>> I'M DELIGHTED TO INTRODUCE CLAIRE. I HAVE BEEN DREADING THIS MOMENT FOR SOME TIME. CLAIRE IS FRENCH AND ITEMS ON CV HAVE TO BE PRONOUNCED WITH A FRENCH ACCENT I CAN'T DO. THAT THERE IS EMBARRASSING MOMENTS IN THE NEXT MINUTE OR SO. PLEASE FORGIVE ME. CLAIRE HAS AN UNDERGRAD IN NEUROSCIENCE AND PHYSICS FROM ECOLE SUPERIOR AND SHE CONTINUED AND RECEIVED HER PHD IN PHYSICS FROM THE UNIVERSITY OF STRASBURG THAT I CAN PRONOUNCE AFTER PHD SHE SPENT A YEAR TEACHING STUDENTS IN TIBET AND NEPAL AND ENDED UP IN -- WHERE SHE DID ABSOLUTELY SEMINAR RESEARCH IN SDOOEB RA PHISH. THIS IS AISLELY 2000S SHE USE THE OPTO GENETICS IN NEUROBEHAVIOR AND WAS PIONEER IN THE FIELD. SHE USED THIS SYSTEM TO ANSWER A LONG MISTRY? NEUROSCIENCE AND -- NO ONE KNEW WHAT THEY DID. BY USING OPTO GENETIC TRICKS TO MODIFY BEHAVIOR, CLAIRE WAS ABLE TO SHOW NEURONS ARE RESPONSIBLE FOR PROMOTING TONIC DRIVE THAT PROMOTES SWIMMING BEHAVIOR AND AFTER HER POSTDOC WITH EDWARD ISOKOF IN 2007 SHE STARTED HER LAB AT THE BRAIN INSTITUTE AND THAT IS LOCATED IN ILUFT TREOUS -- HOSPITAL, WHICH IS, IN FACT, AN INSTITUTION WITH LONG AND ILUFT TREOUS HISTORY IN FRANCE AND INCLUDES SIGMUND FREUD AND -- THE GUY WHO TER ETS SYNDROME AND JACK [INDISCERNIBLE] INCREDIBLE PLACE AND RESEARCH IS FOCUSED ON MOTOR CIRCUITS AND FIND CLAIRE'S RESEARCH TO BE FASCINATING SHE FINDS COOL SIDELINES BREAKS THEM OPEN TO REVEAL NEW AND EXCITING STORIES. WE WILL HEAR FROM OF THAT TODAY. I MET CLAIRE TWO DECADES AGO AT A ZEBRAFISH MEETING AND IMPRESSED BY HER CREATIVITY AND NEW APPROACHES TO TEST SDOOEB BRA FISH BEHAVIOR AND SHE KELT THAT UP AND DID MATHEMATICAL ALGORITHMS TO APPLY TO ANALYSIS BEHAVIOR AND IS IN FIELD OF ANALYZING ZEBRAFISH CIRCUITS BY APPLYING RIGOROUS AND CREATIVE THINKING. CLAIRE, THANKS FOR VISITING US AND LOOKING FORWARD TO THIS. >>THANK YOU SO MUCH FOR YOUR KIND INTRODUCTION. >>AUDIENCE: [APPLAUSE]. >>IT IS REALLY FUN TO BE HERE AND EXCITED TO SHARE WITH YOU GUYS. NOT SURE IF IT IS CLASSICAL TO ASK YOU TO ASK QUESTIONS DURING THE TALK. I REALLY LOVE WHEN PEOPLE ASK QUESTIONS WHEN THEY DON'T UNDERSTAND AND PLEASE DON'T HESITATE TO USE A MICROPHONE AND ASK QUESTIONS. I'M REALLY EXCITED TO BE HERE AND SPENT A LONG TIME IN THE US AND BECAME AMERICAN AND MY FAMILY IS AMERICAN TOO. IT IS REALLY FUN TO INTERACT AND DISCUSS SCIENCE TOGETHER IN PERSON. AFTER THIS INTRODUCTION, I HOPE I WILL BE AT THE LEVEL THAT YOU EXPECT ME TO BE. INDEED I HAVE BEEN REALLY INTERESTED IN FIGURING OUT THIS QUESTION THAT RELATES TO IPTOCEPTION AND IN BODIES CENSORS DETECTING FLFGS OUTSIDE AND INFORMATION RELATED TO PHYSIOLOGICAL STATE THAT YOU WILL SEE THAT PATHWAY THAT WE DESCRIBED IS REALLY APPARENTLY QUITE CRITICAL FOR THAT. THIS WORK IS THE RESULT OF MANY, MANY, MANY PEOPLE WHO ACTUALLY HAVE BEEN WORKING IN THE TEAM. I REALLY WANT TO SAY THAT, YOU KNOW, IT IS A DECADE OF WORK FROM, YOU KNOW, OUR LAB IN PARRIS. I'M REALLY THANKFUL FOR ALL OF THEM INCLUDING COLLABORATORS AND IF WE STEP BACK AND THINK ABOUT HOW WE CONTROL MOVEMENTS, WHAT IS -- YOU KNOW, PEOPLE HAVE BEEN DESCRIBING, INCLUDING, YOU KNOW, BEAUTIFUL IMAGES FROM OVER A CENTURY OLD WHERE WE WERE INVENTING CONNO PHOTOGRAPHY TO LOOK AT MOVEMENT AND HOW BODY WAS CHANGING OVER TIME AND OUR BODY IS ABLE EVEN FOR US WHO ARE NOT ABLE TO DO THIS KIND OF TALK. OUR BODY IS REALLY ABLE TO ADOPT MANY DIFFERENT POSTURES. WE HAVE MOVEMENTS OF THE LIMBS AND LEGS AND ARMS AND HAS BEEN RESULT OF FOCUS OF OUR UNDERSTANDING OF [INDISCERNIBLE] AND OUR BODY MOVES THE TRUNK AND SPINE IS CHANGING DRAMATICALLY WHEN DOING JUMPS AND TAKING PICTURE AND DOING YOGA LIKE ME YOUR SPINE IS DRAMATICALLY CHANGED AND WHAT IS INTERESTING IS WE HAVE DESCRIBED AND UNDERSTANDING [INDISCERNIBLE] IS FOCUSING ON SPINAL REFLEXES COMING FROM THE SKIN AND MUSCLE TENDON AND MUSCLE SPINDLE AND THIS MUSCLE IS CARRIED TO THE SPINAL CORD AND GENES ARE PROTECTING DIRECTLY AND INDIRECTLY TO MODIFY THE MOTOR CONNECTIVITY OF THE -- THERE COULD BE AN ADDITIONAL SYSTEM PERFORMING ROLE IN PROEP RIOCEPTION AND BEING DRIVEN BY INFORMATION ON THE LIMBS AND INFORMATION ON THE SPINE INDEED, DURING MY POST DOC THANK YOU TO THE GREAT WORK OF ETHAN SCOTT A POST DOC IN [INDISCERNIBLE]'S LAB I HAVE BEEN ABLE TO HELP HIM ON GENETIC SCREEN COMING FROM DROS FILA-AND THERE IS LITTLE CSF CONTACTING NEURON. THEIR EXTENSION IS BASKING IN CEREBRAL SPINAL FLUL AND ONE MICROCILITHAT ALLOW THEM TO POSSIBLY TASTE THE CSF AND THEY HAVE IN ADDITION AN AXON OBSERVED IN EARLY DAYS WHERE [INDISCERNIBLE] DESCRIBED THEM A CENTURY AGO. YOU CAN SEE THEY ARE DRAWINGS THAT ARE RECAPTIVATING HERE THE AXON COMING OUT FROM THE BASAL SIDE RUNNING IN SPINAL CORD AND HINDBRAIN FOR MOST RECENT ONE AND CONTACTING YNS NEURONS IN STRUCTURE IN RED HERE THE REISSNER FIBER THEY PUBLISHED A BOOK IN JERMAN CONTACTING CNSF NEURONS THEY WERE ONLY TWO SCIENTISTS WORKING ON THIS TOPIC THEY HAD A MASSIVE FIGHT. THEY WERE -- IT IS REALLY FUNNY. THEY WERE CONVINCED THIS SYSTEM WAS A SENSORY SYSTEM AND RIGHT HERE THAT IT HAS TO BE A SENSORY SYSTEM IN THE VERTEBRATE SPINAL CORD. THAT THEY AGREED ON AND WHERE THEY REALLY DISAGREE IS ROLE OF REISSNER FIBER THAT IS A POINT AFTER FIXATION THAT IS CLOSE TO THE WALL OF THE CENTRAL CANAL AND STRUCTURE HAD BEEN DESCRIBED BY ANNE REISSNER IN 1860 A REALLY