>> GOOD MORNING. IT'S A PLEASURE TO INTRODUCE TODAY'S SPEAKER, STEN GRILLNER. I FIRST DID NOT MEET STEN GRILLNER WHEN I WAS CHAIR OF THE PROGRAM COMMITTEE OF THE SOCIETY FOR NEUROSCIENCE AND TOM SMITH FROM NEUROLOGY CALLED ME AFTER THE PROGRAM WAS PUBLISHED AND SAID, STARTED OFF BY SAYING SOMETHING LIKE, HOW IS YOUR EVOLUTIONARY KNOWLEDGE? AND HE EXPLAINED THAT IN THE PROGRAM, THE LAMP RAY WAS GROUPED AS IN THE INVERTEBRATE MOTOR CONTROL. SO I WAS HAPPY THAT I WAS AT A GREAT DISTANCE FROM STEN. STEN HAD GOT HIS DEGREE IN 1969 M. D. AND Ph.D. FROM THE UNIVERSITY OF ROTOR BURG, HE THEN MOVED STOCKHOLM, TO THE KAROLISKA INSTITUTE AND THEN TO THE NOBEL INSTITUTE OF PHYSIOLOGY WHERE HE'S CURRENLY PROFESSOR AND DIRECTOR. HE'S BEEN PRESIDENT OF THE EUROPEAN SOCIETY FOR NEUROSCIENCE, THE FINS, THE EUROPEAN FEDERATION AND HE'S CURRENT LITE SECRETARY GENERAL OF EBRO. NOW HIS WORK HAS BEEN WIDELY RECOGNIZED IN SWEDEN, HE'S RECOGNIZED BY A MEMBERSHIP IN THE ROYAL SWEDISH ACADEMY BUT IN THE UNITED STATES HE'S RECOGNIZED BY THREE DISTINGUISHED ACADEMY, ACADEMY OF ARTS AND SCIENCES, THE NATIONAL ACADEMY OF SCIENCES AND THE INSTITUTE OF MEDICINE OF THE NATIONAL ACADEMY. SO, YOU KNOW WHERE YOUR TRUE POPULARITY LIES. AND I SHOULD SAY, HE WAS AMONG THE FIRST WINNERS OF THE COBBLEY PRIZE. STEN'S RESEARCH GOALS HAVE BEEN TO UNDERSTAND THE INTRINSIC FUNCTIONS OF NEURONAL NETWORKS FOR THE GUIDANCE OF LOCOMOTION AND POSTEUR AND THE GOAL IS TO EXTEND THIS KNOWLEDGE FROM I. N. CHANNELS TO BEHAVIOR. HE WORKED ON A SIMPLE RELATIVELY SIMPLE SYSTEM TO STUDY THIS. THE VERTEBRATE, A LAMP RAY AND HE'S USED TO THIS TO EXPLORE FUNDAMENTAL ORGANIZATIONAL FEATURES OF THE MOTOR SYSTEM. AND THAT'S WHAT HE'S GOING TO TALK ABOUT TODAY, THE VERTEBRATE BLUEPRINT OF THE MOTOR SYSTEM FROM FOREBRAIN TO SPINAL CORD. STEN IT'S A GREAT PLEASURE TO HAVE YOU. >> THANK YOU, BOB FOR IT IS KIND INTRODUCTION AND FOR INVITING ME TO NIH. IT'S A GREAT PLEASURE TO BE HERE GONE. WE HAVE VISITED NOW AND THEN OVER THE YEARS. SO I WILL NOW TALK ABOUT THE BLUEPRINT. BUT FIRST, THE ABOUT MOTOR PROGRAMS IN GENERAL AND HOW THEY ARE CONTROLLED AND SELECTED FOR THE LITTLE NEW BORN CREATURE IS SWEET LITTLE SURVIVAL MACHINE. IT HAS A VERY LIMITED BEHAVIOR REPERTOIRE, IT CAN BE FED, IT CAN CRY FOR HELP, IT CAN BREATHE, VERY IMPORTANT AND CRY FOR HELP AND SO FORTH, BUT NOT MUCH MORE. DURING THE NEXT YEAR HAVE YOU A GRADUAL DEVELOPMENT IS THE CHILD CAN RAISE THE HEADS, STEN WITH SUPPORT, CRAWL, AND FINALLY AFTER ABOUT A YEAR, STAND AND MAINTAIN POSTEUR AND ALSO WALK. ONCE THE CHILD LEARNS TO WALK BUT IN REALITY, IT'S VERY MUCH A MATURATION OF THE NERVOUS SYSTEM. IF YOU HAVE TWO IDENTICAL TWINS AND TRAIN ONE, THE TRAINED ONE WILL START IN THE MORNING AND THE UNTRAINED ONE IN THE AFTERNOON, SO IT'S REALLY VERY MUCH WITH REGARD TO THIS TYPE OF MOTOR PATTERNS AND INNATE. AND OF COURSE, YOU CAN SAY THAT THE WALKING MOVEMENTS OF HUMANS WOULD SEEM QUITE DIFFERENT BUT LIKE WE NEED THE RECENT REPORT THAT THE DETAIL STUDY OF THE MOTOR PATTERNS OF THE--OF THE HUMAN WALKING AND THE RHESUS MONK SCHEOTHER MAMMALS AND ALSO SIMILAR, THE WALKING PATTERNS OF THE GUINEA FOUL WHICH MAKE ITS THE--GUINEA FOWL WHICH MAKE ITS THE ESSENTIAL CONTROL HERE IS DEVELOPED AT LEAST AMONG REPTILES. THE MOVEMENT IS CONTROLLED TO LARGE DEGREE BY PREFORM NETWORKS, ADAPTABLE NETWORKS, NETWORKS IN THE SPINAL CORD AND LOCOMOTION AND HAVE YOU NETWORKS IN THE BRAIN STEM AND FOREBRAIN. SO ESSENTIALLY, WHEN YOU ACTIVATE THIS NETWORK IN THE SPINAL CORD FROM THE BRAIN STEM, IT WOULD BE IN THE WALKING MOVEMENT IF YOU ARE OFFICIAL OR THE LAMP RAY, YOU WILL START SWIMMING. IF YOU--IN THE BRAIN STEM, YOU HAVE THE PATTERN FOR BREATHING AND WHICH IS ON THROUGHOUT LIFE. YOU HAVE THE CHEWING AND YOU CAN SEE WHAT BEHAVIOR YOU WILL EXPRESS AND A LITTLE BIT MORE COMPLICATED IN THE SUPERIOR COLLICULUS, THIS IS A BIT MORE FOR THE EYE MOVEMENTS AND ESSENTIALLY WHEN YOU ACTIVATE THE SUBGROUP OF NEURONS HERE, YOU WILL ENERATE THE EYE MOVEMENT WITH A CERTAIN DIRECTION, THIS IS MORE COMPLEX LIKE A MOTOR MAP AND LINKED TO THE EYE MOVEMENT AND IT'S MORE ORCREPTING MOVEMENTS. --ORIENTS MOVEMENTS. YOU HAVE OTHER TYPES OF MOVEMENTS THAT ARE CONTROLLED FOR INSTANCE, THE EXPRESSION OF EMOTIONS. HUMANS HAVE ABOUT SEVEN DISTINCT EXPRESSION OF EMOTIONS, LIKE THIS GUY, DISPLAY ANGER, BUT YOU ALSO CAN CRY--YOU CAN CRY FOR HELP, CAN YOU SMILE, CAN YOU LAUGH, CAN YOU LOOK FOR IT, ET CETERA. AND THESE ARE DISTINCT MOTOR PATTERNS AND THEY ARE NOT LEARNED EITHER. SO ESSENTIALLY HAVE YOU THIS RANGE FROM VERY SIMPLE PROTECTIVE RESOURCES THAT WE'RE SWALLOWING, RESPIRATION, POTTURE, CHEWING, EXPRESSION OF EMOTIONS, MOTOR, REACHING, ALSO. AND YOU HAVE MANY MORE CPG,s MOTOR PATTERN GENERATORS. DOES EVERYBODY HEAR ME? GOOD. SO HAVING ALL THESE DIFFERENT NETWORKS AVAILABLE, YOU NEED ALSO TO HAVE THE THAT DECIDES WHETHER CPTs ARE ALLOWED TO BE TURNED