN INTRO SPECS, THAT'S NOT WHAT HAPPENS. WHEN YOU'RE WATCHING TV AND AN ACTOR COMES ON THE SCREEN AND YOU SAY I KNOW WHO THAT ACTOR IS, IT'S -- AND IT COMES TO YOU SUDDENLY, IT'S UMA THURMAN. THE NEXT ONE COMES ON THE SCREEN, ANOTHER BLOND ACTOR AND YOU'RE LIKE, THAT'S, THAT'S, THAT'S SOMEBODY ELSE. IT'S GOING TO HAPPEN SUDDENLY, IT'S NOT GOING TO TAKE THE SAME AMOUNT OF TIME. THIS IS THE WAY WE ACTUALLY WORK. IN REAL LIFE, ANIMALS LIKE OURSELVES AND OUR RATS, THINGS DON'T HAPPEN ACCORDING TO A NICE RELIABLE INTERNAL CLOCK. SO WHAT WE WANTED TO DO NOW WAS TUS WHETHER THIS VARIABILITY AND THE NEURAL VARIABILITY WERE LINKED, BECAUSE AGAIN, IF YOUR DYNAMICS MEAN ANYTHING, YOU HAVE TO SHOW THAT THEY'RE RELATED TO BEHAVIOR, SO THAT'S WHAT WE DID. WE TOOK YET ANOTHER DATASET, AND WE DID HMM ON IT. SO THIS IS ONCE AGAIN A PICTURE OF AN HMM ANALYSIS OF A SINGLE TRIAL. I HAVE IN THIS CASE MADE A NICE GREEN DASH, THE ONSET OF THE PALATABILITY RELATED STATE THAT WE'VE ALREADY BEEN STUDYING, IT OCCURRED HERE, THEN I WENT AND LOOKED AT BEHAVIOR, BRIAN SED A/K/A DID IT ALL. YOU CAN SAY THAT THAT STATE APPEARED AT THIS TIME POINT AND THOSE ARE THE GAPES PRODUCED BY THE ANIMAL. ALL THE STUFF I'M SHOWING YOU NOW IS ABOUT GAIPS. I GAPES. IT LOOKS LIKE THE SAME THING IS TRUE FOR THE TASTE THE ANIMAL REALLY LOVES BUT IT'S HARDER TO RECORD THOSE IN EMG. BUT YOU CAN SEE THAT GAPES STARTED RIGHT AFTER THAT STATE CAME ON. HERE ARE THE VERY NEXT -- SO WE CALL THAT THE GAPE PERIOD. THEER ARE THE VERY NEXT THREE TRIALS OF QUININE. YOU CAN SEE WHEN THAT TRANSITION CAME ON EARLIER, THE GAPES CAME ON EARLIER. WHEN THAT TRANSITION CAME ON LATER, THE GAPES CAME ON LATER. HERE IS THE ENTIRE SESSION OF ABOUT 25 QUININE TRIALS. WHAT YOU CAN SEE IS THAT WHEN YOU MAP TIME OF NEURAL TRANSMISSION AGAINST TIME IT STARTED GAPING ARE OUR BUT FOUR LONELY NOISY TRIALS, IT'S ALWAYS JUST AFT NEURAL TRANSITION THE ANIMAL BEHAVE. THE LATENCY IS ABOUT 300 MILLISECONDS, SO BASICALLY THAT TRON SITION OCCURS AND ABOUT 300 MILLISECONDS LATER, THE ANIMAL RESPONDS. SO USING THESE DYNAMICS IN SINGLE TRIALS, WE CANNOT ONLY TELL YOU WHAT BEHAVIOR THE ANIMAL IS GOING TO DO, WE CAN TELL YOU WHEN, DESPITE THE FACT THAT THE BEHAVIORAL LATENCY, AS I'VE SAID, VARIES FROM 500 MILLISECONDS TO WELL OVER A THOUSAND. YOU WANT TO TALK ABOUT GOING FROM CORRELATION TO CAUSATION, THE FIRST ONE WE DO AND BECAUSE WE'RE PSYCHOLOGISTS, WE LIKE WORKING THIS THIS SORT OF THING, WE WORK WITH THE BEHAVIOR. WE MANIPULATED IT BY CUING. WORK OF JEN LEE AGAIN, SHE BASICALLY SIMPLIFIED THINGS, DELIVERED STRONG OR DILUTE CONCENTRATIONS BUT SHE ALSO DID SOMETHING ELSE. EVERY TIME SHE WAS ABOUT TO DELIVER THE REALLY NOXIOUS QUININE SOLUTION, SHE'D PLAY A TONE. SO JUST BEFORE THE HARSH QUININE CAME ON, THE ANIMAL WOULD HEAR A TONE. WHAT HAPPENS ACROSS THAT TIME IS THE RAT LEARNS, AND WHAT IT LEARNS IS SOMETHING NASTY IS COMING, AND WHAT THAT MEANS IS THAT ACROSS A SINGLE SESSION, THE LATENCY TO THOSE GAPES DROPS BY ABOUT 150 MILLISECONDS. 