LONG TIME AGO AND DESCRIBED IT LIKE THIS PAPER OVER 50 YEARS AING AND PEOPLE IN THE AUDIENCE FEEL WOW YOU COULD JUST WRITE A PAPER HAVING A RULER AND DRAWING THIS. SEEING UNDER THE MICROSCOPE THERE WAS A POLYMER INSIDE OF THE CENTRAL CANAL RUNNING IN THE LAMPREY FROM THE CERTIFIA VENTRICLE AND TAKE A RULER DRAWING THIS AND THERE IS A STRUCTURE BECOMING THE FIBER MATTER OF FACT IN THE SPINAL CORD AND AFTER HIM MANY PEOPLE DESCRIBE IT IN RAT AND LAMPREY AND IN FROG AND IS PRESENT IN MANY VERTEBRATE SPECIES AND DIAMETER WILL CHANGE DEPENDING ON THE SIZE OF THE ANIMAL AND LARGER IN COW THAN TROUT AND WHAT IS REMARKABLE IS THAT IT IS FORMED AND MADE OF ONLY ONE PROTEIN CALLED FTO RESPONDIN A GIGANTIC PROTEIN OF ALMOST 5,000 AMINO ACIDS. THEY ARE SHOWING THE BEGINNINGS AND FIRST IS ENCODING FOR AMINO DOMAIN HERE THAT IS CRITICAL FOR AGGREGATION AND PEOPLE HAVE STUDIED IT IN THE 80S AND OTHER DOMAIN IS VERY CONSERVED AS WELL APPEARING TO BE IMPORTANT FOR PROBABLY OTHER FUNCTION OF THE SEO FONDANT AND PEOPLE HAVE NOT COMPLETELY UNRAVELLED AND SOME PEOPLE HAVE STARTED COMPANY TO LOOK AT PEPTIDE FROM THE SCO RESPONDIN AND HO IT IS IMPORTANT FOR AXON MIGHT GRAITION IN THE SPINAL CORD AND REGENERATION AND IS A STRUCTURE THAT IS VERY CONSERVE THE AND GOING BACK TO THE NEURON FIRST PUBLICATION WE HAVE DONE WITH LEFT AND RIGHT SYMMETRY IS THAT WE ARE ACTUALLY LOOKING FOR CELLS INMYCIN ZEBRAFISH AND STRUCTURES SP FOR THESE NEURONS AND DESCRIBED NEURONS IN THREE SPECIES ARE PRESENT IN HIGH DENSITY AND ARE NUMERIC IN ADULT SPINAL CORD AND LOOKED AT [INDISCERNIBLE] TO DO THIS AND FOUND THEM IN MICE AND FIND THEM FROM 18 HOURS AFTER [INDISCERNIBLE] IN ZEBRAFISH AND THREE SPECIES COMMON THAT THEY EXPRESS RECEPTOR TO BE NECESSARY FOR TASTING IF IN THE DE SP OT. IN ADDITION TO THAT THEY ARE GABA NEURON AND FOR SENSORY CELLS POTENTIALLY BEING INHIBITORY NEURON AT SAME TIME. IT IS QUITE UNUSHLE. WHAT COULD THEY TASTE IF EXPRESSING A -- RESPOND TO CHANGES IN PH OF MOLARITY SINCE AND ASK OURSELVES WHAT COULD WE OURSELVES BE DOING AND DO THEY INTERACT WITH FIBER TO, YOU KNOW, PERFORM ANY KIND OF SENSORY FUNCTION IN THIS. SO, ONE THING THAT THEY HAD WRITTEN IN GERMAN IS THIS CELL COULD POTENTIALLY BE, YOU KNOW, FORMING THIRD [INDISCERNIBLE] IN THE SPINAL CORD THAT IS WEIRD TO BE FORMED HERE IN THE SPINAL CORD. WAY WE APPROACH THE QUESTION IS REALLY, YOU KNOW, FIRST IN MY POSTDOC WITH THIS AND [INDISCERNIBLE] IN THE LAB IS FIRST BY DOING OPTICAL MANIPULATION AND WE WERE STARTING WITH OPTO GENETICS AND PEOPLE PUBLISHING ALREADY KNEW THE FUNCTION AND THOUGHT IT WOULD BE SO MUCH FUN TO SEE WHAT HAPPENS WHEN WE ACTIVATE NEURONS AND DO EXPERIMENTS AND WHEN I STARTED I WANTED TO HIGHLIGHT AND DEVELOPING TECHNOLOGIES IS QUITE CRITICAL FOR UNDERSTANDING NEW PHENOMENON AND THEY HAD A BEAUTIFUL IDEA BEFORE I JOINED THE LAB TO MAKE RECEPTORS BECOME PHOTOSENSITIVE BY USING THIS MOLECULE PHOTOSWITCH CALLED MAG MADE OF IZO BENZENES CHANGING THIS FROM LIGHT WHEN USING GREEN AND GOES FROM TRANS AND CIS WHEN USING UV LIGHT AND ATTACH ON ONE END AGONIST OF A RECEPTOR COULD BE ANTAGONIST BUT IS AN AGONIST TO BRING GLUTAMATE INTO GLUTAMATE RECEPTOR THAT IS CALLED [INDISCERNIBLE] AND HAS A POINT MUTATION TO BRING IN THE CISTENE TO ATTACH CO-VAILANTLY ON THE LEFT HERE AND THIS WAS WORKING IN CELL CULTURE WHEN I JOINED THE LAB AND MISSION WAS TO GET IT TO WORK IN THE FISH AND TRIED DIFFERENT METHODS TO GET IT TO SPINAL CORD ACTIVITY CELLS WHERE I FIRST INJECTED AND REALIZED I DIDN'T HAVE INJECT AND COULD [INDISCERNIBLE] THE ANIMAL WHEN MOUTH WAS OPEN AND MAG COULD GO IN VERY INEFFECTIVELY AND DID AN EXPERIMENT THAT SOUNDS LIKE A PREHISTORIC OPTI GENETIC EXPERIMENT WHERE I DID THE LIGHTS TO HAVE A DISCO BALL IN MY EXPERIMENT AND SHINED THE LIGHT ON THE PANEL OF THE SPINAL CORD AND USE UV2 ACTIVATOR RECEPTOR AND DO RECEPTOR WITH GREEN LIGHTS LOOKING AT BEHAVIOR OF THE ANIMAL. WHAT I SAW THAT I NEED TO -- YES. CLICK HERE. IT IS THAT UPON THIS SHORT ELIMINATION WITH UV LIGHT I WOULD GET NEAR THE ANIMALS THAT WERE EXPRESSING THIS AND WERE TREATED WITH THE MAG. THIS NIGHT FORWARD-SCREENING RESPONSE. THAT WAS VERY PUZZLING BECAUSE, YOU KNOW, I WAS ACTIVATING SENSORY CELLS THAT ARE INHIBITORY AND HOW CAN I TRIGGER WHAT LOOKED LIKE SPONTANEOUS FORWARD SCREAMING AND TOOK A STEP BACK WHEN IN THE LAB AND ASKING IN FURONES PROJECT ON CENTRAL PATHON GENERATOR TO TRIGGER THIS RESPONSE HOW DO THEY PROJECT NEURONS AND WHAT ARE THEY SENSING TO BE ACTIVATED? LOOKING MORE CLOSELY AT THEIR ANATOMY WE SUE IN ZEBRAFISH THEY HAD A NICE EXTENSION THAT IS SIMILAR TO WHAT IS PRESENT IN OTHER SPECIES INCLUDING THE MOUSE WHERE YOU HAVE LOTS OF MICROVILLI HERE AND ONE SIL YUM THAT IS 9 + 2 ORGANIZATION AND IS A MODI CRIMINALIUM AND IN VIVO HERE AND CRIMINALIUM IS ENABLED WE HAVE LITTLE CRIMINALIUM MOVING IN THE CENTRAL CANAL AND PLAY IN CULTURE SAME THING KINO CRIMINALIUMHAVE LITTLE CILIUM ME CENTRAL CANAL AND PLAY IN CULTURE SAME THING KINO CILIUM MOVING AND THIS IS REMARKABLY ORDERED AND GOING SO RUSTLES TO THE LEFT GOING TO IP SIL ATORAL SIDE AND SIDE OF CELL BODY IF CELL BODY IS ON LEFT, AXON STAYS ON LEFT AND TRUE FOR ZEBRAFISH LARVA. THESE NEURONS ARE CLOSE TO MOTOR NEURONS THAT ARE HERE LIKE SURROUNDING THE CENTRAL CANAL AND THEY ARE SOEM