ON THAT CONTROL WHETHER THEY CAN BE AN ACTION OR NOT AND THERE IS A BASAL GANGLIA WHICH I WILL TALK ABOUT AND ALSO FOR SOME VALUE BASED DECISIONS OF IMPORTANCE. AND--BUT THEN FIRST SEE, THE GENERAL DESIGN OF ONE OF THE SYSTEM AND THAT WE WILL TAKE THE LOOK OF THE CPTs, THERE. AND ESSENTIALLY, YOU HAVE IN ALL MAMMALS, ALL VERTEBRATES, HAVE YOU CPGs IN SPINAL CORD AT CENTRAL PATTERN NETWORK THAT CAN ACTIVATE THE APPROPRIATE MUSCLES IN THE APPROPRIATE SEQUENCE. YOU OF COURSE THEN HAVE THE CENTER INPUT GOING BACK THAT HELPS COORDINATE THE MOVEMENTS. THE CPTs ARE TURNED ON FROM THE BRAIN STEM BY LOCOMOTOR COMMAND REGIONS, AGAIN, PRESERVED SO CAN YOU AGAIN STIMULATE THAT REGION AND THEY WILL START SWIMMING AND THE MORE YOU START, WITH A SWIM, IN THE BURDENS, TELL START, IT WILL START WALKING AND THEN WITH HIGHER STRENGTHS, MORE NEURONS, IT WILL START FLAPPING IN THE WINGS AND IN THE MAMMOTH, YOU CAN GO FROM WALKING TO TROT TO GALLOP. SO IT'S A VERY CONVENIENT WAY OF HAVING A TONIC ACTIVATION OF THIS REGION, ACTIVATING THE NETWORK IN THE SPINAL CORD THAT ARE BASICALLY RESPONSIBLE FOR THE BASIC COORDINATION. THIS IS--IN A SENSE POSITIVE SYNERGY. BUT TO MAKE THAT MEANINGFUL, YOU NEED TO HAVE STEERING MOVEMENTSMENTS AND THEN TAKE THEM, PLAY MAJOR ROLES UP HERE, AND YOU NEED TO MAINTAIN POSTEUR, CONTROL OF AUDIO ORIENTATION DURING THE MOVEMENT, WHEN YOU HAVE ALL THIS, YOU CAN DIRECT THE MOVEMENTS, MAINTAIN THAT SUCCESSFULLY, BUT THEN ALSO HAVE YOU NEED TO HAVE SOMETHING THAT DECIDE WHEN IS A GIVEN MOTOR PROGRAM SHOULD BE ON AND AT LEAST AN IMPORTANT ROLE IN THIS CONTEXT PLACES THE BASAL GANGLIA, AND WE TALK ABOUT THE BASAL GANGLIA AND THE CORTICAL CONTROL AND THE LAMP RAYS OF COURSE NOT THE CORTEXT BUT CALLED IT. I COULD HAVE TALKED ABOUT THESE PARTS BUT I WOULD CHOOSE THEN TO FOCUS ON THESE PARTS OF SAYING THAT THESE ARE NOT EQUALLY IMPORTANT. SO IF ONE LOOKS ABOUT VERY SIMPLISTIC DESCRIPTION OF THE MOTOR PROGRAMS FOR WHAT THIS REFERRED TO AS A DIARY PATHWAY, YOU HAVE THE OUTPUT OF THE BASAL GANGLIA AND THEN AGAIN TONICALLY ACTIVE GABAergic VIEWS THAT ADDRESS AT THE HIGH RATE AND THEN HAVE YOU DIFFERENT PARTS OF THE OUTPUT NEURONS THAT PROJECT TO THE CENTERS FOR CONTROL LOCOMOTION, CONTROL POSTURE OF COURSE THE SACCADIC EYE MOVEMENTS AS COLLEAGUES HAVE PILOT PIONEERED MANY YEARS AGO. AND I LIKE TO EMPHASIZE THAT THE LARGE PART OF THE BASAL GANGLIA ACTIVELY GOES DIRECTLY TO THE BRAIN STEM. THEN, MAYBE EVEN 50% OF THE INNOVATION, YOU WOULD THEN OF COURSE HAVE THE INPUT OF THE HYPOTHALAMUS THAT FITS BACK TO CORTEX THAT RECEIVES MUCH RECOGNITION IN THIS CONTEXT. IT'S IMPORTANT TO REALIZE THAT IT'S NOT THE WHOLE STORY. YOU THEN HAVE THE NEURONS IN STRIATUM THAT PREDETECTED DIRECTLY HERE--PREDICT DIRECTLY HERE. THEY ARE IN THE INWARD SYSTEM, AT THE HYPER POLARIZEDARRIZED LEVEL AND DIFFICULT TO ACTIVATE IN CONTRAST OF THESE GUYS THAT FIRE AUTOMATICALLY AND WITH YOUR BRAIN NOW WITH 30 OR 40-HERTZ PERHAPS. AND ANOTHER ASPECT HERE THAT THALAMIC INPUT TO TRIAT UMKC IS ALMOST 50% OF THE INPUT EQUALED, NOT QUITE WITH THE INPUT FROM CORTEX TO STRIATUM. AND IT'S AGAIN IMPORTANT TO REALIZE BECAUSE PRACTICALLY ALL THE EFFORT IS ON THIS PART. IF YOU SHOULD GENERATE LOCOMOTOR MOVEMENTS FOR INSTANCE BUT THEN ANTICIPATE THAT YOU WILL HAVE TO ACTIVATE SUBPOPULATIONS, SOME SENSE HERE WHICH WOULD INHIBIT THESE AND REMOVING INHIBITION AND THE LAB MOTION. WE OF COURSE THEN HAVE A VERY--ANOTHER VERY IMPORTANT PLAYER WHICH IS THE DOPAMINE INPUT TO STRIATUM AND THAT SETS THE RESPONSIVENESS OF STRIATUM, IT'S TOO LITTLE, IT'S DIFFICULT BETWEEN THE SHADE, TOO MUCH AND YOU GET INVOLUNTARY HYPER KENESIS, THAT'S VERY SIMPLIFIED. IN REALITY, IT'S MORE COMPLEX. SO STRIATUM CONTAINS PROJECTION NEURONS AND PART OF THESE ROUGH ATOM GEEKS NEURONS HAVE E-ONE RECEPTORS AND DOPAMINES AND THIS IS THE TRANSACT PATHWAY IN WHICH I TALKED ABOUT--DIRECT PATHWAY IN WHICH I TALKED ABOUT HERE AND THEN WE HAVE WHAT'S REFERRED TO AS INDIRECT PATHWAY AND THIS DIFFERENT SET OF NEURONS WITH THE TWO RECEPTORS ARE INHIBITED AND THE EFFECT OF THIS PATHWAY SHOULD BE TO ENHANCE THE INHIBITORY ACTIVITY AND THEN KD--SALLY WHA. SO IN A MALLALLIAN PERSPECTIVE IS WHAT HAPPENS NOW? CAN YOU AT ALL PERFORM DIRECTED BEHAVIOR IF YOU HAVE THE CORTEX, IF YOU HAVE THE THALAMUS, HAVE YOU STRAIGHT? AND ACTUALLY YOU CAN EXPERIMENT ON CAT, WE'RE--AND RABBITS AND RODENTS AND SO FORTH OVER MANY YEARS FROM THE 60S AND 70S SHOWED THAT AS THIS CAT IN WHICH NEOCORTEX WAS OPERATED, FOUR OR FIVE WEEKS, AND THIS CAT WAS IN SORT OF PUT IN A CAGE HERE TRYING TO FIND ITSELF WAY DOWN MOVING IN THE QUIET RADIATED WAY BUT IT CAN ALSO, WHEN YOU--SEE A CAT LIKE THAT, IT MOVES OVER THE FLOOR LOOKING VERY MUCH LIKE ORDINARY MOVEMENTS. AND IT CAN BE GET--SEEMINGLY GET HUNGRY TRYING TO FIND FOOD AND IDENTIFY WHERE THE FOOD IS, START EATING OR SEARCHING. IT'S A GOAL-DIRECTED ASPECT AND EVEN MORE