150 MILLISECONDS. SO THAT MEANS A THA ACROSS THE SESSION THE AN MAN AS THE ANIMAL LEARNS, I T GAIPS EARLIER. IF YOU LOOK AT THIZATION SESSIONS WITHOUT QUEUES, YOU CAN SEE THERE'S VIRTUALLY NO CHANGE. THE CUING CHANGES THE BEHAVIORAL LATENCY. JEN THEN WENT BACK AND LOOKED AT THE ORIGINAL DATA AND SAID WHAT HAPPENS TO THE TIME OF THAT TRANSITION AND IT TURNS OUT THE TIME OF TRANSITION CHANGES AT THE ANIMAL LEARNS. SO AS THE ANIMAL'S GAPING GOES EARLIER, THE NEURAL AK TUFF GOES EARLIER. SO THAT MATCHES UP. THEN I WANT TO TALK TO YOU ABOUT GOING FROM CORRELATION TO CAUSATION DOING WHAT PEOPLE ARE MORE PRIME TO BE INTERESTED IN, WHICH IS MANIPULATING BEHAVIOR THROUGH GC PERTURBATION USING OPT TIGENETICS. WE'VE BEEN LOOKING AT WHAT HAPPENS WHEN YOU KNOCK OUT GC NEUROACTIVITY. IN JEN'S PAPER, SHE SHOWED THAT WHEN YOU KNOCK OUT DP. C, YOU, IN FACT, CHANGE WHETHER OR NOT THE ANIMAL GAPES, BUT I'M NOT GOING TO SHOW YOU THOSE DATA BECAUSE WE'RE GOING BEYOND, AND ONE OF THE THINGS THAT BUGGED ME ABOUT WHERE MY LAB IS AT THIS PARTICULAR MOMENT IS THAT WE'RE JUST GETTING READY TO PUT TOGETHER THE NEXT SET OF PAPERS. I USUALLY LIKE GIVING A LOT OF PRELIMINARY DATA IN MY TALKS AND WE'RE NOT QUITE THERE YET, BUT I WANT YOU TO KNOW ABOUT WHAT'S GOING ON, AND SO WHAT ONE OF MY NEW GRADUATE STUDENTS IS DOING IS HE IS ACTUALLY NOT JUST KNOCKING OUT TASTE CORTEX, HE'S DOING IT FOR VERY SMALL INTERVALS. HE'S PROVIDING 500 MILLISECONDS OF ARCH T INHIBITION OF GUSTATORY CORTEX, AND WHAT HE FINDS IS THAT WHEN THAT INHIBITION COMES BEFORE AND DURING THAT SUPPOSED TRANSITION IS LATE STATE, HE BLOCKS THE CHANGE INTO GAPING. IF HE DOES IT TOO EARLY, EARLIER, IT DOESN'T HAVE ANY IMPACT, IF BUT IF HE NAILS THAT TRANSITION TIME, WITH HALF A SECOND OF NEURAL INHIBITION, BASICALLY HE REDUCES THE LAKELY HOOD OF AND PUSHES BACK IN TIME THE GAPING. SO IT'S NOT JUST THAT CHANGE IN THE BEHAVIOR CHANGES THE NEURAL ACTIVITY. MESSING WITH THE NEURAL ACTIVITY MESSES WITH THE BEHAVIOR. FURTHERMORE, PERTURBATION, I HAVE NO SUCH IMPACT, AND I JUST WANT TO POINT OUT THAT ONE OF MY POSTDOCS IS ALSO LOOKING AT WHERE THIS TRANSITION MIGHT BE COMING FROM, AND IT TURNS OUT IT'S COMING FROM INPUT FROM THE BASAL LATERAL AMYGDALA. WE'RE VERY EARLY IN THIS PROJECT, BUT IF YOU LOOK AT THE CORRELATION WITH PALATABILITY, THIS BLACK -- I JUST GOT THESE DATA TODAY. THE BLACK IS NORMAL TRIALS, YOU CAN SEE THE APPARENT RAMP, AGAIN, THIS IS LOOKING ACROSS TRIALS, AND THE RED IS WHAT HAPPENS WHEN YOU INACTIVATE JUST THE IP PUTS THE INPUTS TO CORTEX FROM AMYGDALA. SO IT TURNS OUT THAT PART OF THIS PROCESS IS BEING RUN BY THE AMYGDALA SO I'VE TO THE TO GIVE YOU AN OBLIGATORY SLIDE, THEY DON'T JUST CODE THE TASTE. RATHER, THEY REFLECT IDENTITY AND PALATABILITY IN SUCK SE FIF EPICS OF THE DYNAMIC. THE ONSET OF PALATABILITY CODING IS A SUDDEN SEMI BE TRANSITION THAT AS FAR AS WE CAN TELL HAPPENS INSTANTANEOUSLY. BY GETTING AHOLD OF THIS, WE CAN SHOW THAT THIS IN TURN DRIVES BEHAVIOR, PERHAPS BY MODULATING A BRAINSTEM CPG AND, IN FACT, I WANT TO HUT PUTT THIS IN CONTEXT, IF I CAN DO NOTHING ELSE WITH MY CAREER, I'D LIKE TO RESCUE THE WORD MODULATION FROM THE NEUROSIGH INS SCRAP HEAP. IN SITU, MANY CPGs STUDIED IN MANY DIFFERENT SYSTEMS CHOOSE AMONG MULTIPLE RHYTHMS, HERE IS A SCHEMATIC OF A CPG, AND CAN YOU SEE THAT IT HAS AN IMPACT ON MOTOR NEURONS BUT IT ALSO RECEIVES EXTRINSIC INPUT AND THAT IS THE TOP-DOWN MODULATION. HERE'S A MORE SPECIFIC EXAMPLE, WORK FROM EVE MARTYR, THE SOMATOGASTRIC BEGAN GLEAN FROM LOBSTERS AND CRABS, A GROUP BETWEEN 20 AND 30 NEURONS THAT IS THE CENTRAL GENERATOR FOR THE RHYTHMS THE ANIMAL'S STOMACH GOES THROUGH WHEN GRINDING UP FOOD. WHAT MOST OF HER CAREER HAS BEEN BASED ON IS HOW THAT STUFF TAKES SENSORY INPUT, OUTPUT INTO THE MUST ELSE, BUT ALL OF THE DIFFERENT SORTS OF MODULATION THAT ARE TOP-DOWN THAT HELP CHOOSE THE RHYTHM THAT