Project Grant F31NS151812

HINDBRAIN PATHWAYS FOR VESTIBULAR CONTROL OF POSTURE IN LARVAL ZEBRAFISH - PROJECT SUMMARY/ABSTRACT UNDERSTANDING THE NEURAL CIRCUITS BEHIND BALANCE REGULATION IS IMPORTANT BECAUSE THE INABILITY TO BALANCE CAN RESULT IN FALLS, WHICH CAN CAUSE SERIOUS INJURIES. BALANCE ISSUES ARISING FROM CENTRAL VESTIBULAR DYSFUNCTION IN THE BRAINSTEM ARE ESPECIALLY HARD TO TREAT DUE TO OUR LIMITED UNDERSTANDING OF THE BRAINSTEM PATHWAYS THAT TRANSFORM SENSORY SIGNALS INTO STABILIZING MOVEMENTS. PREVIOUS RESEARCH HAS CHARACTERIZED SEVERAL VESTIBULO-SPINAL PATHWAYS THAT ORIGINATE FROM THE VESTIBULAR NUCLEI IN THE HINDBRAIN AND PROJECT DOWN THE SPINAL CORD TO DIRECTLY REGULATE POSTURE. HOWEVER, LOCAL HINDBRAIN PATHWAYS THAT CONTRIBUTE TO POSTURE REGULATION INDIRECTLY VIA MULTIPLE SYNAPSES REMAIN UNDERSTUDIED. IT IS CHALLENGING TO STUDY THE HINDBRAIN INDIRECT NEURAL CIRCUITS THAT ARE INVOLVED IN POSTURAL CONTROL IN MAMMALS BECAUSE THESE CIRCUITS MOSTLY INVOLVE A NON-(VESTIBULAR) NUCLEAR HINDBRAIN STRUCTURE, THE RETICULAR FORMATION, THAT HAS A DISTRIBUTED, HETEROGENEOUS NATURE THAT NECESSITATES A POPULATION-LEVEL APPROACH. IT IS HARD TO SIMULTANEOUSLY RECORD ACROSS DIFFERENT HINDBRAIN REGIONS IN MAMMALS, AND THE RECORDING METHODS ARE INVASIVE, WHICH WOULD DAMAGE THE DENSE FIBERS OF PASSAGE IN THE HINDBRAIN. THIS PROJECT PROPOSES TO FURTHER DEFINE THE HINDBRAIN PATHWAYS THAT ARE INVOLVED IN SENSORIMOTOR POSTURE REGULATION USING LARVAL ZEBRAFISH, WHICH ALLOWS NON-INVASIVE POPULATIONAL IMAGING IN A HINDBRAIN THAT DEMONSTRATES CONSERVED NEURAL ARCHITECTURE. IN AIM 1, I PROPOSE TO DEFINE THE NON-NUCLEAR HINDBRAIN NEURONS THAT PRODUCE THE PITCH RIGHTING REFLEX, A HIGH-THROUGHPUT STABILIZING BEHAVIOR TIED TO LOCOMOTION IN FISH.. IN AIM 2, I WILL FURTHER EXPLORE THE NEURAL CONNECTIVITIES OF THE HINDBRAIN SURROUNDING THE VESTIBULAR NUCLEI USING IN VIVO TRACING AND EM RECONSTRUCTION. I WILL COMBINE IN VIVO TWO-PHOTON CALCIUM IMAGING, GENETICALLY TARGETED PERTURBATION, BEHAVIORAL QUANTIFICATION, AND ELECTRON-MICROSCOPY-BASED CIRCUIT RECONSTRUCTION TO IDENTIFY HOW SPECIFIC HINDBRAIN POPULATIONS CONTRIBUTE TO MAINTAINING BALANCE DURING SWIMMING. THE RESULTS WILL ADVANCE OUR UNDERSTANDING OF SENSORIMOTOR INTEGRATION AND ENRICH OUR MECHANISTIC FRAMEWORK FOR HOW VERTEBRATE BRAINSTEMS COMPUTE STABILIZING MOVEMENTS. DURING THE PROPOSED TRAINING PERIOD, I WILL FURTHER DEVELOP SKILLS IN COMPUTATIONAL MODELING, STATISTICAL METHODS, EM PROOFREADING, AND SCIENTIFIC COMMUNICATION. UW-MADISON, AS WELL AS MY GRADUATE PROGRAM, NEUROSCIENCE TRAINING PROGRAM, HAS A RICH AND COLLABORATIVE RESEARCH ENVIRONMENT THAT WILL SUPPORT MY TRAINING THROUGH COURSEWORK, COLLABORATIONS, AND SEMINARS. ADDITIONALLY, I WILL ALSO TRAVEL TO CONFERENCES TO COMMUNICATE MY SCIENCE TO THE BROADER NEUROSCIENCE COMMUNITY. TOGETHER, THESE EFFORTS WILL HELP ME DEFINE HOW HINDBRAIN PATHWAYS CONTRIBUTE TO BALANCE REGULATION, WHILE ALSO SUPPORTING ME IN DEVELOPING MY CAREER AS A VESTIBULAR NEUROSCIENTIST.