IT CAN BE TAUGHT TO REMEMBER THE LOCATION FOR THE IT, THE ALSO THE WORK OF THESE ORDERS, THEY CAN FIND A WAY OUT OF A COMPLEX MAZE. AND IT CAN, IF YOU HAVE IT IN A CNY OF OTHER CATS, IT WILL HAVE DIFFICULTY INTERPRETING THE OTHER CATS WITH THE RESPONSE BY ATTACKING AND IT IS QUITE EFFICIENT IN ATTACKING. THEN SO THE OTHER CATS IN THE COLONY LEARN TO AVOID THIS GUY. SO IT'S ALSO A FAIRLY ELABORATE MOTOR BEHAVIOR. SO THE CONCLUSION THERE IS THAT VERY LARGE PART OF THE NEUROMACHINE, GOAL DIRECTED BEHAVIOR, IS AVAILABLE--CORTICAL, BUT OF COURSE, NORMALLY DEPENDENT ON INPUT FROM CORTEX AND THAT THE FACT IS THAT A LOT OF THE BEHAVIOR REPERTOIRE CAN BE HANDLED AT THE SUBCORTICAL LEVEL BUT BE MODULATED AT THE CORTICAL LEVEL. ANYHOW, THIS IS A FUNCTION OF HAVING THE BASAL GANGLIA WITH THE THALAMIC INPUT INTACT BECAUSE IF YOU REMOVE THE FOREBRAIN, THEN HAVE YOU THE--YOU CAN SEE THE DIFFERENT TYPES OF MOVEMENT BUT THEY'RE NOT ALL GOAL-DIRECTED. SO THAT'S A BIT OF THE BACKGROUND. SO WHAT WE DID THEN FROM OUR EARLY WORK ON MAMMALS, WE WENT OVER TO THIS ANIMALS THAT SEEM LIKE INVERTEBRATES AND SO, WE--WE CHANGED OVER TO THE LAMP RAY, ESSENTIALLY, NORMALLY, YOU WOULD MOST OF US WORK ON RODENTS, SOMETIMES PRIMATES, TRYING TO EXTRAPOLATE TO THIS FELLOW, MORE OCCASIONALLY TO FUNCTIONS, THIS IS RELEVANT FOR THIS FELLOW. BUT SINCE MUCH OF THE NERVOUS SYSTEM IS IN PRINCIPLE BUILT IN THE SIMILAR WAY. WE--I CHOOSE MANY YEARS AGO, WHEN TRYING TO UNDERSTAND THE CPD FROM THE CAT THAT I NEEDED A VERY SIMPLE MODEL AND I WENT TO A SIMPLER VERTEBRATE THAT'S POSSIBLE WHICH IS THE LAMP RAY AND TRY AND EXTRAPOLATE TO THIS. AND THIS IS THE LAMP RAY. IT HAS THE FIRST VERTEBRATE GROUP APPEAR, FROM THE LINE QUITE SOMETIME AGO AND IT HAS DEVELOPED ALL BASIC FEATURES OF THE VERTEBRATE NERVOUS SYSTEM SO THAT'S WHY WE--WHY WE SPENT MUCH TIME WITH THE HISPANIC CODE IN THE BRAIN STEM BUT NOW WE HAVE ALSO ADDRESSED THE QUESTION, IS FROM A BASAL GANGLIA AND IF SO, HOW DOES IT CONTRIBUTE TO THE CONTROL OR MOVEMENT. AND THE REASON TO DO THAT IS THAT THE LAMP RAY CONFRONTS RODENTS OR PRIMATES HAS A LIMITED REPERTOIRE, SO IT'S EASIER TO LINK IT IS HEAVY FUNCTION. HAVE YOU COMPARATIVE NEURONS BUT MUCH TOO MANY. AND YOU HAVE--WE HAVE VERY DETAIL KNOWLEDGE OF DOWN STREAM MOTOR CIRCUITS FOR LOCOMOTION, BODY ORIENTATION AND EYE-ORIENTS MOVEMENTS. IT'S THE FIRST VERTEBRATE GROUP TO APPEAR AND LEFT FROM THE BLIND, 560 MILLION YEARS AGO, IT MEANS WHAT WE HAVE IN COMMON SHOULD BE DEVELOPED AT THAT POINT. SO FIRST I WILL LOOK NOW ON THE DIFFERENT COMPONENTS OF THE BASAL GANGLIA AND WE FIRST LOOK STRAIGHT AND THERE IS STRIATUM, IT IS LOCATED HERE, IT RESPONDS TO CORTEX, AND IF YOU LOOK AT THE INPUT TO STRIATUM, IT HAS DOPAMINE NEURONS, HISTA MINE NEURONS FROM BOTH THALAMUS AND FROM PATIO. SO IT HAS THE SAME TYPE INPUT. IT HAS THE SPAN AND PREDICION NEURONS, LIKE IN A SENSE LIKE THE MEDIUM SPINE. IF YOU LOOK AT THE DIFFERENT NEURONAL TYPES EXPRESSED, WE HAVE, THEY ARE GABBERERGIC AND WE HAVE ALCOHOLINERGIC INNOVATION AND TWO SUBSETS OF PREDICTION NEURONS, ONE WITH THE ONE RECEPTOR AND TWO WITH THE TWO RECEPTOR AND AND WE GIVE EVIDENCE FOR THAT AND THEN WE HAVE SOME DIFFERENT OTHER MARKERS. SO IF YOU LOOK ON THE DOPAMINE TRANSMISSION, WE HAVE--AND THE ONE RECEPTORS AND IF WE ARE RECORDING FROM NEURONS WITH THE ONE RECEPTORS, AND APPLIED THE ONE AGONIST AND THE ONE RECEPTOR DOES THE SAME THING IN MAMMALS, IT EXCITES THE NEURONS. IF WE LOOK FROM NEURONS WITH THE NEURONS THAT HAVE THE TWO RECEPTORS, WE HAVE REPRESSION OF ACTIVITY. SO IT'S THE SAME TYPE OF ORGANIZATION AND WE ALL HAVE SIMILAR TYPE OF SYNAPSIS ALSO WITH THE HD TERMINALS SO WITH REGARD TO MORPHOLOGY AND PREGEEKS NEURONS, THE SITUATION IS SIMILAR. IF WE THEN ASK, DOPAMINE INNERVATION HAVE THE SAME, THE SAME RODE, SO, AND WE FOUND THAT AT LEAST HYPER KINESIA, ESSENTIALLY IF YOU GIVE MTPTP, IT CAN GET DOWN TO FIVE% OR SO. THEN YOU'LL GET HYPER KINETIC SYMPTOMS. THEY ARE--THE LAMP RAYS DON'T INITIATE SWIMMING. IF YOU--CAN YOU STILL PUSH THEM TO SWIM, THEY HAVE SOME SORT OF RIGIDITY, THEY HAVE A DELAYED RESPONSE TIME OR SYMPTOMS OF MARKIN SON'S, OF COURSE MPTP IS A DIRTY DRUG SO YOU COULD IMAGINE HAVE YOU OTHER EFFECT. BUT IF YOU UNDER THESE CONDITIONS GAVE APOMORPHINE, CAN YOU RECOVER. SO ESSENTIALLY DOPAMINE INNERVATION HAVE THE SAME TYPE OF EFFECTS IN THIS OLD CREATURE. AND SO IF YOU LOOKOT CELLS, AND YOU PATCH THEM, ONE HALLMARK OF THESE NEURONS HAVE BEEN THAT THEY HAVE INWARD, POTASSIUM INWARD RECTIFIER CHANNELS, WHICH ARE CHANNELS THAT ARE OPEN AT THE HYPER POLARIZED LEVEL AND MAINTAIN THE CELLS IN THE HYPER POLARIZED LEVEL. BUT WHEN YOU DEPOLARIZE YOUR CLOSEST CHANNELS AND THEN IT'S EASIER TO ELICIT EXCITATION AND HERE YOU CAN SEE THAT THIS IS A HALLMARK WITH CURRENT INJECTIONS OF THE EXCITABILITY. SO THIS MEANS ESSENTIALLY THAT MORE CURRENT IS REQUIRED TO INJECT HERE RATHER THAN HERE. SO