ATTOSTAT AND POSITIVE AND THIS ONE IS NOT LABELED HERE I DON'T EXPRESS IT BUT OTHER PEPTIDES ARE CLOSE TO THE MIDLINE AND THE BROW PLATE AND THEY ARE IN [INDISCERNIBLE] FOR THE MICE. WE HAVE A GERMAN GRAD STUDENT TACKLING QUESTION OF FIRST READING BOOKS OF [INDISCERNIBLE] TOGETHER THANKS WITH HELP. WE LOOKED AT OKAY. LET'S TEST HYPOTHESIS AND IF THEY ARE MECHANOSENSORY AND IF SO WHAT ARE THEY CENSORING WE PUT LARVA IMBEDDED IN [INDISCERNIBLE] AND BROUGHT AN APPLICATION DEVICE HERE TO PRESSURE APPLIES CSF IN VESICLE TO TRIGGER ESCAPE WHERE ANIMAL WILL DO A LARGE TAIL BEND AND HEAD CONFIGURATION TAIL COMES BACK VERY OFTEN AND WE HAVE A SINGLE TAIL BENT AND CAN USE THIS APPROACH TO TELL WHAT CSF CONTACTINGURONS RESPONDING TO THE LARGE TAIL BEND? WE USE THE TO DO THAT AN APPROACH THAT MANY ARE FAMILIAR IN PARTICULAR IN DROSOPHILA YOU USE TWO CENSOR ONE WILL REPORT ON CAPS YUM ENTERING THE CELL AND COMBINE IT A CENSOR FOR POSITION OF THE CELL AND IN THIS CASE [INDISCERNIBLE] SO WE CAN USE A SINGLE, YOU KNOW, WAVELENGTH IN TWO PHOTON MICROSCOPY ELIMINATING AT SAME TIME EFFECTIVELY GREEN AND RED CENSOR SIMULTANEOUSLY SIGNAL FROM GREEN RED AND LOOK AT RATIO SEEING WHETHER THERE IS A SPECIFIC RESPONSE OF THE CELL AND INCREASE IN THE G COUNT YOU DON'T SEE IN THE RED FLUORESCENT PROTEIN AND DOING THAT WE GOT THIS RESULT WHERE THE LARGE TAIL BENT IN THE WILED TYPE ANIMAL WE HAVE CLEAR RESPONSE THAT YOU CAN SEE HERE THAT IS PRESENT AND ONLY IN THE CELL THAT I ENCODED IN RED THAT ARE DOSI LATERAL CELLS ON SIDE OF THE COMPRESSION AND SIDE WHERE MUSCLES ARE CONTRACTING AND ON [INDISCERNIBLE] SIDE, THE STRETCH SIDE, WE DIDN'T HAVE CAPS YUM RESPONSE AND DIDN'T HAVE A RESPONSE EITHER IN THE VENTRAL CSF NEURONS AND ARE RESPONDING ONLY TO COMPRESSION AND DID EXPERIMENT IN PUBLICATION WE TESTED PASSIVE BENT WOULD GET TO SAME RESULTS WHERE WE BEND ONLY TO ONE SIDE AND NEURONS ONLY RESPOND TO SIDE IN THIS CASE CONCAVE SIDE YOU HAVE NEGATIVE CURVATURE AND WE SAID INITIALLY THIS MUST BE A REFLECTION OF SENSING THE FLOOR OF CEREBBRO SPINAL FLUID. THEY ARE IN RIGHT POSITION FOR THIS AND SORRY NEED TO GO BACKWARDS WE HAVE A CLEAR ABOLISHMENT OF RESPONSE INTO THIS PH1 MUTANT HERE WE DIDN'T SEE THIS AT THE TIME AND SAW THERE WAS NUMEROUS RESPONSE OF CSF NEURONS LACKING [INDISCERNIBLE] WE THOUGHT WELL MAYBE PL21 IS NECESSARY FOR THIS MECHANICAL RESPONSE AND MAYBE DETECT THE FLOW OF CSF. SO, THEY JOINED THE LAB AS A GRAD STUDENT AGAIN AND SHE IS DONE RECORDING WHICH I THINK IS REALLY REMARKABLE AND SHE WAS COMING FROM THIS RECORDING IN VOLTAGE CLAMP IN VIVO. WHAT YOU CAN SEE IS SHE COULD FIND SINGLE CHANNEL OPENING BY GOING WHOLESALE AND THIS RESISTOR YOU HAVE SINGLE CHANNEL OPENING THAT YOU CAN VERY NICELY OBSERVE IN THE ANIMAL AT HALF PKD2L1 AND CHANNEL OPENING IS GONE WHEN PKD2L1 IS REMOVED. YES? >>QUESTION. CAN YOU FOR A SECOND EXPLAIN TO WHEN THE THING BENDS THE FLUID IS COMPRESSED IS IT ONLY ALLOWED TO UNDER COMPRESSION MOVE TOWARDS THE HEAD AND THAT IS WHY THE FLOW IS IN THAT DIRECTION OR WHAT IS - >>FOR PEOPLE ONLINE, YEAH. THE QUESTION IS WELL IS THE FLOW CHANGING DURING THE BENDING THAT COULD EXPLAIN RESPONSE OF THE CELL? IT IS COMING IN MY NEXT SLIDE. I'M GOING TO ANSWER THAT QUESTION. SO, INITIALLY WE THOUGHT, OKAY. WELL, SO, THERE IS SPONTANEOUSLY SHOWING ACTIVITY OF THE CHANNEL AND IN THE KNOCKOUT, WE DON'T HAVE SPONTANEOUS ACTIVITY OF THE CHANNEL. WE SEE ON THE RIGHT HERE WHEN WE INJECT A CURRENT THAT IS SIMILAR TO THE SINGLE CHANNEL OPENING, 15 PICO AMP CELLS ARE SO RESISTIVE TO 2 AND GIGA RESISTIVE AND FOR MOUSE AND [INDISCERNIBLE] THAT HAVE BEEN RECORDED AND YOU CAN TRIGGER SPIKING WITH ONE SINGLE CHANNEL OPENING AND IS REMARKABLE AND IS A SENSITIVE SYSTEM. WE HAVE DONE EXPERIMENTS WHERE WE IN CULTURE NOW LOOK AT THESE CELLS AND RECORD THEM WHILE BRINGING AND APOLOGIZE THAT IT SHOULD BE FOUR MICRONS AND FOUR MILLIMETER AND BRING IT TO PUSH AGAINST THE MEMBRANE AND LOOK AT RESPONSE OF THE CELL AND WE FIND THAT WHEN WE DO THAT WE HAVE A [INDISCERNIBLE] WE CAN GET PRETTY FAST, YOU KNOW, PRESSURE APPLIED AGAINST THE MEMBRANE. WE SEE IT CHANGES THE OPEN PROABILITY OF THE CHANNEL AND INSTEAD OF 0 OR 1 CHANNEL OPENING WE CAN GET UP TO 3 AND MODULATION OF OPEN PROBABILITY OF P1 CHANNEL THAT IS UNDER THIS MECHANICAL PRESSURE ON THE MEMBRANE AND IN THE KNOCKOUT FOR PKD2L1 WE SEE WE HAVE ABSOLUTELY NO SPONTANEOUS ACTIVITY AND ALSO HAVE NO RESPONSE TO THE PRESSURE APPLIED AGAINST A MEMBRANE. SO, WE INITIALLY SAID IT HAD TO BE FLOW. WE HAVE DONE RECORDING OF THE FLOW AND MODEL OF THE FLOW THAT I WON'T GO INTO DETAIL BECAUSE IT IS PUBLISHED TWO YEARS AGO. WHAT WE SAW IS THAT IF YOU LOOK AT CSF FLOW IN THE CENTRAL CANAL WHILE THE ANIMAL IS CONTRACTING FROM HEAD TO TAIL, YOU HAVE A VERY NICE EFFECT THAT LOOKS LIKE THE PERISTATIC PUMP EFFECT AND BEADS LABELED HERE ENABLING US TO MONITOR THE FLOW ARE SHOWING A VERY NICE, YOU KNOW, INCREASE OF VELOCITY IN THE DIRECTION OF THE MUSCLE CONTRACTION. IT GOES FROM RUSSELL TO CUDDLE IN THIS CASE TOGETHER WITH MUSCLE CONTRACTION AND COULD BE CONSIDERABLY RESPONDING TO FLOW. WHEN WE LOOK AT THEM NOW WHEN THE ANIMAL IS ALLOWING -- ALLOWING TO SPONTANEOUSLY CONTRACT, WE SEE EMOTION ARTIFACT ASSOCIATE WITH VERY STRONG ACTIVATION OF THE NEURONS THINKING MAYBE IT IS A