THE CENTRAL PATTERN GENERATOR PRODUCES. WHICH IS TO SAY, THE CENTRAL PATTERN GENERATOR IS VERY SIMPLE AND ILTS RIGHT THERE, BUT THE CHOICE OF WHAT IT DOES COMES A GREAT DEAL FROM TOP DOWN INPUT. OUR ARGUMENT IS THAT TASTE CORTEX AND PROBABLY AMYGDALA AND HYPOTHALAMUS AND BST ARE FOUR -- STRUCTURES THAT FEEDBACK DOWN TO THE CENTRAL PATTERN GENERATOR FOR MOUTH MOVEMENTS IN THE RODENT AND AFFECT WHICH ONE IS PRODUCED. SO THAT'S THE END OF PART 1 OF MY TALK. NOW I'D LIKE TO CHANGE GEARS SLIGHTLY AND TELL YOU THAT THAT'S NOT ALL THAT GC MOD LATES. IF THE LAST PART OF THE TALK WAS SURPRISING TO YOU, THIS ONE IS GOING TO BE KIND OF CRAZY BECAUSE WHAT WE'RE GOING TO SHOW YOU IS THAT GC IS A PART OF OLFACTION. SO IF THE SCHEMATIC SEEMED RIDICULOUSLY SIMPLISTIC, HERE'S ONE THAT'S EVEN MORE SIMPLISTIC. FROM THE MOUTH, THINGS GO TO THE TASTE SYSTEM, FROM THE NOSE, THEY GO TO THE OLFACTORY SYSTEM. WE'VE ALL LONG KNOWN THAT THE OLFACTORY SYSTEM INFLUECES THE TASTE SYSTEM. WHEN YOU HAVE A COLD AND YOU CAN'T SMELL FOR A WEEK, THINGS DON'T TASTE RIGHT. AND IN FACT, THIS HAS BEEN SHOWN IN THE BRAIN, LOTS OF STU CAN STUDIES, FROM DEEP DOWN IN THE BRAINSTEM, THESE ARE JUST -- THIS IS JUST AN EXAMPLE. SHOWED THAT IN THE MEDULLARY FIRST TASTE LEVEL INPUT, YOU SEE OLFACTORY RESPONSES. UP IN THE CORTEX, ANOTHER OF MY EX-POSTDOCS WITH HIS POSTDOC CHAD SAUMELSON INSTEAD SHOW TSH THIS IS WHAT YOU WOULD EXPECT BECAUSE OLFACTION INFLUENCES TASTE VIA THAT VERY SPECIFIC ARROW. WHAT I'M GOING TO TELL YOU NOW IS THAT THE OPPOSITE OCCURS. THAT IN FACT, IN ADDITION, THE TASTE SYSTEM INFLUENCES THE OLFACTORY SYSTEM. I'M GOING TO MORE SPECIFICALLY TALK ABOUT G.C. AND OLFACTORY CORTEX. AND THIS IS LARGELY THE WORK OF MY EX-POSTDOC YOST MEIER. FIRST OF ALL OLFACTORY NEURON DOES -- THIS IS JUST ONE EXAMPLE FROM YOST'S WORK, BASICALLY THIS IS AN OLFACTORY CORTEX NEURON THAT HAS A VERY STRONG RESPONSE TO A SOUR STIMULUS, STRONGER THAN THE OTHER. HE SAW A RANGE OF DIFFERENT TYPES OF RESPONSES, BUT IN FACT HE SAW A LOT OF TASTE RESPONSES IN OLFACTORY CORTEX. NOW THE FIRST THING THAT YOU -- IF YOU ARE AN OLFACTORY RESEARCHER WILL SAY, YOU KNOW, YOU PUT SOMETHING ON THE TONGUE AND YOU'RE GOING TO GET UP INTO THE NOSE VIA RETRO NASAL PASSAGES, SO HOW DO YOU KNOW THAT YOU DON'T ACTUALLY HAVE AN OLFACTORY RESPONSE? AND SO WHAT WE DID WAS WE WENT AND WE TESTED WHETHER THIS WAS GENERAL WITHINLY TASTE AND WE TESTED IT BY KNOCKING OUT THE TONGUE. THIS IS JUST AN EXAMPLE OF ACROSS HIS WHOLE SET ARE RECORDED OLFACTORY NEURONS WHEN THE ANIMAL WAS INTACT, YOU CAN SEE THE RESPONSES ARE ABOVE ZERO. THIS IS JUST SHOWING THERE WERE TASTE RESPONSES. WHAT HE DID THEN WAS -- YOST HAD PREENTLY HAD A CHILD WHO WAS HAVING TEETHING PROBLEMS. HE STOLE THAT CHILD'S AMBESOL, TOPICAL SODIUM CHANNEL BLOCKER, SPREAD IT ON THE TONGUES OF HIS RATS SO THAT THEY COULD NO LONGER TASTE ANYTHING, AND ESSENTIALLY THE RESPONSES DISAPPEARED. SO WITHOUT THE TONGUE BEING ACTIVE, WE DID NOT GET THESE RESPONSES IN OLFACTORY CORTEX. THEN UNTIL YOU COMPLETE, HE ALSO WENT AND TOOK THE GROUP OF ANIMALS AND DECILIATED THEM. THE CILIA ARE THE PARTS OF THE NEURON THAT ARE PRIMARILY RESPONSIBLE FOR TRANSDUCING OLFACTORY STIMULI. YOU CAN BASICALLY PUT A DETERGENT UP THE NOSE, WASH AWAY THOSE CILIA AND TEMPORARILY RENDER THE ANIMAL -- WHEN YOU DO THAT, IT HAS NO INFLUENCE ON THE TASTE RESPONSES. NEITHER THOSE LOOKED AT HOLISTICALLY OR IN TERMS OF TEMPORAL CODING. SO