THAT IS OUR--THEY ALSO HAVE THIS INWARD RECTIFIED PROPERTIES. THEY HAVE THE TWO PRO DICTIONS THEW ARE GABBERERGIC AND THEY HAVE THESE FOR THE GABBA AND THE ENKEPH ALIN. AND THE AND DARPP IS DISCOVERED IN RODENTS AND THIS LEADS TO HYPER KINESIA, INWARD RECTIFYS BUT NOT--NOT SHOW YOU THAT THE PROPERTIES OF THE SYNAPTIC IBT--INTEGRATE PUT EXCITE ATORY INPUT FROM THE THALAMUS, DEPRESSING SYNAPSES AND FROM CORTEX IS FACILITATING AND THAT'S ALSO SIMILAR BECAUSE IT REPORTED A FEW YEARS AGO, I THINK THAT THIS ACTUALLY OCCURS IN RODENTS. SO EVEN TO THAT LEVEL, WE HAVE THIS EFFECT. ESSENTIALLY ONE CAN SAY THIS IS THE STRIATUANDATUS STRUCTURE HAS BEEN CONSERVED THROUGHOUT VERTEBRATE EVOLUTION. NOW WHAT ABOUT THE REMAINING THOUGHT? IT'S OUR BASAL GANGLIA OUTPUT STAGE, IT'S ALSO DIRECT PATHWAY. WE IDENTIFIED THEM SOME YEARS AGO, THAT WE HAVE GABAergic PROJECTION NEURONS GO INTO A DIFFERENT MOTOR CENTERS IN THE BRAIN STEM AND BACK TO THALAMUS AND THESE NEURONS HAVE INPUT FROM STRIATUM. AND IF YOU RECORD FROM THEM, THEY ARE TONICALLY ACTIVE AND IT'S NOT DRIVEN BY GLUTEA MITTERGIC INPUT BECAUSE IF YOU BLOCK GLUTEA MATE YOU STILL RETAIN THE SAME LEVEL OF ACTIVITY. SO THAT'S AGAIN, THAT'S THE HALLMARK OF THE OUTPUT LEVEL. ANOTHER IMPORTANT FACTOR IS THAT THE PROJECTION NEURON FIST THEY ARE TO CONTROL HELP, HELP CONTROL DIFFERENT PATTERNS OF BEHAVIOR, YOU NEED OF COURSE HAVE DIFFERENT OUTPUT GROUPS FROM PATTERNS AND YOU DO INDEED HAVE THE NEURONS THAT PROJECT TO THE COMMAND REGION OR SEPARATE FROM THOSE THAT PREDICT INTO THE DISCIPLINARY INSEVERE MITRAL LIDDIC MOTORS, SO IT'S SPECIFICITY, THAT'S WHAT THEY ALLOW FOR CONTROL EVER--OF DIFFERENT. THE NEXT QUESTION IS IF YOU NOW HAVE THESE PROJECTIONS IS THIS SELECTIVE ON TO--FROM THE DONE. TYPE AND WHICH WOULD BE REQUIRED IN THE DIRECT PATHWAY. SO HERE WE HAVE A NEURON THAT IS RETROGRADELY STAINED FROM THE OPTIC TECT OPEN, IT PROJECTS DIRECTORY OUT ON PART OF THE DIRECT PATHWAY. AND IF YOU THEN LOOK ON SUBSTANCE P HERE WITH A POSITION, YOU HAVE CLOSER POSITIONS FROM SUBSTANCE P, AND PRACTICALLY NO FROM ENKEPH ALIN, WHICH IS RED HERE. SO IT MEPS THERE IS A SELECTIVE INPUT FROM THE D-ONE PROJECTS NEURONS TO THE OUTPUT NEURONS AND ESSENTIALLY, A DIRECT PATHWAY. SO YOU HAVE--I HAVEN'T SHOWN YOU THIS BUT IT'S WELL PUBLISHED. SO IF YOU HAVE THE OUTPUT STAGE, THEY ARE GABAergic, THEY ARE TONICALLY ACTIVE AND YOU HAVE A DIRECT INPUT FROM THE DONE. SO IT'S ALL ASPECTS OF THE DIRECT PATHWAY. THEN COMES THE QUESTION, AND WHEN I STARTED THIS, I HAD RATHER ANTICIPATED THAT THE BASAL GANGLIA WITH WOULD HAVE A DIRECT PATHWAY, FOR THIS WORKING HYPOTHESIS, BUT I DID NOT ANTICIPATE THAT I--THERE WOULD BE AN INDIRECT PATHWAY AND I WANT TO SHOW YOU THIS. SO WHAT WE SHOW YOU NOW IS IT WAS REG STRAIGHT HERE FROM THE D-ONE PRODICTIONS GOING TO THE OUTPUT STAGE. AND THEN WE HAVE THIS PATHWAY. THIS IS ALSO PRESCRIBING ENTER HERE. --PRESENT HERE. AND THIS IS SHOWING A NEURON AND IN THIS PATTERN THAT WAS STAINED FROM THE SUBTHALAMIC NUCLEUS AND YOU CAN SEE HERE THAT YOU HAVE CLOSE UP POSITIONS OF ENKEPH ALIN ON TO THESE NEURONS. SO IT'S--SO IT MEANS THAT THERE ARE CLOSE UP POSITIONS IN THIS CASE, NOT FROM THE D-ONE, BUT FROM THE D-TWO BECAUSE D-TWO WITH THE ENKEPH ALIN GOES TOGETHER. SO THE FIRST PART OF SELECTIVITY OF PREDICTION NEURONS THAT ARE INVOLVED IN THE TECH THERE. NOW IF YOU THEN LOOK ON THE SUBTHALAMIC NUCLEUS WHICH IS LOCATED HERE, IT CAN BE RETROGRADE NEUROBSESSIVES HERE CAN BE RETROGRADED STAINED FROM THE GLOBEUS PATTERNUS AND YOU CAN SEE YOU HAVE NEURONS HERE AND YOU CAN SHOW THE GLUTEA MITTERGIC AND NOT GABAergic SO THESE ARE NEURONS THAT THEY'RE PRO DICKING BACK FROM SUBTHALAMIC NUCLEUS TO THE THALAMUS AND IF YOU RECORD THESE NEURONS THEY'RE SPONTANEOUSLY ACTIVE, MORE IRRADDIC, MORE IRREGULAR, BUT YOU HAVE RHYTHMIC ACTIVITY. YOU HAVE A POST INHIBITORY BOUND WITH IH CURRENT AND THIS IS MOST TYPICAL FOR THE MAMMALIAN FOR THE RODENT SUBTHALAMIC NUCLEUS. SO ESSENTIALLY, IT SEEMS THAT WE HAVE NOT ONLY THE DIRECT, BUT ALSO THE INDIRECT PATHWAY. WITH THE DIFFERENT PROJECTION, SO THIS IS QUITE ELABORATE IN GREAT DETAIL WITH CELLULAR PROPERTIES, ION CHANNELS EXPRESSED, APPETITE EXPRESSED, AVAILABILITY, HERE. SO THEN THE NEXT QUESTION, WE KNOW THEN THAT THERE ARE TONIC ACTIVITY IN THE OUTPUT STAGE PREDICTING ON TO THE MOTOR CENTERS, BUT IF IT'S--IS IT POSSIBLE TO RELEASE ACTIVITY BY REMOVING THIS INHIBITION. SO THIS IS--THIS IS AMBITION OF SUFFICIENT TO INITIATE LOCOMOTION BUT I THINK IT VARIES BUT, THIS--THIS IS A LINE YOU HAVE STRIATUM PATTERN, THE COMMAND REGION SPINEUS AND THE SPINAL CORD, AND IF YOU INJECT GABBA ANTAGONIST HERE, IT WOULD REMOVE THE EFFECT OF THE TONIC ACTIVITY HERE AND YOU WOULD DISINHIBIT [INDISCERNIBLE] AND WHEN YOU DO THAT, CAN YOU GENERATE ALTERNATING LOCOMOTOR ACTIVITY AND WHEN YOU HAVE A INTACT PREPARATION, CAN YOU SHOW THE LOCOMOTION. SO IN