SIMPLE PROBLEM THAT JUST RESPONDS TO FLOW. WE SAW IT A LITTLE BIT MORE. WE SAID, WELL, COULD IT REALLY BE THAT THEY RESPOND TO FLOW? TALKING WITH PEOPLE INCLUDING [INDISCERNIBLE] WHO IS DOING FLUID MECHANICS WE REALIZE THAT THE FLOW PROFILE LOOKS LIKE THIS IF YOU TRY TO LOOK AT THE VELOCITY OF PARTICLES IN THE FLOW. WHEN CENTRAL CANAL IS, YOU KNOW, ON BOTH SIDES HERE WITH GRAY ON HERE ON THE WALL OF EACH SIDE AND VELOCITY IS IN CENTRAL CANAL AND IN THE CENTER AND FLOW IS PERTURBED DURING MASSIVE FLUSH YOU SEE WITH MUSCLE CONTRACTION, YOU DON'T EXPECT IT TO BE THAT ASYMMETRICAL AND SHOULD BE A LITTLE BIT BUT VERY, VERY MINOR AND BECOMES REALLY COMPLICATED TO THINK HOW COULD IT REALLY TAKE FLOW? IN OUR PAPER WE GENERALLY PROPOSE DISCUSSION AND PROBABLY DETECT FLOW STARTING TO THINK MORE ABOUT REALIZING THEY CAN'T ONLY DETECT FLOW. WHAT IS PROVIDING ASYMMETRY SO THAT ONLY CELLS ON ONE SIDE RESPOND AND DO EITHER LEFT OR RIGHT OR VENTRAL. THERE IS NO -- THERE IS NO SYMMETRY THERE. SO, THAT IS -- SO, WHETHER GENETICS REALLY BECAME CRITICAL, SO, HERE YOU SEE HIM HERE. THEY CAME FROM DROS FILA-AND -- DROSOPHILA AND CHANGING ORGANISM IN CARRIER YOU HAVE TO HAVE FRESH IDS AND DOING EXPERIMENTS YOU DIDN'T THINK OF AND FOR HIM WHEN CRISPR CAME OUT WANTING TO START ON THE TEAM I GAVE HIM THE PROJECT OF TARGETING FIRST AXON OF RESPONDING AND LOOKING AT THE EFFECT OF LACKING THE REISSNER FIBER AND WHAT WAS REALLY GREAT. HE WAS VERY CAREFUL AND GENERATED LEAD STOP CODON EARLY ON IN AXON AND STARTED TO KEEP WE DECIDED IT WOULD BE [INDISCERNIBLE] AND WE CALL ICM15 THEY ARE IN THE PROTEIN 5 AMINO ACIDS ADDED TO AMINO DOMAIN CRITICAL FOR AGGREGATION OF SCO RESPONDING TO A POLYMER AND THOUGHT IT WOULD BE A GREAT CONTROL TO HAVE THIS AND COMPARE IT TO THE NULL. SURPRISE, SURPRISE. WE WERE VERY SURPRISED TO SEE IN TWO ALLELES WE WERE MISSING REISSNER FIBER AND USED IT TO DO THE EXPERIMENT AND YOU SEE COMPARED TO WILD TYPE ON THE TOP HERE IN [INDISCERNIBLE] AND ICM15 ALLELE WERE LACKING THE REISSNER FIBER AND ICM15 WE SEE FLOW PLATE IS STILL SHOWING SIGNALS AND IS RESPONDING AND IT DOESN'T FORM A FIBER. WE HAVE A GREAT SYSTEM TO LOOK AT WHAT IS ROLE OF THE FIBER IN SENSORY SYSTEM AND WHAT WAS TACKLED WAS A QUESTION USING TRANSGENIC LINE AND NEURONS USING PK1 PROMOTER AND FOUND IN ANIMALS LACKING REISSNER FIBER WITH ZYGOTE SHE HAD NO MORE RESPONSE TO BENDING COMPARED TO SIBLINGS SHOWING NORMAL RESPONSES AND DECIDED TO THINK, OKAY. SO, THE NEURONS WE HAVE EXTENSION THAT INTERACT MUST NEED FIBER IN ORDER TO DETECT THE LEFT, RIGHT AND VENTRAL BENDING AND HOW DO THEY DO THAT? WE DECIDED TO LOOK INTO THIS MORE DYNAMICALLY. RYAN GRAY UNIVERSITY OF TEXAS AT AUSTIN MADE A LINE WHERE PUT GFP IN CORRESPONDING LOCUST TO SEE FIBER IN VIVO THIS IS AN ANIMAL WHERE FIBER IS GFP AND YOU SEE THE STRUCTURE IN THE CENTER AND CSF CONTACTING NEURONS EXPRESSING G CAMP AND YOU SEE WHEN FIBER IS IN TACT CELLS ARE FLICKERING AND SHOW A LOT OF ACTIVITY. WHEN WE HAVE BLADES OF FIBER USING A LASER TO REMOVE FIBER, FLICKERING IS MUCH LESS REDUCING LOTS OF SPONTANEOUS ACTIVITY TAKING CLOSER LOOK WITH THIS IN THE TEAM AND WHO WAS THERE AFTER UNDERGRAD FOR ONE YEAR. WE HAVE DONE EXPERIMENTS WHERE WE HAVE LOOKED AT WHAT HAPPENS WHEN WE HAVE BLADES OF FIBER AND LOOKING CLOSELY WHEN OBLATION GOES AND YOU SEE FIBER WITH TIP AND BENDS AND IS PULLING BACK ON BOTH SIDES. IF I PLAY THIS MOVIE AGAIN, YOU WILL SEE THAT WHEN IT IS RETRACTING, OOPS. WHEN IT IS RETRACTING SOME OF THE CELLS ARE GOING TO SHOW WHEN ARE TRANCENT WHEN FIBER BRUSHED THE OPTICAL EXTENSION AND IS REALLY INTERESTING TO LOOK AT THE DYNAMIC ACTIVITY OF THE FIBER, WHICH IS COMPLETELY ACELLULAR WITH INTERACTION WITH THE CELLS AND WE LOOKED AT HOW FAST THE FIBER WAS RETRACTING AND REALIZE THAT THE SPEED AT WHICH THEY RETRACT DEPENDING WHERE WE ARE CUTTING IT. IF CUTTING IT IN THE [INDISCERNIBLE] PART OF THE SPINAL CORD IT WAS VERY FAST AND CUTTING IT IN THE [INDISCERNIBLE] PART IT WAS VERY SLOW AND WENT ACTUALLY BACK TO MY MOTHER WHO IS A PHYSICIST OR THEORIST WHO IS 78 YEARS OLD AND WE NEVER PUBLISHED TOGETHER BUT THINK THIS MIGHT BE THE FIRST PUBLICATION POSSIBLY OF MANY WHERE WE HAVE BEEN LOOKING AT THIS TOGETHER. SHE IS ACTUALLY BEEN MODELING DNA MOLECULE AND HOW REPETITION OCCURS IN DNA MOLECULE IN THE 60S AND ASKED HER HOW CAN WE MODEL THE RICENER FIBER THAT IS MECHANICAL AS WEL MECHANICAL AS WELL -- LOOKING AT RETRACTION MEASURING IN EXPERIMENT SHOULD BE LINEAR WITH A SQUARE ROOT OF TIME AND WEREN'T UNDERSTANDING ANYTHING BEFORE WE HAD FRAMEWORK WHERE WE PLOTTED RETRACTION THAT HAS FUNCTION OF SQUARE ROOT OF TIME AND WE SAW ALL DIFFERENT EXAMPLES OF SALINE WERE MATCHING NICELY PREDICTION AND NICE STRAIGHT LINE GOOD CORRELATION BETWEEN RETRACTION AND DISTANCE AND SOME SQUARE ROOT OF TIME AND YOU SEE IT BECOMES FLAT AND DOESN'T MOVE AND WHEN FIBER IS APPARENTLY STUCK AND TIP OF THE FIBER IS JUST STUCK SOMEWHERE AND DOESN'T MOVE. WE SAID A LITTLE BIT MORE AND SAW THAT WHEN SALINE WAS CUTTING FIBER IN [INDISCERNIBLE] END SHE HAD A VERY FAST SPEED OF THE RETRACTION THAT YOU CAN SEE IN PURPLE HERE. WHEN SHE WAS CUTTING FIBER ON CAUDAL END SHE HAD A VERY SLOW SPEED AND BRINGING BACK TO DIFFUSION COEFFICIENT SHE REALIZED THIS OF MECHANICAL DIFFUSION OF THE FIBER IS THE