THESE ARE TRUE TASTE RESPONSES IN OLFACTORY CORTEX. SO HE THEN ASKED WHERE ARE THEY COMING FROM, HERE'S THAT SILLY DIAGRAM AGAIN SUGGESTING THEY MAY BE COMING FROM GUSTATORY CORTEX TO IN THIS CASE THEY CALLED IT -- THE FIRST THING HE DID WAS HE PUT GROUPS OF ELECTRODES IN BOTH STRUCTURES, RECORDED SIMULTANEOUSLY, AND WHEN HE FOUND PAIRS OF NEURONS, ONE IN GC AND ONE IN PC, THAT BOTH HAD TASTE RESPONSES, HE ASKED WHAT'S THE LEAD LAG STRUCTURE? COMES ON AT THE SAME TIME OR NOT? AND WHAT HE FOUND WAS IN ALL BUT ONE CASE, GC LED PC, WHICH IS TO SAY THAT WHEN YOU HAD A PAIR OF NEURONS, ONE IN TASTE CORTEX, ONE IN OLFACTORY CORTEX, BOTH OF WHICH SHOW TIS RESPONSES, IT'S ALMOST ALWAYS IN TASTE CORTEX FIRST. WHAT YOU REALLY WANT TO DO THEN IS GO BACK AND KNOCK OUT TASTE CORTEX, MAYBE THE GREEN IS FOR THE GREEN LASER THAT IS USED WHEN YOU IN FACT THAT NUCLEUS WITH ARCH T, SO HE RECORDED FROM PC WHILE KNOCKING OUT GC, AND WHAT YOU SEE HERE IS IN THE INTACT ANIMAL, A RESPONSE THAT IS STRONG TO BITTER AND WEAK TO SALTY, SO THIS IS A TASTE RESPONSE IN PURE FORM CORTEX. WHEN HE KNOCKS OUT TASTE CORTEX, THAT RESPONSE IS GONE. IN OUR HANDS, ABOUT TWO-THIRDS OF THE TASTE RESPONSES ARE UTTERLY LOST, WHEN YOU KNOCK OUT TASTE CORTEX. SO MOST OF THE OLFACTORY CORTEX TASTE RESPONSES DISAPPEAR WITHOUT TASTE CORE SEX THERE, WHICH IS STRONG EVIDENCE THAT, IN FACT, THEY'RE COMING FROM THERE. MIND YOU, WE ARE NOT SAYING THEY'RE COMING FROM THEIR MONO SYNAPTICALLY. WE HAVE NO SUCH EVIDENCE ON THAT END AND FURTHERMORE, I DOUBT IT. BUT THESE RESPONSES DON'T GET TO OLFACTORY CORTEX WITHOUT FIRST GOING THROUGH TASTE CORTEX. BUT THEN THINGS GET KINKY. YOST HAS THE SETUP, HE HAS THE APPARATUS. WHY JUST LOOK AT TASTE RESPONSES? WHAT HAPPENS TO OLFACTORY RESPONSES IN OLFACTORY CORTEX WHEN YOU KNOCK OUT TASTE CORTEX? WELL, HERE IS ONE EXAMPLE OF A NEURON THAT HAD A NICE BIG JUICY RESPONSE TO AN OLFACTORY STIMULUS. I'LL BE HONEST AND SAY I DON'T REMEMBER WHAT THE OLFACTORY STIMULUS YOST HERE USE WAS, AND YOU CAN SEE WHEN HE KNOCKED OUT BY ELIMINATING IT, YOU SIMPLY LOST A GREAT DEAL OF THAT RESPONSE. SO FOR SOME REASON, HERE WE HAVE GC INKNOCKING OUT -- BUT DON'T WORRY, HE ALSO SAW THE OPPOSITE. HE SAW NEURONS WHERE THERE WAS NO RESPONSE TO THE OLFACTORY STIMULUS HE KNOCKED OUT GC. IN FACT, WHEN YOU KNOCK OUT GC, YOU GAIN AND LOSE AN EQUAL NUMBER OF OWE FACTORY RESPONSES WHICH DISTINGUISHES IT FROM WHAT HAPPENS TO TASTE RESPONSES. WHEN YOU KNOCK OUT GC, YOU CHANGE THE WAY THE NETWORK RESPONDS. SOME RESPONSES GET BIGGER, SOME GET SMALLER. I'D BE HAPPY TO TALK WITH YOU AT GREAT LENGTH ABOUT HOW SIMPLE THIS IS TO EXPLAIN AT THE NETWORK LEVEL, IF -- WHEN IT'S A ROOM FULL OF THEORISTS, THEY KNOW EXACTLY WHY THIS HAPPENED OR AT LEAST ONE SIMPLE HYPOTHESIS. THE POINT HERE IS, THOUGH, THAT SOMEHOW GC IS MODULATING OLFACTORY PROCESSING IN PC. BUT AGAIN, OKAY, THAT'S REALLY CUTE BUT IT DOESN'T MEAN A THING IF IT CAN'T BE ATTACHED TO BEHAVIOR. KEEPING IN MIND THE ROUTE FROM THE PC TO THE NOSE IS INTACT, THIS IS ACTUALLY A SURPRISING RESULT. SO HE WENT ON AND ACTUALLY TESTED OLFACTION. IN FACT, WE'VE DONE THIS IN A COUPLE DIFFERENT PARADIGMS. WE DECIDED TO CHECK WHETHER WE COULD ACTUALLY SEE BEHAVIORALLY THE IMPACT OF KNOCKING OUT GC ON OLFACTION, LOOKING AT A GREAT TASK CALLED SOCIALLY TRANSMITTED FOOD PREFERENCE. LET'S SAY YOU TAKE AR -- THIS IS WHAT HAPPENS WHEN YOU LET AN ART PEOPLE AT YOUR JOURNAL DRAW YOUR PICTURES