THISICATION, IT RELEASES LOCOMOTOR ACTIVITY AND IF YOU DO THIS--CORRESPONDING THING WITH REGARD TO THE SUPERIOR [INDISCERNIBLE], YOU CANI LIAISONSITY EYE MOVEMENT AND HAVE A LOW THRESHOLD FOR EYE MOVE AMS AT [INDISCERNIBLE]. SAME MECHANISM. AND WELL, THIS JUST SHOWS THAT THE GREAT STIMULATION CAN--CAN HERE. CAN VIA INHIBITION OF P A LLIDUM CAN RELEASE LOCOMOTOR ACTIVITY. WHEN YOU RECORD FROM THE SPINAL NEURONS THAT THE MARKEDLY DEMOLARRIZED WITH THE LOCOMOTOR ACTIVITY AND YOU CAN BEGIN ALTERINATION. SO TO TAKE THE CONCEPTION MODEL THAT WE HAVE OF THE LAMP RAY CONTROL SYSTEM IS THAT YOU--THAT WE HAVE MODULES THAT WOULD CONTAIN BOTH THE DIRECT AND THE INDIRECT PATHWAY, THAT ARE SET TO CONTROL LOCOMOTION AND EYE MOVEMENTS, DIFFERENT SETS OF EYE MOVEMENTS, STEERING MOVEMENTS, FEEDING MOVEMENTS AND SO FORTH. AND WHETHER THE MODEL IS ACTIVATED OR NOT, DEPENDS ON THE COMBINED INPUT FROM CORTEX AND THALAMUS AND THE RESPONSIVENESS OF THE MODULE IS DEPENDENTOT LEVEL OF DOPAMINE ACTIVITY, WITH THE DOPAMINE TOO MUCH AND YOU HAVE TYPIER KINEESIS, SO IT'S OBVIOUSLY A SIMPLIFIED DIAGRAM, BUT ESSENTIALLY, ACTIVATING THE DONE, THE DIRECTS PATHWAY WOULD THEN PROMOTE LOCOMOTION AND WHY WOULD YOU HAVE AN EVENTOT INDIRECT PATHWAY. THAT ALSO--I MEAN IT HAS BEEN SHOWN RECENT BY COLLEAGUES AND OTHERS THAT YOU USUALLY HAVE A CO ACTIVATION OF BOTH AND WHEN YOU ELICIT MOVEMENT, YOU NEED TO SUPPRESS MOVEMENTS THAT ARE COMPETING, YOU CANNOT TURN LEFT AND RIGHT AT THE SAME TIME. THIS IS WHY WE ARE STANDING AND I MEAN THIS CONFORMS VERY MUCH TO WHAT [INDISCERNIBLE] DESCRIBED FOR SIGNIFY--SIR CADIC EYE MOVEMENTS. SO WHAT'S HAPPENING IS THAT IT SEEMS THEN THAT THIS CIRCUIT HAS BEEN KEPT AND HAS NOT BEEN MODIFIED SIGNIFICANTLY. WHAT HAS PROBABLY HAPPENED IS THAT YOU HAVE INSTEAD ADDED MODULES, GRADUALLY TO CONTROL PROGRESSIVELY MORE COMPLEX PATTERNS OF BEHAVIOR, BUT YOU HAVE RETAINED THE BASIC CIRCUITRY. IT'S A LITTLE BIT LIKE IF YOU THINK ABOUT THE CEREBRAL CORTEX AND YOU HAVE MORE COT COLORADO UMKCS IN THE SAME WAY CAN YOU IMAGINE THAT HAVE YOU THAT'S MULTIPLYING THE NUMBER OF CIRCUITS. SO AFTERWARDS THIS HAS BEEN CONSERVED FROM THE PRIMATES, THEY AROSE IN CIRCUITS BEFORE TO CONTROL BASIC PATTERNS OF LIKE LOCOMOTION AND FEEDING AND DURING EVOLUTION THESE SEEM TO BE HIJACKED TO DEFINE MOTORS LIKE FINGER MOVEMENT AND DIFFERENT COGNITIVE FUNCTIONS AND LOTS OF NICE EVIDENCE FOR THAT. SO THAT WAS A BASIC CIRCUITRY. THEN WHAT ABOUT THE DOPAMINE NEURONS? WE--WHAT I'VE SAID SO FAR IS THE TONIC DOPAMINE LEVELS SETS THE RESPONSIVENESS OF THIS NEURONS. WE THEN HAVE ALSO THE BASIC DOPAMINE ACTIVITY, THE POSITIVE FOR REWARD, THE NEGATIVE REWARD FOR ADVERSE BEHAVIOR, POSSIBLY RELATED TO LEARNING. SOMETHING THAT HAS WORKED WITH VERY MUCH RECENTLY AND THEN THE OTHERS. SO, SO WHAT WE HAVEN'T LOOKED AT IS THE PROJECTION PATTERN FROM THE SUBSCIENCE AND THE COMPACTOR THAT IS THE DOPAMIN NUCLEUS, OF COURSE YOU DO HAVE IN LAMP RAY AND RODENTS THE PREDICTIONS TO STRIATUM AND THE OTHERS OF THE [INDISCERNIBLE] OF THE BASAL GANGLIA BUT IT TENDS TO BE FORGOTTEN THAT YOU--YOU ALSO HAVE PROJECTIONS TO DIFFERENT BRAIN STEM CELLS, BECAUSE THEY'RE FAIRLY LARGE PROJECTION, TO [INDISCERNIBLE], THE LOCOMOTOR COMMAND REGIONS AND SO FORTH TO WHERE WHEN THESE CELLS ARE TURNED ON RELATING TO STRIATUM, IT'S POSSIBLE THAT YOU ALSO HAVE ACTIVATION HERE. WHETHER YOU'VE GOT TO THE INPUT, HAVE YOU DIRECT INPUT FROM TECTUM, YOU HAVE INPUT FROM THE SENSORY INPUT, FROM THE LATERAL P A LLIUM, AND FOCUSED HERE AND THE NUCLEUS, SO IT'S OF COURSE CRITICAL TO UNDERSTAND WHAT REGULATES THE ACTIVITY IN THIS. RESULTS HERE COLLEAGUES AND OTHER VS SHOWN THE CONTROL OF THE LATERAL HABENULAE FOR THE DOPAMINE NEURONS AND THERE ARE TWO WAYS, THERE IS DIRECT EXCITATORY PATH AND THERE'S AN INDIRECT PATH THROUGH INHIBITION SO CAN YOU ELICIT BOTH EFFECT. SO WE ALSO, SO THE DIPPA MINE NEURONS THEN RECEIVE EXCITATION FROM THE LATERAL [INDISCERNIBLE]. AND THE LATERAL HABENULACE, IN TURN RECEIVES THE SPECIAL PALLET OF NEURONS THAT IS EXCITATORY AND IT PROVIDES EXCITATION, SO IT'S--ALTHOUGH IT'S GLOBEUS PALLETUS, IT'S TONICALLY ACTIVE, IT'S EXCITATORY CONTRAST TO THE OTHERS. IT HAS INPUT FROM STRIATUM AND THE LAMP RAY AT LEAST FROM PALLIUM CORTEX AND CAN INFLUENCE THE LEVEL OF ACTIVITY HERE AND THEREBY THE LEVEL OF ACTIVITY HERE. THE DOPAMINE FEEDS BACK THE NUCLEUS AND THE STRIATUM AND IT IN TURN FEEDS HERE. SO THIS IS THE PARTS OF A QUIET COMPLEX, IT RELATES TO NEGATIVE REWARD, ADVERSE BEHAVIOR AND SO FORTH AND MAMMOTHS AND PRIMATES. BUT WE DO HAVE THESE COMPONENTS HERE FOR IT'S NO TIME, I WOULD NOT GIVE YOU THE DETAILED INFORMATION HERE, BUT LET ME JUST SAY, TWO THINGS THAT THERE ARE TWO--WE HAVE SAID THAT WE HAVE DIFFERENT COMPARTMENTS WITH THE DIRECT PATHWAY AND INDIRECT PATHWAY, BUT WE ALSO HAVE THE OTHERS FRACTIONATION, HISTORY STUDIES OF MULTIPLE ENDOCRINES AND NATRISTUDIES OF MULTIPLE