SAME IN FACT EVERYWHERE AND FIBER IS HOMOGENERALEOUS IN TERMS OF STRUCTURE AND DIE AMOR 4 MILLIMETERS SQUARE PER SECOND BUT WHAT IS DIFFERENT IS ATTENTION ON FINAL ON [INDISCERNIBLE] END AND CAUDAL END. WE ASK WHAT DOES IT MEAN? WE THOUGHT IF FIBER IS A TENSION AND LOOKS LIKE STRAIGHT LINE ON IMAGE ON TOP IT MAKES SENSE. WHEN ANIMAL BEND DUE TO CONTRACTION ON LET'S SAY RIGHT SIDE FIBER WOULD GET YOU KNOW EVEN THOUGH IT IS A SMALL MICRO METRIC DISPLACEMENT GETS CLOSER TO EXTENSION OF THE RIGHT CELL. IT IS REALLY LIKE A ROPE UNDER TENSION AND EXPLAINS THAT CELLS ARE ACTIVATED THANKS TO FIBER BY EITHER INCREASE IN CHANGE OF FLOW OR APPLICABLE EXTENSION IS FOR LARGER FLOW GRADIENT OR THEY ARE DIRECTLY TOUCHING THAT COULD ACTIVATE THE FIBER. WITHIN THE WAY THAT THE TENSION IS BUILDING UP MORE RUST RALLY WE WILL SHOW YOU NEXT. IF YOU LOOK AT CILIA LABELED WITH THIS ACTING DRIVER YOU WILL SEE I DON'T KNOW IF YOU CAN NOTICE THAT MANY CILIA THAT ARE IN FLOW ARE INTERACTING WITH FIBER IN WEAK MATTER AND T POSITIVE CILIA IS OFTEN BIBINDIE FIBER SEE THAT. DOING MORE CALCULATION TO BUILD MODEL TO EXPLAIN TENSION ON THIS SIDE BY WHICH I WILL TRY TO SHOW IT AGAIN. OOPS. IF I GO LEFT HERE, WE HAVE INCREASED TENSION THAT GETS YOU TO WEAK INTERACTION WITH MANY OF THE CILIA THAT IS REALLY BRUSHING FIBER AND OFTEN STICKING TO FIBER AS IF THEY HAVE INTERACTIONS. I THINK THERE IS REALLY SOMETHING ON THE SIGNALING SIDE THAT IS FASCINATING TO LOOK INTO. SO, NOW, GOING BACK TO OUR QUESTIONS, WE ARE CURIOUS BEING INTERESTED IN MOTOR CONTROL WHAT COULD THE SYSTEM DO IN TERMS OF MOTOR CONTROL AND DEVELOPED WITH FIRST QUESTION AND WE HAVE OLIVIA AND FAN KWAUN HERE TRACKING AND PUTTING VECTOR ON HEAD OF THE LARVA AND POINTS ON TAIL AND LOOK AT BEHAVIOR AND QUANTITY FICTION OF ALL TAIL BEND. WE HAVE DONE MANY, MANY MANIPULATION OF SENSORY SYSTEMS AND DISCOVER THERE ARE MULTIPLE EFFECTS AND ONE IS RELATED TO POSTURE AND WAY WE LOOK AT POSTURE AND IN PARTICULAR ROLLING WAS TO USE ONLY ONE CAMERA AND TO USE DEEP LEARNING TO FIND OUT WHERE ANIMAL ROWS ARE TWO EYES OVERLAPPING INSTEAD OF BEING SEPARATED AND GOOD ESTIMATION OF FACT THAT ANIMAL IS ROLLING AND IN TACT ANIMAL PERFORMING A RESPONSE IN A FREELY CONDITION AND BEHAVIOR THAT AREA IS REALLY DESCRIBING EXTENSIVELY. WE SEE THAT ANIMAL TYPICALLY DOESN'T ROLL AND ON CONTRARY ON THIS NEURON AND IT. 1 PROMOTER ANIMAL OFTEN ROLLS AFTER CILIA IS BENT. WE WERE REALLY PUZZLED BY THAT HOW A SYSTEM IN SPINAL CORD COULD EFFECT ROLLING OF THE ANIMAL AND TRUE THAT MOST MUSCLES ARE IN THE TAIL AND HEAD IS HEAVY. IF TAIL IS DOING LARGE TAIL BEND LIKE DOING C BEND COULD LEAD TO ROLLING AND THIS SYSTEM SEEMS TO BE INVOLVED. WE HAVE LOOKED A LITTLE CLOSER AT KIN AUTOMATICS AND FIND THAT EACH TAIL BENT DURING ESCAPE THEY WERE INVOLVING OBLATION OF CNSF CONTACTING NEURON IN [INDISCERNIBLE] PART OF THE SPINAL CORD WOULD SHOW NOT ONLY ROLLING DEFECT BUT DEFECT IN C BENT ITSELF SO PRIOR TO ROLLING AND REDUCTION OBLATION IS GREEN ONE AND SIDE WE HAVE REDUCTION OF C BENT LARGE TAIL BENT AND REDUCTION OF SPEED OF ESCAPE RESPONSE. SO, WE LOOKED MORE CLOSELY AT CIRCUITS AND IS SAD TO PUT ALL THIS DATA THAT IS COMING FROM THREE PUBLICATIONS AND WE HAVE LOTS OF PHOTOGENETICS MAPPING INTO ONE SLIDE AND ALL EFFORT HAS ENABLED US TO UNDERSTAND THAT CSF AXEIIAL SENSORY SYSTEM CSF CONTACTING NEURONS THIS CONNECTING FIBER CAN DETECT BENDING AND MODULATE DIFFERENT CIRCUITS AND THE ONE THAT IS REALLY LOCATED CLOSE TO THE MEDIAL [INDISCERNIBLE] ARE PROJECTING SPECIFICALLY ON LARGE MOTOR NEURONS CALLED CAP THAT YOU CAN SEE HERE. SORRY. HERE. THERE IS ALSO PROJECTING ON TO LARGE SENSORY INTERON INVOLVED IN NEGATING OF MECHANICAL [INDISCERNIBLE] AND METASTATIN YOU CAN SEE HERE ARE PROJECTING ON PREMOTOR INTERNEURON INVOLVED IF IN THE SLOW SWIMMING AND THEN ON THIS SIDE CSF CONTACTING NEURON MOST PROJECTING HOOINTD BRAIN AND WHAT IS INTERESTING IS THEY PROJECT AGAIN ON MOTOR NEURONS AND OCCIPITAL MOTOR NEURON AND PROJECT EXTENSIVELY ON VENTRAL AND DORSOON SPINAL NEURONS FROM THE BRAIN STEM GOING TO SPINAL CORD TO TRIGGER THE MOTOR ACTION. SO, IT IS REALLY FASCINATING. SYSTEM IS NOT ONLY ABLE TO MODULATE ACTIVITY OF SPINAL CIRCUIT BUT GAINS INFORMATION FROM SPINAL CORD OR FROM HINDBRAIN TO SPINAL CORD AND WAY TO PROPOSE IT COULD BE ACTING WE WOULD LOVE TO WORK WITH PEOPLE WHO MODEL ACTIVITY THERE. YOU HAVE A WAVE OF EXCITATION TO GET YOU KNOW LOCOMOTION TO GO FROM RUSSELL TO CUDDLE AND EXTENSORY MOTOR NEURON THAT ACTIVATED AND SENSORY SYSTEM IS DETECTING BENDING CONSEQUENCE OF ACTIVATION AND PROJECT INHIBITION GOING EPSY LATERAL TO SILENCE THAT GOT ACTIVATED TO OPTIMIZE THE [INDISCERNIBLE] OF THE WAVE AND IS PRETTY COMPLEX AND TRICKY YOU CAN'T DO NEURONS WHILE ANIMAL IS MOVING BUT IS WAY THAT WE UNDERSTAND IT. WHERE WE GOT REALLY EXCITED THIS YEAR IS THAT TWO PAPERS CAME OUT FROM THE LAB OF [INDISCERNIBLE] IN GERMANY AND LAB FROM [INDISCERNIBLE] IN JAPAN AND SHOW THERE IS SOMETHING THAT IS CONSERVE THE ABOUT SENSORY SYSTEM IN MICE AND DON'T KNOW YET IF THEY ARE MEK CANOE SENSORY AND IF THEY ARE REACTING FIBER LIKE THEY DO IN FISH AND LAB FOUND REMARKABLY SIMILAR PATTERN OF PROJECTS WHERE EP SIL NEURON AND -- AND THEY ALSO PROJECT ON TO MOTOR NEURONS SO THERE IS SOMETHING THAT IS VERY INTERESTING