FOR YOU. THIS SUPPOSED RAT IS EATING A FOOD. YOU THEN SET UP A SITUATION WHERE THIS RAT HAS A LITTLE TETE-E-TETE WITH A SECOND RAT. I'M ASKING YOU TO TRUST ME, WHAT HAPPENS IS THE FIRST RAT BREATHS ON THE SECOND RAT. IT'S ALL OWE OLFACTION. THIS RAT SMELLS THE COMBINATION OF THE FOOD AND THIS OTHER RAT'S BREADTH AND BASICALLY SAYS IN HIS LITTLE RAT HEAD, WELL, RALPHIE HERE EIGHT THAT AND LIVED, AND IF YOU THEN GIVE THE SECOND RAT ACCESS TO THAT TASTE AND ANOTHER TASTE, HE WILL PREFER THE ONE THAT WAS DEN STRAIGHTED TO HIM. HE WILL LEARN A PREFERENCE. THIS HAPPENS IN A SINGLE TRIAL. FURTHERMORE, THIS HAPPENS EVEN IF WHAT RALPHIE HERE WAS EATING WAS BITTER. WHAT WE USED WAS RAW COCOA. IF ANY OF YOU HAVE EVER ACCIDENTALLY GRABBED BAKER'S CHOCOLATE INSTEAD OF HERSHEY'S, YOU KNOW RAW CHOCOLATE IS EXTREMELY BITTER. HE EATS IT BECAUSE HE DOESN'T HAVE A CHOICE, WE DON'T DO ANYTHING TO THIS RAT, WE DON'T BREAK ITS BRAIN, WE DON'T DO A THING TO IT. THE VERY FIRST TIME IT IS EXPOSED TO BITTER, IT DOES NOT REJECT IT, IT PREFERS IT. SO THERE IS THE TEST AND SO YOU CAN SEE THAT THERE IS THE ACTUAL DATA, THE TOTAL CONSUMPTION THAT IS THE DEMONSTRATED FOOD VERSUS THE UNDEMONSTRATED FOOD, THIS IS WORK OF MY EX-GRADUATE STUDENT SANTIAGO, YOU CAN SEE THERE IS A STRONG PREFERENCE THAT IS LEARNED, AGAIN, YOU CAN TAKE MY WORD FOR THE FACT THAT PRETRAINING, THERE WAS NO SUCH PREFERENCE. SO WHAT HAPPENS WHEN WE KNOCK OUT TASTE CORTEX? WELL, IT TURNS OUT THE ANIMAL DOESN'T -- THIS IS AN OLFACTORY TASK, BUT IF THE TASTE CORTEX OF GC IS KNOCKED OUT DURING TRAINING, DURING THE INTERVIEW BETWEEN ONE RAT AND THE OTHER RAT, NO PREFERENCE IS LEARNED. FURTHERMORE, IF YOU KNOCK OUT GC DURING TESTING, THE ANIMAL DOESN'T SHOW EVIDENCE OF ANY PREFERENCE. SO GC HAS TO BE THERE FOR THIS TASK TO WORK. NOW, AT THIS POINT, THIS IS ONE OF THE -- THIS IS THE MOMENT THAT YARA CROSSED INTO JEAN EXPWREEN JUST GENIUS. ONE IS THAT GC IS A PART OF THE OLFACTORY SYSTEM AND THE OLFACTORY INFORMATION IS LIVING THERE. ANOTHER IS THAT THE GC IS A NECESSARY PART OF THE LEARNING CIRCUIT. THAT WITHOUT THE GC THERE, THE ANIMAL DOESN'T LEARN A THING. IT COULD BE THE CASE THAT GC BEING CONNECTED UP TO A LOT OF OTHER SYSTEMS INVOLVED IN VALUE, GC IS IMPORTANT FOR CODING VALUE, THAT WITHOUT THE DP. C, THE ANIMAL JUST CAN'T TELL WHETHER SOMETHING IS YUMMY OR NOT. THE FOURTH HYPOTHESIS, THE ONE SUGGESTED BY YOST'S DATA, IS THAT GC MOD LATES OLFACTORY PROCESSING IN THE OLFACTORY SYSTEM. THAT ONE HYPOTHESIS PREDICTS SOMETHING SPECIAL. IF THAT HYPOTHESIS IS CORRECT, IF WE KNOCK OUT GC BOTH IN TRAINING AND IN TESTING, THE ANIMAL SHOULD DO FINE. WE SHOULD RESCUE LEARNING. BECAUSE THEN WHATEVER CHANGE YOU CAUSE IN OLFACTORY TRAINING PROCESSES HAPPENS AGAIN IN TESTING AND THE ANIMAL IS BASICALLY IN A STATE-DEPENDENT IF YOU STUDIED STONED YOU HAVE TO TAKE THE TEST STONED SORT OF SITUATION, AND THAT'S IN FACT WHAT HAPPENED. LET'S SAY THAT BANANA, YOU MADE IT TASTE LIKE CINNAMON BY KNOCKING OUT TASTE CORTEX, THEN WHEN YOU GET TO THE TEST, YOU KNOCK IT OUT AGAIN, HEY, IT SMELLS LIKE CINNAMON AGAIN, I HAVE LEARNED THAT I SHOULD PREFER CINNAMON -- SO THAT IS THAT WE ARE. THAT SHOWS THAT, IN FACT, TASTE CORTEX, GC, MOD LATES NOT JUST TASTE BEHAVIORS BUT OLFACTORY PERCEPTION AS WELL. WHAT'S IN PROGRESS, WORK BEING DONE BY MY GRADUATE STUDENT MEREDITH BLANKE NSHIP -- OLFACTORY STIMULI LET GET TO BE OLFACTORY EPITHELIUM IN TWO WAYS. THE OTHER IS RETRO