DIFFERENTIAL MODULATION OF SPINAL SENSORY AND MOTOR CIRCUITS THROUGH SPATIALLY CONSTRAINED SEROTONIN RELEASE - PROJECT SUMMARY SEROTONIN IS A NEUROMODULATOR WHOSE ROLES IN NEUROPSYCHIATRIC CONDITIONS LIKE ANXIETY AND DEPRESSION ARE WELL KNOWN. HOWEVER, THE ROLES THAT SEROTONIN PLAYS IN REGULATING BEHAVIOR THROUGH THE MODULATION OF SPINAL SENSORY AND MOTOR CONTROL ARE LESS UNDERSTOOD. I SHOWED THAT TWO HINDBRAIN SEROTONERGIC NEURON POPULATIONS, THE DORSAL RAPHE NUCLEUS AND THE CAUDAL RAPHE NUCLEUS, DIFFERENTIALLY PROJECT TO THE SENSORY AND MOTOR REGIONS OF THE SPINAL CORD IN LARVAL ZEBRAFISH. WHETHER AND HOW THE ANATOMY OF THESE PROJECTIONS INFLUENCES SPINAL SEROTONIN RELEASE DURING NATURALISTIC BEHAVIOR, AND WHETHER SUCH RELEASE ALLOWS SENSORY AND MOTOR PROCESS TO BE MODULATED INDEPENDENTLY, HAS NOT BEEN STUDIED. IN THE EXPERIMENTS I OUTLINE IN THIS PROPOSAL, I WILL CHARACTERIZE THE ACTIVITY OF SEROTONERGIC RAPHE NEURONS DURING A VARIETY OF SENSORIMOTOR BEHAVIORS (AIM 1) AND DETERMINE WHETHER THIS ACTIVITY LEADS TO SPATIALLY PRECISE PATTERNS OF SEROTONIN RELEASE IN THE SPINAL CORD (AIM 2). I WILL ADDITIONALLY DETERMINE WHETHER DISTINCT RAPHE NUCLEI POPULATIONS ARE NECESSARY AND SUFFICIENT TO FACILITATE DIFFERENT ASPECTS OF SENSORY AND MOTOR BEHAVIORS THROUGH TRANSIENT OPTOGENETIC MANIPULATIONS (AIM 3). THESE EXPERIMENTS WILL REVEAL THE FUNCTIONAL ORGANIZATION OF THE NEURAL CIRCUITRY BY WHICH A SINGLE MODULATORY MOLECULE INTRICATELY CONTROLS ANIMAL BEHAVIOR IN AN EVER-CHANGING SENSORY ENVIRONMENT.