CONSERVATION BETWEEN ZEBRAFISH AND MOUSE AND WHAT WE WOULD LIKE TO KNOW IS WHETHER THEY ARE SENSING AND WHAT THEY ARE SEN SENSING IN MOUSE AND HOS TOPIC OF INVESTIGATION FOR LABS AND WHAT IS INTERESTING IN PUBLICATION IS THEY FOUND IT WOULD -- WHEN YOU DISRUPT SENSORY SYSTEM REMOVING SIL YUM OF THE CELL KILLING CELL WITH TOXIN YOU FIND REMARKABLE DEFECT IN SPEED OF LOCOMOTION AND WORK OF THIS AND IN CASE OF FINDING INTERESTING DEFECT IN SENSORY -- WHERE ANIMAL IS CHALLENGED ON A SMALL ROD AND WORKING WITH LADDER ON LARGE [INDISCERNIBLE] AND THERE IS INTERESTING COMPARI SEASONS TO BE MADE, I THINK. I WROTE A PIECE ON THE INSIGHT ABOUT THIS. SO, NOW, WHAT IS THE SENSORY SYSTEM GOOD FOR? HOW MUCH DOES IT MATTER FOR PHYSIOLOGY? THIS PATH, WE HAVE TAKEN, YOU KNOW, A VERY -- YOU KNOW, WE HAVE BEEN REALLY EXCITED TO FIND UNEXPECTED FINDING. ON ONE SIDE FOR MECHANOSENSATION AND OTHER FOR [INDISCERNIBLE] SENSATION. FIRST IS FOR MECHANOSENSATION AND GREAT POST DOC BECAME PERMANENT RESEARCHER IN MY LAB. WHAT SHE DESCRIBED WHEN SHE WAS GIVEN THIS FROM PIERRE LUKE LACKING IN RICENER FIBER WAS INCREDIBLE PHENOTYPE ZEBRA FISH AT CERTAIN HOURS WOULD SHOW CURLED PHENOTYPE. COULDN'T BE STRAIGHT LIKE IT NORMALLY IS DURING AMBREE OE GENESIS. IN ANIMAL P12 MUTANT WE SAW SOMETHING DIFFERENT THAT [INDISCERNIBLE] WAS COMPLETELY FINE AND LOOKED COMPLETELY FINE AT JUVENILE STAGE. WHAT HAPPENED IS ADULT AND WE HAVE SEEN THIS OVER FIVE GENERATIONS OF ADULTS WE HAD KYPHOSIS WHERE WE GET INCREASED CURVATURE OF THE SPINE. FINALLY IN MUTANT CORRESPONDENT THAT IS ONE IN PARTICULAR THAT HAS BEEN PUBLISHED BY THE GROUP OF RYAN GRAY AND CONFIRMED BY THE GROUP OF [INDISCERNIBLE] AND ALSO OUR LAB. WE HAVE BEAUTIFUL DEFECT WHEN YOU DON'T REMOVE COMPLETELY THE FIBER BUT EFFECT THE METHOD AND STABILITY OF THE FIBER. WHAT HAPPENED IS THAT IN A -- IN AN APPARENTLY A CORRELATED MANNER WHEN FIBER STARTS TO BE DISRUPTED YOU OBSERVE BEAUTIFUL 3D FORMATION OF SPINE THAT ARE HALLMARK OF IDDIO PATHIS SCOLIOSIS AND LOOKING AT QUESTION AND LOOKING AT RECEPTOR INVOLVED AND AT THIS POINT MANY PAPERS CAME OUT IN THE FIELD IN LAST FEW YEARS WHAT SEEMS TO BE HAPPENING CNSF -- VENTRAL BENDING EXPRESSING FIBER IS IN TACT AND PEPTIDE IN FAMILY OF THIS TOO AND PEPTIDE WHEN RELEASED COULD ACT RECEPTOR THAT IS TS3 AND RECEPTOR IS PRESENT IN DOSCULAR MUSCULAR ALLOWING BODY TO BE STRAIGHT IN THE EMBRYO AND JUVENILE SITUATION IS STILL INVOLVING THE [INDISCERNIBLE] RELATED PEPTIDE AND RECEPTOR THAT IS A LITTLE BIT UNCLEAR AT THIS POINT IF THERE IS ONLY, YOU KNOW, A ROLE OF CSF CONTACTING NEURONS VIA PEPTIDE OF OTHER STRUCTURES THAT ARE INVOLVED AND REALLY CURIOUS TO KNOW IF IN HUMANS SOME PATHWAY IS CONSERVED TO GET US TO NOT GROW CURVED SPINE AND IS INTERESTING THAT IN HUMANS PEOPLE HAVE LOOKED AT THIS IN CONTEXT OF [INDISCERNIBLE] IN MICE AS GROUP OF [INDISCERNIBLE] HAS SHOWN THAT DORSOGANGLIA MATTER FOR THIS AND CAN GET SCOLIOSIS IN MICE IF THEY EFFECT SENSORY FUNCTION OF DORSOGANGLIA AND USE TWO FEET TO GET THIS INFORMATION FROM THE GROUND. IT IS REALLY UNCLEAR IF CSF CONTACTING NEURONS WOULD BE IMPORTANT FOR THIS FUNCTION AND WE ARE INTERESTED TO GO IN THAT DIRECTION. NOW, THE LAST POINT THAT I WOULD LIKE TO PRESENT IS A WORD THAT IS PUBLISHED RECENTLY BY [INDISCERNIBLE] WHO IS A FORMER POST DOC IN THE LAB AND GOT IDEA IN 2014 THAT I HEARD A TALK ABOUT MENINGITIS. I THOUGHT HAVING A SYSTEM THAT CAN TASTE ACID IN THE SPINAL CORD COULD BE VERY RELEVANT TO MENINGITIS. IT IS A BIT OF A CRAZY IDEA AND DIDN'T COME UP TO BE COMPLETELY USEFUL AND WHEN THEY PROLIVE RATE THEY CHANGE PH AND PROLIFERATING IN CSF WE HAVE [INDISCERNIBLE] THAT COULD RECRUIT CELLS AND BE INVOLVED IN CHANGING THE STIFFNESS OF THE NECK AND IN GENERAL WE TALK ABOUT STIFFNESS OF THE NECK FOR MENINGITIS AND IS WHOLE BODY BECOMING RIDGID WITH [INDISCERNIBLE] MUSCULOCULTURE BECOMING STIFF AND THOUGHT MAYBE THERE IS A LINK AND SEARCHING LITERATURE TO LOOK FOR A WAY TO GET MENINGITIS TO GET ZEBRAFISH AND CAME OUT WITH A PAPER AND BOOK IN LAB IN AMSTERDAM DESCRIBING IF YOU FUSE THIS WITH GFP YOU COULD GET A BEAUTIFUL VISION OF ENTIRE CSF INNIJECTIN BACTERIA INTO IT AND CALLED HER AND YES LET'S COLLABORATE WITH EACH OTHER AND USE IN LAB THIS BACTERIA IS [INDISCERNIBLE] TO INJECT TWO DAYS IN VENTRICLE AND LOOK AT PROLIFERATION OF THE BACTERIA TO SEE THAT AT BOTTOM IMAGE HERE YOU HAVE A NICE FILL OF THE CSF IN THE CENTRAL CANAL AFTER 24 HOURS. WE ASK OURSELVES WHAT HAPPENS WHEN THE ANIMAL IS INFECTED AND WHAT IS REALLY COOL IS THAT THEY CHANGE CURVATURE IN THE OPPOSITE DIRECTION WHAT I HAVE SHOWN YOU IN THE PHENOTYPE AND LIKE THE RICENER FINAL YOU CURL DOWN AND ACTIVATING CELLS THAT RELEASE YOUR ATTENTION AND PEPTIDES YOU CURL UP AND WHAT IS INTERESTING IS EFFECTED ANIMAL STRIKINGLY SHOWS CURLED UP PHENOTYPE AFTER THE INFECTION AND IS SIGN THAT SENSORY SYSTEM IS INVOLVED IN TRIGGERING THIS RESPONSE. WHAT IS REALLY FASCINATING AND, OF COURSE, AND THANKFULLY NOT SEEING TOO MUCH IN OUR COUNTRIES BUT IF YOU DON'T TREAT PATIENT WITH MENINGITIS AND BACTERIA COLONIZED CAN YOU HAVE [INDISCERNIBLE] WHERE PERSON OR KID WILL SHOW BACK BENDING SAME I HAVE SHOWN YOU FOR YOGA BUT THIS TIME UNWANTED INVOLUNTARY BACK BEND WHERE THEY CAN'T ESCAPE FROM BACK BENDS AND CURIOUS ABOUT THE