NASAL, WHICH IS WHEN YOU HAVE SOMETHING IN YOUR MOUTH THAT IS VOLATILE AND YOU'RE CHEWING IT AND MOLECULES GO UP THE BACK OF YOUR THROAT TO THE OLFACTORY EPITHELIUM. WHAT MEREDITH IS CURRENTLY SHOWING IS THAT GC PERTURBATION HAS A MUCH LARGER IMPACT ON RETRO NASAL. IN FACT, HERE IS THE GRAPH. BASICALLY THE ANIMAL IS BEING GIVEN A FLUID IN ITS MOUTH THAT HAS NO TASTE. BUT HAS AN ODOR. THEN IS GETTING CALORIES FROM IT. AND IS LEARNING TO LIKE IT. WHAT YOU CAN SEE IS THAT THIS IS BEFORE -- THIS IS TRAINING AND THIS IS TESTING. AND THE GREEN LINE IS WHAT HAPPENS WHEN YOU'RE DOING IT ORTHONASALLY AND KNOCKING OUT GC. IN THIS TEST, THE ORTHONASAL PARADIGM, THE ANIMAL LEARNS IT JUST FINE, THE RETRO BASAL PARADIGM, THE ANIMAL DOESN'T LIVE. SO IT TURNS OUT THIS HAS VERY SPECIFICALLY TO DO WITH RETRO NASAL PERCEPTION, WHICH CAUSES SOME DIFFICULTIES THAT WE'RE STILL TRYING TO FIGURE OUT, BUT GC IS INVOLVED IN NOT SO MUCH TASTE AS FEEDING AND IT'S SOMETHING THAT COMES FROM SOMETHING THAT IS BEING CONSUMED CURRENTLY, SO WE THINK SOMETHING GOING ON, THAT THAT CHANGES THE NETWORKS INVOLVED SO GC BECOMES IMPORTANT. THIS IS REALLY EARLY STUFF. I JUST WANTED TO THROW IT OUT THERE. SO HERE'S MY SECOND OBLIGATORY SUMMARY SLIDE. GC MOD LATES NOT ONLY TASTE BEHAVIOR BUT ALSO OLFACTORY PROCESSING. TASTE INFORMATION REACHES OLFACTORY CORTEX FROM GUSTATORY CORTEX, REMOVAL OF SPONTANEOUS GC INPUTS, PROBABLY MODULATING OLFACTORY CORTEX NETWORK FUNCTION. THIS MODULATION CONSTITUTES A STATE-DEPENDENT -- WHEN YOU KNOCK OUT GC, YOU CHANGE THE WAY OLFACTORY SYSTEM PROCESSES AN ODOR. SO IF YOU KNOCK OUT GC AGAIN, YOU CHANGE IT AGAIN. SO THAT'S IT. THANK YOU FROM THE BEHAVIOR, LEARNING AND ELECTROPHYSIOLOGY OF CHEMO SENSATION LAB AT BRANDEIS UNIVERSITY. HERE IS THE LIST OF PEOPLE IN MY LAB. I'M EITHER GOING TO HAVE TO STOP TAKING PEOPLE OR REDUCE MY FONT SIZE. I'D LIKE TO SPECIFICALLY SHOUT OUT TO ALFREDO WHO DID ALL OF THE EARLY EMPIRICAL WORK, NOW A FACULTY MEMBER. LAUREN JONES, WHO IS THE PERSON WHO DID THE FIRST MODELING WORK, AND BRIAN SED A/K/A, CURRENTLY STILL A POSTDOC AT NATIONAL INSTITUTES -- AT NIDA WHO DID THE WORK ON HMM AND BEHAVIOR. HE WAS ASSISTED BY MY CURRENT GRADUATE STUDENT WHO DID THE MOST RECENT MODELING WORK, AND JENNIFER L.I. FINALLY, YARA SANTIAGO IS THE PERSON WHO DID THE SOCIAL TRANSMISSION WORK, YOST MEIER IS THE GUY WHO TOOK US INTO OLFACTION, AND THE NEWEST WORK, WHILE I DON'T HAVE ANY PLACE TO PUT THEIR PICTURES YET, MEREDITH BLANKENSHIP IS LOOKING AT ORTHOVERSUS RETRO, AND JOHN LIN IS LOOKING HOW DIFFERENT INPUTS TO GC MATTER. I'D LIKE TO SHOUT OUT -- BRANDEIS IS AN EXTREMELY COLLABORATIVE JOINT. I'D LIKE TO SPECIFICALLY NOTE PAUL MILLER. PAUL IS IN THE BIOLOGY DEPARTMENT, HE'S REALLY JUST A RECOVERING PHYSICIST, AND HE IS THE PERSON WHO IS RESPONSIBLE FOR MAKING SURE THAT ALL OUR COMPLEX ANALYSES ACTUALLY WORK. I CAN BARELY ADD. I'D ALSO LIKE TO ACKNOWLEDGE FUNDING FROM THE NIH AND IN PARTICULAR FOR THE NIDCD, THE NSF, AND THE SCHWARTZ FOUNDATION FOR COMPUTATIONAL LEARNING SCIENCE. THAT'S THE WHOLE TALK. I THANK YOU FOR LISTENING AND I'D BE HAPPY TO TAKE ANY QUESTIONS. [APPLAUSE] OR NOT. >> HOW MUCH TIME DOES THE ANIMAL HAVE? I WAS STRUCK BY THE LARGE VARIABILITY AT THE FRONT. AND I HAVEN'T WATCHED A RAT EAT BUT I HAVE WATCHED MY DOG EAT AND I'M KIND OF APPALLED AT HOW SHORT IT IS BETWEEN TASTING AND GULPING. >> SO EACH ANIMAL IS DIFFERENT. WE DON'T PUT ANY TIME RESTRICTIONS