ENDOCRINES AND SHOWN BY ANN GRADY AND COLLEAGUES AND SO FORTH, YEARS AGO. BUT IN THIS CASE IN THE CASE OF THE LAMP RAY, WE SHOW WITH REASONABLE CERTAINTY THE STRISOMES, PREDICT THE DOPAMINE NEURONS DIRECTLY THAT ARE SHOWN BEFORE, BUT IT ALSO PREDICTS TO THE PART OF THE GLOBE AT PARITUS THAT PREDICTS TO THE GPh. SO IT'S PART OF THIS SEPARATE DOPAMINE THAT THEY'RE CONTROLLING THE CIRCUITRY. WHERE IT'S SEEN THAT THE MA ROUGH ATOM STUDIES OF MULTIPLE ENDOCRINE WHICH IS IS NOT [INDISCERNIBLE] PREDICT TO THE CONVENTIONAL GPI, AND DP DIRECT, INDIRECT PATHWAY. SO, IN THE SIMPLIFIED MANNER, ONE CAN SAY THAT WE HAVE A CONNECTIVITY PATTERN WITH STRIATUANDAT UMPIRES SUBDIVIDED IN THE SECTIONS OF THE CELLS AND THIS HAS BEEN SUBDIVIDED BY DENT HISTOCHEMICAL MARKERS AND SO FORTH BUT IT'S VERY DISTINCT THAT YOU HAVE THESE TWO TYPES OF COMPARTMENTS. AND THE STRIOSTUDIES OF MULTIPLE ENDOCRINES THEN--STRISOMES, CONNECT TO THE GPh AND RECEIVE INUTR FROM THE THALAMUS. AND THIS, I WILL THINK IT RELATES TO THE PALLIUM BASED DECISIONS IF YOU DO AN ACTION, IT'S GOOD TO KNOW, THE GOOD OR THE BAD, WHEREAS THE MATRIX COMPONENT GOES TO THE CONVENTION OF THE SNR TO THE CENTERS, ET CETERA. AND WITH THE DIRECT AND INDIRECT PATHWAY. SO IT SEEMS, AND THAT'S MORE CONTEXT OF THE LAMP RAY RELATED TO THE CONTROL OF NOTION, OF COURSE, YOU HAVE THE INPUT FROM THE CORTEX OF THE THALAMUS, IT'S LIKE YOU HAVE TWO DIFFERENT CIRCUITS. HERE, I WILL THEN TALK BEFORE THEN ABOUT THIS GUY ALSO, WHAT CORRESPONDS TO CORTEX. SO--WELL, IT WAS A BIT BEFORE, SO THE BASAL--JUST A SUMMARY HERE, THE BASAL GANGLIA HAS REMAINED UNCHANGED THROUGHOUT EVOLUTION, SO THIS A POINT WHERE THE LAMP RAY DIVERTED FROM THE MAIN LINE SOMETIME AGO. AND THIS SEEMS HERE TO HAVE BEEN RETAINED. THROUGHOUT THIS TIME. SO THE NEXT QUESTION IS CAN THE LAMP PROPEL YOU, CORTEX OR DOES IT CONTRIBUTE TO MOVEMENT CONTROL. AND WE HAVE SHOWN NOW, STILL UNPUBLISHED WORK THAT WE HAVE PROJECTION NEURONS IN THE LATERAL PALLIUM WITH DENDRITES EXTENDING OUT TO THE LAYER, LOOKING A BIT LIKE [INDISCERNIBLE] AND THEY PROJECT--DIFFERENT NEURONS PROJECT TO DIFFERENT AREAS. SO IF--IF WE LOOK AT THE PROJECTION PATTERN, WE HAVE SOME GROUPS OF NEURONS LEFT PREDICT TO THE OPTIC TECT UMKC, FOR THE ORIENTING MOVERMENTS OR CONTROLS DURING MOVEMENTS, WE HAVE ANOTHER THAT GOES TO THE REGION OF THE COMMAND AREA. WE HAVE OTHERS THAT GO DIRECTLY TO THE RETIC LUMSPINAL NEURONS SO IT FORMS A SPINAL CONNECTION, YES, LIKE THE CORE CONNECTIONS. AND THE--BUT WE HAVE THIS ALSO PREDICTIONS TO SNC, THESE ARE THE VERTEBRATES THAT WE HAVE THE PREDICTIONS TO THALAMUS AND SDN CORSPONTENT TO WHAT IS CALLED THE HYPER DIRECT PATHWAY. SO ESSENTIALLY, WE HAVE A LOT OF THE CONNECTIVITY THAT WE KNOW FROM MAMMALS AND PRIME EIGHTS AND THIS IS--PRIMATES AND THIS IS JUST SHOWING YOU THAT THIS THE DEPLAIN OF THE OUTPUT NEURONS LOCATED AND WE HAVE PROJECTIONS, THIS IS ANTERIOR RED FROM PALLIUM AND THE LIMP FADDIC TEGMETTUM, THIS SHOWS A LOT SO CLOSE OF OPPOSITIONS TO MAKE IT TO THE PALIO RETICULAR SPINE PATHWAY. AND WE EVEN HAVE A FEW FIBERS THAT GET TO THE LEVEL OF THE SPINAL CORD. SO THE NEXT QUESTION THEN IS IF WE STIMULATE THIS AREA, CAN WE ELICIT EYE MOVEMENT IN THIS CASE? THIS IS PALLIUM, THIS IS TECH, AND IF WE STIMULATE HERE AND WITH THE A HEAT PLOT HERE WE CAN ELICIT EYE MOVEMENT FROM THIS FAIRLY CIRCUMSCRIBED AREA, WITH THE LOWEST THRESHOLDS. IF WE THEN COMBINED WITH GAZE-ORIENTING, THE CHANGING OF THED HAD, WE CAN ACTIVATE THAT FROM APPROXIMATELY THE SAME AREA. SO ESSENTIALLY WHAT YOU ILLICIT FROM PALLIUM, I WOULDN'T SAY THAT TO THE FRONT, BUT AT LEAST IT'S EYE MOVEMENTS ELICITED FROM WHAT THE CORTEX SOME HUNDRED MILLIONS YEAR AFTERWARDS AND IF WE LOOK ON THE PROJECTION PATTERN, YOU WOULD SEE HERE THAT WE HAVE--THESE ARE NOT STIMULATION POINTS BUT THEY ARE THE LOCATION OF PREDICTION NEURONS GOING TO TECT OWN CO LICKULOUS, AND WE HAVE RECORDED EYE MOVEMENTS AROUND THE EYES AND THEY ARE REPRODUCIBLE EYE MOVEMENT AND WITH DIFFERENT AMPLITUDE AND DIFFERENT FREE RADICALS--FREQUENCY OF STIMULATION SO I THINK IT'S QUITE OKAY. AND IF ONE LOOKS, AGAIN RETURNING TO THE HISTOLOGY AND THE ROUGH PROJECTIONS FROM THE HETEROGRADE STAINING FROM THE TECT UMKC, YOU CAN SEE YOU HAVE GROUPS OF NEURONS HERE THAT PROJECT DIRECTORY TO TECT OHM THROUGHOUT. THEY ARE LOCATED AND PROJECTIONS OF OTHER DOSES THAT ARE CONCERNED WITH THE RETICULAR SPINALS, OR THE MLR, ARE LOCATING IN SLIGHTLY DIFFERENT REGIONS PARTIALLY OVERLAPPING. SO HAVE YOU SEPARATE PROJECTION, NEURONS, SEPARATE GROUP, THAT PROJECT TO DIFFERENT TARGETS. AND YOU CAN ELICIT SWIMMING HERE AS SEEN BEFORE, AND THE NEURONS PROJECTING TO THE MNR REGIONS SO THERE IS AN DIFFERENT CONTROL FROM THE LAMP RAY REPELLANT AT LEAST WITH THE TYPE OF PROJECTIONS IS SIMILAR, SO THE STIMULATION OF THE PALLIUM AS WE SHOW THE MOVEMENT, LOCOMOTION, DISCIPLINARY NOT SHOW MOVEMENT OF THE MOUSE, ALSO QUITE