PHENOTYPE AND ASK OURSELVES CSF RECRUITING FUNCTION AND BACK BEND THAT IS LIKE DOING CAT EXPERIMENT IN OLD DAYS WE ARE 24 HOURS ON MICROSCOPE AND LOOKING AT 12 FISH INJECTED WITH PBS AND 12 FISH INJECTED WITH BACTERIA AND RECORDING CSF CONTACTING NEURONS IN FIELD HERE FOR FIVE MINUTES REPEATING IT 12 TIMES AND WHAT WE DID WHEN WE DID THIS IS COMPARED TO CONTROL WHERE YOU HAVE LITTLE FLICKERING OF CSF CONTACTING NEURONS ANIMAL WHICH BACTERIA STARTS TO PROLIVE RATE HAS TO BE LIVE BACTERIA TO GET EFFECT AND YOU HAVE REDUCTION OF BASAL ACTIVITY OF THE CELLS THERE IS LESS FLICKER IING THAT ARE LARGER THAN WHAT YOU SEE IN THE CONTROL CASE AND WE QUANTIFY THAT AND DESCRIBE THAT INDEED A SUBSET OF THE CELLS IS RECRUITED FORMATICALLY AND IS SAME AFTER YOU GO EVERY TWO HOURS AFTERWARDS AND NOT LIKE IT IS OCCURRING DURING INFECTION AND USE A TOOL THAT IS GIVEN BY HARRY HERE TO OBLAT THE CELLS ONLY AND LOOK AT EFFECT AND WHEN WE HAVE DONE THAT SEEING WE HAVE A CLEAR EFFECT ON THE SURVIVAL AND ANY ANIMAL ON SENSORY SYSTEM IS SHOWING REDUCTION OF SURVIVAL AND SENSORY SYSTEM IS DOING SURVIVAL OF THE HOST BLOCKING SECRETION FROM NEURONS USING THIS WE GET SAME PHENOTYPE OF DECREASING SURVIVAL THAT ASSOCIATES INCREASE IN NUMBER OF BACTERIA THAT CAN COUNT IN NUMBER OF ANIMAL AND GOING FAST CONCLUDE CONCLU CONCLUDING THIS TASTE RECEPTOR AND COMING FROM T2R FAMILY AS WELL AS T1R RECEPTORS COULD BE INVOLVING TASTING BACTERIA AND MUIRO PEPTIDE [INDISCERNIBLE] AND ATTRACTING MICROFAITH AND HAVE BEEN REPORTED HAVING ANTI-MICROBIAL FUNCTION AND TESTING IN VITRO AND WE GET VERY LARGE RESPONSE WITH DMDS AND [INDISCERNIBLE] WHICH ARE MOLECULES THAT ARE NATURALLY SECRETED BY BACTERIA THAT COULD BE EFFECTIVE IN ACTIVATING NEURON AND FIND UPON INFECTION THAT THIS IS DRAMATICALLY CHANGING WITH NEURONS EXPRESSING CYTOKINES AND [INDISCERNIBLE] FACTORS AND ALL IN ALL WE HAVE SHOWN THAT TOGETHER CONVERTING THIS TO PROPOSE THIS SYSTEM WHETHER SENSORY SYSTEM IN ADDITION TO BEING IMPORTANT FOR MECHANOSENSING TOGETHER WITH RICENER FIBER GIVING CREDIT TO [INDISCERNIBLE] ON THIS ONE THEY WERE CHEMOSENSE YRY AND TASTING CONTENT OF THE CSF AND RESPOND TO IT BY RELEASING PEPTIDES AND DIFFERENT SECRETED PROTEIN ACTING NOT ONLY LOCALLY IN THE SPINAL CORD AND MORE BROADLY RECENT YOO R IN THE MUSCLE TO CHANGE POSTURE AND CHANGE EVEN MORPHOGENESIS AND SHAPE OF THE SPINE THROUGHOUT LIFE. SO, THIS IS WHAT WE HAVE DONE. I WILL JUMP TO MY ACKNOWLEDGMENT SLIDES. AND THANK YOU ALL FOR YOUR ATTENTION. THANK YOU IN FACT ALSO THE NIH. WE HAVE BEEN SUPPORTED BY NIH TO DO THIS WORK THAT IS REALLY KEY TO OPERATE IN FRANCE. NOTHING WAS EASY TO GET FUNDING. THANK YOU VERY MUCH. >>AUDIENCE: [APPLAUSE]. >>WHEN ZEBRAFISH AND LARVAL ZEBRAFISH SWIM THEY HAVE KIND OF -- THEY SWIM BY FLEXING THEIR BODY THAT IS OBVIOUSLY VERY DIFFERENT TO MAMMALS THAT DON'T DO YOGA. >>YEAH. >>DO YOU THINK THERE IS ANY SIMILARITY? IS THERE ADAPTATIONS OF THE SYSTEM THAT COULD WORK IN MAMMALS TO PROMOTE LOCOMOTION, FOR EXAMPLE? >>YEAH. IT IS A QUESTION THAT WE ARE REALLY THINKING A LOT ABOUT. SO, [INDISCERNIBLE] LAST YEAR HAD A PUBLICATION AND WE HAVE [INDISCERNIBLE] IN LAB AND THEY DESCRIBE A CENSOR IN SPINAL CORD THAT COMES IN A JUVENILE STAGE THAT TOOK GLYCOGENIC NEURON THAT LOOKED LIKE EDGE CELL DESCRIBED IN 1984 THAT IS A STRETCH CENSOR AND OPPOSITE OF THESE GUYS WERE COMPRESSION CENSORS. CENSOR KNOWN AS [INDISCERNIBLE] TO BE RESPONDING TO STRETCH AND [INDISCERNIBLE] AND IS ALSO IN THE SPINAL CORD. I THINK IT IS HIGHLY POSSIBLE THAT IN HUMANS AS WELL YOU WOULD HAVE A SERIES OF DIFFERENT CENSORS AND FEEL LIKE IN ZEBRAFISH TOO WE DON'T KNOW AND MANY CELLS WE HAVEN'T BEEN DISSECTING VERY MUCH IN SPINAL CORD COULD HAVE MORE FLUIDITY TO IN ADDITION TO SOME OF THE [INDISCERNIBLE] NEURONS LOOK LIKE THEY COULD BE MEK CANOE SENSORY AND HOW MUCH IS A SYSTEM CONSERVED IN [INDISCERNIBLE] AND HOPING TO LOOK AT THIS. AT THIS POINT, MY BET BUT IT IS REALLY A BET. IT IS THAT I THINK THE CSF CONTACTING NEURONS WOULD PROBABLY BE CONSERVED AND I'M NOT SURE. I BELIEVE THAT RICENER FIBER MIGHT NOT BE FROM A FIBER IN ANIMALS. I'M NOT SURE ANYMORE. LOOKING IN ADDITION OF GENOME AND NOT MY EXPERTISE AND PEOPLE IN THE ROOM MIGHT KNOW THIS BETTER IS NOTED AT [INDISCERNIBLE] STARTING FROM GORILLA AND BASICALLY THE GREAT APES AND LOOKS TO ME 10 MILLION YEARS AGO BECOMING BIPEDAL WE MIGHT HAVE USED LOOKING AT IT IF EXPRESSED IT IS A CHUNK OF IT AND NOT SURE WE HAVE A RICENER FIBER AND SOMETHING TO TEST. IN MY LAB [INDISCERNIBLE] WAS TELLING ME I'M LOOKING AT IT IN HUMANS AND KNOW HE RETIRED AND NEVER SAW ANY PUBLICATION COMING OUT. IT IS A BIT OF A MYSTERY TO BE HONEST THAT WOULD BE INTERESTING TO HEAR. I'M CURIOUS TO TALK WITH PEOPLE LOOKING AT SPINAL CORDS IN HUMANS TO BE HONEST. I WANT TO SEE IF WE SEE MARKERS OF THE CELLS. YEAH. IT IS A BIT IF YOU HAVE A TEAM. YEAH. >>THANK YOU. >>HI. YES. >>FIRST OF ALL, BEAUTIFUL WORK. I'M WONDERING THE IDEA WITH ALL NEURONS HAVING A PROJECTION THAT IS CONTACTING THIS [INDISCERNIBLE] AND I WAS WONDERING IF IT IS IMPORTANT FOR BINARY OF THESE CELLS THAT THEY ARE NOW GOING TO BE COORDINATED AND THEY HAVE [INDISCERNIBLE]. >>I THINK YOU ARE RIGHT. >>IT IS IMPORTANT FOR [INDISCERNIBLE] OR COORDINATION. >>YEAH. I THINK IT IS REALLY -- I THINK IT IS VERY