ON OUR RATS IN THIS CASE. THE AMOUNT OF TIME IT TAKES WILL DEPEND UPON A LOT OF FACTORS, INCLUDING WHAT THE ACTUAL STIMULUS IS. IF WE RAMP UP THE CONCENTRATION OF THE QUININE, THE ANIMAL WILL GET TO GAPING FASTER. IF WE RAMP IT DOWN, IT WILL TAKE LONGER. ALSO, IF THE AP MALL ANIMAL KNOWS WHAT'S COMING, IT WILL HAPPEN FASTER. IN FACT, ALFREDO, MY FIRST POSTDOC, IS IN THE PROCESS OF TEARING DOWN A BUNCH OF STUFF THAT I HAVE DONE BY SHOWING WHEN YOU PUT THE ANIMAL IN A NOR NATURALISTIC SITUATION APPROACHING FOOD AND IT HAS AN IDEA OF WHAT'S GOING TO OCCUR IN ITS MOUTH, THE GAPE OCCURS FASTER, IN FACT, THE WHOLE PROCESS APPEARS FASTER. AND IF YOU DO SOMETHING -- YOU SET IT UP SO THAT IT KNOWS THAT THERE'S SOMETHING HERE, IT HAS NO IDEA WHAT IT IS, BUT IT MIGHT BE SOMETHING TOTALLY AWFUL, YOU CAN GET THESE THINGS TO HAPPEN VERY FAST. BUT UNDER MOST CIRCUMSTANCES LIKE THIS ONE, IT USUALLY TAKES ABOUT A SECOND, BY THE WAY, IN HUMAN BEING, WE GAPE -- I TOOK AWAY THE PICTURE, BUT HUMAN BABIES GAPE LIKE CRAZY TO NASTY FOODS. SO DO PEOPLE WITH CERTAIN FORMS OF DEMENTIA, AND THOSE GAPES HAPPEN ABOUT ON THE SAME TIME SCALE, TYPICALLY ABOUT A SECOND TO -- >> RELATIVE TO THE AMOUNT OF TIME IT TAKES UNDER NORMAL CONDITIONS WHEN THEY'RE JUST EATING BETWEEN THE TIME THAT THEY TASTE AND SWALLOW, BECAUSE IF THEY DO THAT IN A HALF SECOND -- >> SO AGAIN, UNDER NORMAL CONDITIONS, HUMANS AND DOGS ARE APPROACHING SOMETHING WHERE THEY HAVE A PRETTY GOOD IDEA WHAT'S HAPPENING, IN FACT, YOUR DOG, ONE OF THE THINGS THAT MAKES IT DIFFERENT IS THAT IT'S ALWAYS THE SAME THING. AND SO WHEN YOU HAVE AN IDEA OF WHAT'S HAPPENING, IT'S GOING TO HAPPEN A LITTLE FASTER BUT IF YOU WATCH YOUR DOG CAREFULLY, AND YOU GIVE IT SOMETHING -- A SITUATION WHERE IT DOESN'T EXACTLY KNOW WHAT IT'S GOING TO BE AND IT HAS TO FIGURE IT OUT, YOU'LL SEE THAT PROCESS GOES A LITTLE SLOWER AND THAT THE ANIMAL WILL SWITCH FROM CHEWING, CHEWING, CHEWING, TO THE ACTUAL SWALLOWING SOMETIME BETWEEN A .5 AND 1.5. TRY T GIVE YOUR DOG WHOLE NEW TASTES AND SET IT UP IN A SITUATION WHERE IT CAN NO LONGER TRUST YOU, AND YOU'LL SEE THAT, AND YOU WILL ALSO RUIN YOUR RELATIONSHIP WITH YOUR DOG. >> THANK YOU FOR YOUR TALK. >> THANK YOU. >> IS ANY OF THE VARIABILITY IN THE TIME LATENCY TO GAPE AFFECTED BY WHETHER OR NOT THE ANIMAL HAS ALREADY BEEN FEEDING? IS THAT AFFECTED BY WHAT IT'S BEEN FEEDING PRIOR TO WHETHER OR NOT YOU GIVE IT QUININE OR SUCROSE? >> SO IF ANY OF YOU COULDN'T HEAR, THE QUESTION WAS ABOUT WHETHER OR NOT THE VARIABILITY AND LATENCY OF GAPING COULD BE AFFECTED BUT ESSENTIALLY RECENT EXPERIENCE WITH FOOD THAT THE ANIMAL HAS HAD. HERE AGAIN, WE'RE DOING SOMETHING RIDICULOUSLY EEK LOGICALLY INVALID IN THAT EVERY TRIAL IS ESSENTIALLY RANDOM AND UNPREDICTABLE BY THE ANIMAL. WE'VE ONLY DONE A LITTLE BIT OF THIS, BUT WHEN YOU START GIVING THE ANIMAL PREDICTABILITY, YOU WILL, IN FACT, BY THE SAME KIND OF PROCESSES THAT WE'VE BEEN TALKING ABOUT, TEND TO SPEED THAT UP. YOU'LL ALSO CAUSE MISTAKES WHERE WHETHER YOU SPICH IT SWITCH IT UP -- BASICALLY THE TASTE SYSTEM IS ENDLESSLY FLEXIBLE AND ALL OF THESE FACTORS WILL CHANGE WHAT'S GOING ON. TO BE SURE, I DON'T THINK THAT WHAT WE'VE SHOWN THAT IS INVIOLATE, THAT WILL NEVER CHANGE, IS THE ACTUAL TIMEING. I THINK THE ONE THING THAT'S GOING TO ALWAYS BE THE CASE IS VARIABLE AND WILL MOVE AROUND ALL SORTS OF WAYS, NOT EVEN SURE THAT THE WHOLE THREE PHASES THING IS SOMETHING THAT ALWAYS HAS