SPECIFICALLY. AND THERE ARE SEPARATE PREDICTION AND NEURONS GOING TO DETECTED OHM AND THE LYMPHATIC LOCOMOTOR REGION AND THE PREJIBBINGSS. IT'S THE OVERALL CONCLUSION HERE IS THAT IT'S IN GENERAL A SIMILAR DESIGN OF THE PROJECTIONS AND OF COURSE, VERY MUCH REDUCED IN SIZES. SO IF I SUMMARIZE THIS AND THAT'S WHERE I USED THE WORD BLUEPRINT THAT WE HAVE MALLIAATIVE SENSORS AND THEY CAN BE ACTIVATED AND THEN WE HAVE SHOWN THAT THE ORGANIZATION, THE BASAL GANGLIA HAVE BEEN THE COMPLEX IS EXTREMELY SIMLER. I HAVE SHOWED YOU LESS ABOUT THE HABENULAE THAT WAS PUBLISHED BEFORE. AND WHAT I COULD HAVE SPOKEN ABOUT INSTEAD IS OUR RECENT DATA ON TECTUM SUPERIOR CO LICKULOUS, THE INTRINSIC ORGANIZATION THERE AND CAN YOU SEE EYE-ORIENTING MOVEMENTS, ET CETERA WHICH AGAIN IS GOOD. RESPIRATORY CPG, WHICH IS IN PROPERTY IS SIMILAR TO THE PRE[INDISCERNIBLE] COMPLEX BUT MOVED A FEW SEGMENTS UP. BUT THAT HAS BEEN DETAILED RECENTLY, ALSO. WE HAVE ALSO THE VESTIBULAR CONTROL OF BODY ORIENTATION THAT AS BEEN ANALYZED IN DETAIL, IN LATIN AND ALSO SIMILAR WITH REGARD TO THE PART. AND THE BRAIN STEM SPINAL CORD IS ALSO ORGANIZED IN A SIMILAR WAY, SO I THINK, TAKING THIS TOGETHER, IT'S REALLY YES, THAT VERY MUCH OF THE BASIC OF THE MOTOR SYSTEM, FROM [INDISCERNIBLE] TO THE SPINAL CORD HAS BEEN--WAS DEVELOPED VERY EARLY ON THE VERTEBRATE, EVOLUTION AND AND IT HAS BEEN OF COURSE DEVELOPED FURTHER IN DIFFERENT ASPECTS AND REFINED BUT ESSENTIALLY THE BASIC PART IS THERE. SO I SOMETIMES NOW USE THE EXPRESSION THAT THE LAMP RAY MOTOR SYSTEM IS FROM THE SPINAL CORD BLUEPRINT OF THE MAMMALAN SYSTEM, I LITTLE BIT LIKE A FORD MODEL T, IT CAN GO FORWARDS, BACKWARDS, YOU CAN STEER IT, IS A GEAR BOX, ET CETERA BUT A FEW THINGS HAVE HAPPENED FROM THIS, I SOMETIMES DOUBT IF WE SULD CALL OUR SPECIES, LIKEN OUR SPECIES TO A FERARY BUT SOME ANIMALS DO BETTER THAN OTHERS. SO THIS JUST REITERATES THAT YOU HAVE THE DILUTION, BUT THE LAMP RAY AT THIS POINT, MAMMALS ARE RELATIVE NEW COMERS AND THESE GUYS ARE--THIS IS--THIS BLOWS OUT OF PROPORTION, ACTUALLY. SO WITH THAT, I WOULD LIKE TO FINISH AND LET ME JUST MENTION MY COLLEAGUES THE MOST RECENT WORK WITH THE BASAL GANGLIA, IN PARTICULAR, THE ROBERSTON MARKERS, STEPHEN SON JONES, VERY TALENTED STUDENT, AND ERICSSON HAS TAKEN PART AND IN THE MORE RECENT WORK ON BOTH THE DOPAMINE CONTROL AND THE PALLIA CONTROL ALSO ON THE VENTRICULAR [INDISCERNIBLE] THE FIRST NAME IS SURYANARAYANA IT'S VERY HARD TO PRONOUNCE, HE IS VERY TALENTED AND I DID NOT SPEAK SO MUCH ABOUT THESE THINGS AND JUST TO PAY MY TRIBUTE TO THIS GUY, THE LAMP RAY. UNFORTUNATELY, THE FINS BUT NOT THE SWEDES MADE THE [INDISCERNIBLE]. OKAY. THANK YOU. [LAUGHTER] [ APPLAUSE ] >> YOU CAN EITHER SPEAK UP OR USE THE MICROPHONE. >> IS THIS ON? >> YES. >> ALL RIGHT. HI, I HAVE A QUESTION ABOUT THE DOPAMINE NEURONS AND WHETHER THEY REALLY ARE CONSERVED ALL THE WAY BACK TO LAMP RAY AND THE REASON IS IN FISH, TELEIOS FISH OR ZEBRAFISH THERE ARE MOW MIDBRAIN DOPAMINE NEURONS AND FOR A WHILE PEOPLE THOUGHT IN THE TUBERC LUMWERE THE HOMOLOGUES OF THE KIND OF FAMILIAR RODENT AND PRIMATES, BTA AND SUBSTANTIAL COMPACTA, BUT A RECENT PAPER FROM BOTH [INDISCERNIBLE] GROUP HAVE SHOWN THAT THE GENE EXPRESSIONS AND THE MORPHOLOGY OF THOSE DOPAMINEERGONS ARE QUITE DIFFERENT. THEY PREDICT DOWN TO THE HIND BRAIN AND SPINAL CORD AS FAR AS I REMEMBER. AND SO, IT'S NOW IN QUESTION WHETHER YOU CAN REALLY TALK ABOUT A HOMOLOGOUS DOPAMINE SYSTEM AT LEAST IN THE FISH, SO--ARE YOU SURE THAT THE DOPAMINE SYSTEM-- >> I MEAN I CAN ANSWER SO FAR AS I KNOW THE THELLUOUS AND THE ZEBRAFISH, EVIDENCE THAT THEY SHOULD BE SOMEWHAT SEPARATE BUT THERE'S A LOT OF STUDIES BY VENYIE AND OTHERS INDICATING THAT WHAT'S THE MIDBRAIN DOPAMINE NEURONS, THEY ARE INITIALLY IN RODENTS AS WELL AS OTHERS FORMED AS A FELLOW, AND INSEVERE MITRAL ALIC PART AND IN SOME--ENCEPHALIC PART, CAN THAT IN SOME SPECIES THE ENCEPHALIC PART BUT THE ZEBRAFISH IS WE RECENTLY SUBMIT THAD PAPER AND WE GOT A QUESTION ABOUT PARTICULARS BUT ALL IN ALL IT'S THERE. AND IF YOU LOOK ON THE PROJECTION PATH, THE PROJECTION PATTERN, IT IS IDENTICAL OF THE DOPAMINE NEURONS THAT GO TO THE BASAL GANGLIA, BUT IN RODENTS, AS WELL AS LAMP RAY, THEY ALSO GO TO THE SUPERIOR CO LICKULOUS VECTOR AND THEY GO THROUGH A NUMBER OF OTHER TARGETS, SO THAT INTENDS TO BE FORGOTTEN BECAUSE YOU HAVE SO MUCH OF THE FOCUS BEING ON THE STRIATUM AND THE PREFRONTAL LOBE. SO I--AM REASONABLY CONVIND. >> OKAY. >> [INDISCERNIBLE]. OR IS THERE A MIXTURE OF OTHER-- >> I MEAN WE HAVE LOOKED IN QUITE SOME DETAIL ON THE INFORMATION, THE PROJECTIONS FROM PALLIUM TO STRIATUM SO WE HAVE A LOT OF PHYSIOLOGY THERE AND I MEAN THESE ARE GLUTAMINERGIC PREJIBBINGSS WITH AN MDA AND AMPA, I MAY HAVE ... I SHOULD HAVE THAT SLIDE. YOU SEE HOW MUCH I AM SORTED OUT. HERE. THIS IS PARTIALLY ANSWERING YOUR QUESTION. SO IT'S A PREDICTION FROM THE LATTER PALLIUM