TRUE. SO, IN THIS MUSCLE FIBER IS [INDISCERNIBLE] AND PREPARING PUBLICATION ON THIS AND THINK THAT IN FISH, RIGHT, IT IS SO EASY TO IMAGINE IT. IT IS CLEAR IT IS FORMING [INDISCERNIBLE] AND CLEAR THAT THEY BEHAVE LIKE TODDLERS IN A BIT OF [INDISCERNIBLE] AND FIBER IS THERE TO BRING THIS ATTENTION AND UNABLE TO REALLY LIKE GET THEM ALL TOGETHER. THEN WHAT IS REALLY INTERESTING IS THAT IN MOUSE, WORK OF [INDISCERNIBLE] AND CONFIRMED BY [INDISCERNIBLE] IS SHOWING THEY PROJECT ON TO EACH OTHER SOMETHING THAT WE DIDN'T FIND OURSELVES. SO, I'M CURIOUS TO THINK WHETHER IT IS A DIFFERENT EFFECT THAT CONNECTION WOULD COME LATER DURING DEVELOPMENT OR PROJECTION FORMING RECURRENT NETWORK OF INHIBITION COULD ACTUALLY PARTICIPATE TO FUNCTION AS WELL OF SYNCHRONIZING AND OPTIMIZING PROPULSION OF THE WAVE AND DON'T KNOW HOW YOU FEEL ABOUT THIS BUT FEEL WE NEED TO HAVE DYNAMIC MODEL HOW SPINAL CORD OPERATES AND MANY PEOPLE FINDING INTERESTING GOING TO BRAIN STEM NOW THAT IS GREAT AND I'M EXCITED AND FOUND OUT WE STILL HAVEN'T FIGURED OUT A LOT OF THE QUESTION OF HOW SOME NEURONS, YOU KNOW, REALLY ACT IN PARTICULAR IN GENETIC MANNER WHEN YOU HAVE MUSCLE CONTRACTIONS AND THINK THAT MANY INTERESTING WORK IN THE MICE ARE SHOWING ALSO REALLY IMPACT OF MEK CANOE SENSORY IMPACT AND IT IS TIME TO BE [INDISCERNIBLE] ABOUT MODELING IT DYNAMICALLY AND GOING BACK TO YOUR QUESTION TOO. IT IS REALLY A BIT -- IT IS A BIG MYSTERY TO UNDERSTAND WHETHER, YOU KNOW, SPINE REALLY MOVES THAT MUCH AND CONTRIBUTES THAT MUCH AND AT SAME TIME THINKING THAT IF YOU DON'T HAVE SENSORY TO DETECT WHERE TRUNK IS MOVING AND USING ONLY FORMATION FROM THE LIMBS YOU ARE MISSING OUT; RIGHT? I FEEL THERE IS A RESULT OF THIS TELLING US THAT IF YOU MOVE CILIA OF THE CELL OR [INDISCERNIBLE] YOU SEE DEFECT IN FINE LOCOMOTION WHEN [INDISCERNIBLE] IS CHALLENGED OR ON THE LADDER AND IT IS NOT EXPECTED FROM JUST MOUSE MOVING AROUND THEY WOULD USE THIS INFORMATION FROM THE SPINE. I THINK IT WOULD MAKE SENSE TO USE IT. BUT FOR HUMAN, IT IS A BIG MYSTERY AND CURIOUS TO SEE WHETHER YOU HAVE DATAS ON HUMAN THAT WE CAN LEARN FROM. THANK YOU. >>AMAZING TALK. >>THANK YOU. >>MY QUESTION IS A FOLLOWUP ON YOUR FIRST -- SOMETHING THAT IS IN THE RESPONSE TO THE FIRST QUESTION. SO, IN TERMS THAT YOU SHOWED IN THE BEGINNING DIFFERENT ANIMALS LOOK VERY DIFFERENT WEISSNER FIBERS AND HUMANS HAVE LESS AND COWS HAVE THIS GIANT THING IS THERE FRAMEWORK YOU CAN CORRELATE THAT? >>MANY CRAZY THEORIES BUT DON'T KNOW IF THERE IS A SERIOUS ONE. WE HAVE A WEBSITE ON -- FROM SOMEONE I THINK IN OHIO THAT THINKS WEISSNER FIBER IS KEY TO CONSCIOUSNESS AND YOU CAN SEE THIS CRAZY OUT THERE AND IT IS REALLY A STRETCH AND TRUE THAT THERE ARE SPECIES WHERE THEY HAVEN'T FOUND IT AND QUESTION IS WHEN YOU HAVE A MO MONOMER SO BIG AND FOUND A LONG STRUCTURE THAT IS LONG IN THE GOUT, HOW CAN YOU MANAGE TO KEEP IT. YOU KNOW? STRAIGHT AND NOT TO BREAK IT; RIGHT? SO, IT IS REALLY INTERESTING AND OPEN QUESTION AND REALLY WE HAVE THIS OPEN AND I LOOK AT THIS IN THE GENOME AND IN LAB WE HAVE [INDISCERNIBLE] AND YOU KNOW, IT IS REALLY INTERESTING TO FIGURE OUT IF IT WOULD BE [INDISCERNIBLE] AND IF SOMEBODY MEANT TO CONTRIBUTE TO THE [INDISCERNIBLE] AND NOT FORMING THIS NANOFIBER. SO, PHYSICIST WE WORKED WITH TO DO THE MODEL WITH THIS VALUE OF ELASTIC MODEL OF THE FIBER, IT HAD TO BE A LITTLE BIT SEEN AS A [INDISCERNIBLE] AND MEANING THAT [INDISCERNIBLE] AND THERE IS AS MUCH CROSS-POLLIN NOT POLYMERIZED AND CROSS-POLLIN POLYMERIZED AND STRUCTURE OF IT IS LIKE GELL AND IS MYSTERIOUS IF ONLY IS FORMING A ROPE OR ACTION IN ACCESSORY SIGNALING IN CSF IN FACT. YEAH. NOW, I HAVE A QUESTION OF [INDISCERNIBLE], PLEASE. >>[INDISCERNIBLE]. >>GOOD. >>[INDISCERNIBLE]. >>SO, YEAH. WE ARE STILL -- IT IS VERY FRESH AND IN MY MIND I SUBMITTED THE PAPER RECENTLY AND WE ARE STILL PROCESSING IT AT THE TIME AND TAKES TIME AND QUESTION WE ARE STRUGGLING WITH IS HOW YOU GET A STRUCTURE TO BE IN TENSION IN VIVO AND IF A GUITAR STRING DOES IT MEAN YOU HAVE TO PULL ON TWO ENDS? IF YOU PULL ON TWO ENDS IT MEANS YOU WOULD BE REALLY -- YOU HAVE TO ADJUST THE PULLING IN A VERY FINE MANNER TO GET IT TO PULL THE RIGHT WAY BUT NOT PULL TOO MUCH AND IS A LITTLE BIT UNCLEAR HOW YOU WOULD ACTUALLY GET A STRUCTURE TO BE UNDER TENSION IN VIVO TO HAVE STRAIGHTNESS AND THINK IT IS THE BEGINNING OF THIS. WE DON'T HAVE AN ANSWER YET. IT IS VERY HARD TO MANIPULATE BEATING OF THE CILIA ONLY. I THINK WHAT WE KNOW AND HAVE SEEN IS IT CAN POSSIBLY EXPLAIN THAT CILIA THAT I SHOW THE IS CILIA NOT ONLY OF CSF CONTACTING NEURONS BUT THOSE CONTRIBUTING AND GENERATING FLOW HAVING LONG MODAL SIL YUM YOU SEE CLEARLY INTERACTION BETWEEN ORIENTED TO CAUDAL END AND POLARITY AND INTERACT OFTEN WITH THE TIP OF THE CILIUM AND CREATING THIS TENSION AND INTERACTION EVEN WEAK YOU CAN BUILD UP TENSION AND ENABLE WITHOUT HAVING A SMALL SYSTEM WITHOUT PULLING ON BOTH ENDS TO KEEP TENSION THERE. BECAUSE FLOW OF VELOCITY WE HAVE MEASURED ARE NOT SUFFICIENT TO PUT FIBER ON TENSION AND NOT LIKE YOU HAVE A RIVER INSIDE OF THE BODY. IT IS ACTUALLY QUITE, YOU KNOW, SLOW. I THINK IT IS A GOOD WAY TO EXPLAIN THE TENSION AND THINK WE NEED TO, YOU KNOW, BUILD A MODEL TO UNDERSTAND IT. WE HAVEN'T BEEN THERE YET. OKAY. THANKS SO MUCH! >>AUDIENCE: [APPLAUSE]