TO HAPPEN. WHAT I THINK IS IMPORTANT HERE, THAT WE SEE OVER AND OVER AGAIN, AND THAT WE THINK IS KEEPLY TRUTHFUL ABOUT THESE SYSTEMS IS THAT YOU GET A DYNAMIC AND YOU GET A CHANGE FROM ONE STATE TO THE NEXT, AND THOSE CHANGES ARE ESSENTIALLY THE TRANSITIONS IN WHERE THE PROCESSING IS. >> DO YOU HAVE ANY SENSE OF THE STABILITY OF THE CIRCUIT AND ITS MODULATORY FUNCTION OVER DEVELOPMENT? >> A GREAT QUESTION AND I HAVE NO CLUE. WE KNOW THAT A LOT OF -- WHAT DO I KNOW? I'M AFRAID TO SAY SOMETHING AND THEN JUST BE COMPLETELY WRONG. WE KNOW THESE TASTE-RELATED BEHAVIORS EMERGE VERY YOUNG, AND WE KNOW THAT REALLY YOUNG ANIMALS CAN LEARN THE LEARNING TASKS THAT WE SHOWED, BUT WE DO KNOW THAT THE LEARNING TASKS TO WEANING, FOR INSTANCE, IT'S VERY HARD FOR A RAT TO LEARN A NEW PREFERENCE, OR TO SOCIALLY LEARN A NEW PREFERENCE. WE THINK THAT CONDITION TASTE CONVERSION IS SOMETHING THAT HAPPENS YOUNGER BUT WE KNOW VERY LITTLE ABOUT THAT, WHICH IS SHAMEFUL, BUT THERE YOU ARE. >> YOU SHOWED THAT THE RESPONSES IN GUSTATORY CORTEX TYPICALLY PRECEDE THE ONES IN THE OLFACTORY CORE TECH. I'M JUST WONDERING, WHERE DOES THAT DIFFERENCE IN SPEED ARISE FROM, AND IN WHAT WAY IS THAT ADAPTIVE? >> SO IT ISN'T JUST THAT THEY PRECEDE, IT'S WITHOUT THE CORTEX THERE, THEY DON'T EVEN MAKE IT. SO THE FIRST ANSWER; WE THINK THAT THE CIRCUIT -- THE WAY THEY PROCEED IS THAT SOMEHOW YOU GET CORTICAL TO CORTICAL PROCESSING, AGAIN, WE DON'T KNOW HOW MANY SYNAPSES THERE ARE IN THAT, IT'S ACTUALLY MORE DIFFICULT THAN IT SOUNDS TO SAY IN AN AWAKE ANIMAL ANIMAL. AND WE'RE WORKING ON IT. BUT THERE ARE MULTIPLE PATHWAYS BETWEEN THESE TWO STRUCTURES THAT ARE PROBABLY ALL FUNCTIONING. AND CERTAINLY THERE ARE SOME TRIALS WHEN THE LATENCY FROM ONE TO THE OTHER IS PRETTY LARGE. AND SO I DON'T THINK THAT THIS IS SOMETHING THAT'S -- WHERE THIS TRANSMISSION IS HAPPENING ACROSS THE SINGLE SYNAPSE. BUT THAT'S REALLY ALL I'VE GOT FOR YOU RIGHT NOW. BUT WITH REGARD TO THE SIGNIFICANCE OF IT, OH, WOW, WE COULD HAVE LIKE A WHOLE DAY OF DEBATE ABOUT THAT. CERTAINLY I THINK WHAT'S UNDERLYING A LOT OF THIS IS THE FACT THAT AS FAR AS THE FIVE SENSES ARE CONCERNED, AND I KNOW THAT I'M GOING TO MAKE A LOT OF ENEMIES RIGHT NOW, TASTE, I THINK, IS PRIMARY. FOR ONE REASON AND ONE REASON ONLY. WHEN YOU SMELL SOMETHING OR SEE SOMETHING OR HEAR SOMETHING OR EVEN GET TOUCHED BY SOMETHING, IT IS EXTERNAL TO YOU. WHEN YOU TASTE SOMETHING, IT IS ALREADY IN YOUR BODY AND IT SOMETHING THAT IS EITHER GOING TO NOURISH YOU OR KILL YOU. OR HARM YOU. AND SO WHEN YOU TASTE SOMETHING, THERE IS A CERTAIN AMOUNT OF URGENCY THAT WE THINK IS FAIRLY SPECIAL, IN FACT, WE WOULD ARGUE THAT A LOT OF WHAT MOST ANIMALS DO IN THEIR DAILY LIFE IS FIGURE OUT WHAT STIMULI ARE THINGS THEY WANT TO GET INTO THEIR MOUTHS. SO WE THINK THAT WHAT'S UNDERLYING A LOT OF THIS HERE IS THE NEED FOR THAT ASSOCIATION. THE FACT THAT PART OF WHAT AN ANIMAL -- BASE UK THINGS AN AL MALL DOES IS LEARNING TO ASSOCIATE DISTAL QUEUES TO THE TASTE WHICH, AGAIN, TO BE FAIR, IF MY FRIEND WAS HERE, HE'D SAY IT'S ALL SECONDARY TO WHAT'S GOING ON IN THE GUT, A TASTE ASSOCIATED WITH HOW IT MAKES HIM FEEL POST SUGGESTIVELY, BUT THESE CONNECTIONS AND THE IMPORTANCE OF TASTE CORTEX IN ALL THESE PROCESSES HAS TO DO WITH THE FACT THAT A LOT OF WHAT THE ANIMAL HAS TO DO IN REAL LIFE IS LEARN WHAT STUM LIE WHAT STIMULI A RE GOING TO TASTE GOOD. BUT A LOT IS SPECULATION. ALL RIGHT. THANK YOU VERY MUCH.