TO THE LATTER STRIATUM AND IT'S FACILITATING SIGN UPS, AND BLOCK WAY AND BQX AND AP FIVE SO YOU HAVE AN NMDA AND A COMPONENT IN THAT, AND WHAT I REFERRED TO EARLIER WAS THE INPUT FROM THE THALAMUS, THE STRIATUM INPUT, IT'S DEPRESSING WITH THE LAST FIRST PART, AND THE OTHER PART, AND AGAIN WITH GLUTAMINERGIC. >> [INDISCERNIBLE]. >> NO, WE ARE STILL WORKING ON THAT, BUT I MEAN WE HAVE THALAMIC INPUT, THE VISITINGIEL THALAMIC INPUT THAT'S GOING TO THIS REGION ACTUALLY AND WE HAVE--OLFACTORY INPUT COMING TO PATHWAYS FROM MICRO CELLS AND ALSO FROM TUOF THED--TUFTED CELLS AND THEY ARE SEPARATE AND THEY PROJECT INTO THE PALLIUM ALSO. THE TUFTED CELL IS VIA RELAY. THIS IS STILL WORK IN PROGRESS, BUT WE HAVE BEEN DOING THAT. SO IT IS, THE THALAMUS IS ORGANIZED IN THE PART THAT DOES QUITE A LOT OF THE INPUT, A LOT OF PROJECTION AND WE KNOW LESS ABOUT THE OTHER PART EXCEPT THOSE THAT PREDICT TO STRIATUM THAT ARE LOCATED IN THE SEPARATE PART FROM THOSE. >> THE DIFFERENT SETS OF PALIO PROJECTION NEURONS [INDISCERNIBLE]--NUCLEAR LIKE AGGREGATE OR HOW ARE THEY [INDISCERNIBLE]--REGIONAL SPECIFICITY--[INDISCERNIBLE] >> I MEAN WHAT I THINK I SHOWED IN ONE OF THE SLIDES IS IS THAT WE HAVE PALLIUM AS RATHER HOMOGEANIOUS PART. I PLEON WE DON'T HAVE IT IN BIRDS WITH SEPARATE NUCLEI AS IT SEEMS. AND WHAT WE CAN SEE, WE HAVE LOTS OF THINGS TO DO ON PALLIUM SO THIS IS JUST THE BEGINNING BUT TO HAVE MORE OF THE PHYSIOLOGY THERE, BUT WE DO HAVE THE NEURONS PROJECTING TO TECT UMKC ARE LOCATED IN A DIFFERENT AREA FROM THOSE STOCK AIDS AND THE CORTICAL, RETICULAR PATHWAYS. SO IT SEEMS TO BE A SEGGREGATION BAH IT DOESN'T SEEM TO BE ANY DISTINCT NUCLEI. >> [INDISCERNIBLE]--YOUR SIMULATION OF THE EYE MOVEMENT--[INDISCERNIBLE]. >> YEAH, THEY ARE NOT QUITE OVERLAPPING BUT IT'S--IT LOOKS LIKE THAT THEY ARE PARTIALLY OVERLAPPING AND THAT THAT CASE, YOU KNOW, IT'S RATHER SMALL STRUCTURE AND YOU USUALLY HAVE--IF YOU ARE IN ONE LOCATION, WITH THE LOW STIMULATION STRENGTH TO GET FOR INSTANCE EYE MOVEMENT WITH A STRONGER STIMULATION, YOU WILL GET SWIMMING OR VICE VERSA. BUT I MEAN IF IT'S TRUE WHAT YOU SAW. >> [INDISCERNIBLE]. >> YOU KNOW THERE WAS A RECENT STUDY PUBLISHED IN SCIENCE BY NICK STRAUSFELT AND FRAN KERTZ, ABOUT A YEAR AGO WHERE THEY SHOWED THAT THE TRANSCRIPTION FACTORS EXPRESS INDEED THE FOREBRAIN OF INSECTS IS VERY SIMILAR TO THOSE THAT ARE EXPRESSED IN INVERTEBRATES. AND THEY ALSO CONCLUDE INDEED IN ARTICLE THAT YOU HAVE A CIRCUITRY, A KIN AT LEAST TO THE DIRECT PATHWAY. YOU HAVE THE DOPAMINE INNERVATION. THERE HAS BEEN AS YOU KNOW PAPERS ON PARKINSONS IN THE FRUIT FLY WHICH HAS SEEMED VERY REMOTE TO ME BUT IT TURNS OUT THAT IT'S ACTUALLY PROBABLY FEEDS BACK TO AN ANABIT WORM OR SOMETHING LIKE THAT AND ANABIT WORM VS TO DECIDE WHERE TO GO AND HOW TO GO AND ET CETERA. SO IT SEEMS THAT THE COMMON ANCESTOR IS-- >> [INDISCERNIBLE]. >> NO BUT FURTHER BACK, THAT'S CONCLUSION, IT'S QUITE EARLY ON. BUT THAT YOU HAVE THIS IS DIVERTED, IT'S ALSO QUITE NICE FROM THE POINT OF VIEW THAT I'VE OFTEN BEEN RATHER SKEPTICAL WHETHER YOU LIKE TO HAVE THEM. THIS IS MODELS, ET CETERA FROM THE FRUIT FLY OR SO, BUT NOW DAYS IT SEEMS TO BE A COMMON [INDISCERNIBLE] IT MAKES MORE SENSE. SO THIS IS--BUT IT'S--WHAT HAPPENED BETWEEN THE ANABIT WORM OR IT'S PREDECESSOR AND THE LAMP RAYS OF COURSE NOW OF COURSE YOU HAVE THE INVERTEBRATE NEURONS LOOKING FOR A DIFFERENT CENTRAL BUT NEVERTHELESS. >> [INDISCERNIBLE]. >> YEAH I MEAN IT'S KNOWN THAT YOU CANNOT THIS EXPERIMENT, SO ONE IS INFERRING THAT THAT YOU ARE HAVING THESE DISCREET SENSES BUT IT'S KNOWN THAT THE DIFFERENT EMOTIONS ARE--IT'S IBT--INTEGRATATE PROPERTY OF OUR SPECIES THAT WE DO SEE IT THAT WAY. AND IF YOU WORK ON PRIMATES OR MAMMALS, YOU CAN--I MEAN IF YOU TAKE THE GRAVE FOR INSTANCE AND YOU STEMMULATE THE PERIDUCTAL GRAY IN A CAT YOU CAN ELICIT WHAT'S--FRIENDLY METRICS OS AND ALSO ALSO MORE AGGRESSIVE HISSING RESPONSES AND YOU CAN ELICIT GREASES OF BEHAVIOR, FROM THE HYPEEE THALAMUS, YOU CAN GET AGGRESSIVE AX TACK BEHAVIOR OR FLEEING, ET CETERA. BUT OF COURSE THE EMOTIONS--EXPRESSION OF EMOTIONS THAT WE HAVE IS MORE AKIN TO DOSE IN PRIMATES AND HAS BEEN FED BACK TO THAT LEVEL. BUT I THINK IT'S FAIRLY SIMPLE TO REGARD THEM AS MICRO CIRCUITS THAT WHEN ACTSIVATED GIVE RISE TO A COMBINED ACTIVATION OF FACIAL MUSCLES PERHAPS. >> ONE FINAL QUESTION? >> ARE THE EYE MOVEMENTS ALL--ARE THERE EYE MOVEMENTS THAT MAINTAIN STABILITY VESTIBULAR [INDISCERNIBLE] ARE THERE ALSO SEPARATE EYE MOVEMENTS THAT YOU WOULD ENGULF [INDISCERNIBLE]. THAT IS A TYPE? >> THERE ARE--THE VESTIBULAR MOVEMENTS CAN BE ELICITED AND HAVE BEEN SHOWN. THE SIR CADIC CONTROL HAS NOT BEEN STUDIED SO FAR. >> DOES IT HAVE AN AREA [INDISCERNIBLE]? >> I MEAN IT DOES HAVE AN AREA IN WHICH I WOULD RATHER MUCH MORE RECEPTORS THAN IN OTHER, BUT IF IT IS FOLIATING [INDISCERNIBLE] I DON'T KNOW. >> THANK YOU VERY MUCH. >> [ APPLAUSE ]