Circadian regulation of brain and body in larval zebrafish

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Project Summary Circadian rhythms drastically alter animal behavior through diverse actions on cellular targets throughout the body. Disruptions of sleep-activity cycles account for a wide range of diseases affecting behavior, neurology, metabolism, and muscle physiology. This proposal presents a set of studies designed to understand the mechanisms and interactions of circadian effects on cells and systems spanning the body. Circadian rhythms manifest downstream of pacemakers via signaling molecules that act directly on targets to regulate physiology. Understanding how distinct targets are modified to achieve a constellation of physiological and behavioral rhythms is a major goal in chronobiological research. We study how neurons, muscles, and biomechanics interact in larval zebrafish, a tractable diurnal vertebrate, and our preliminary experiments suggest these animals experience a breadth of circadian changes far more diverse than previously known. Although the zebrafish is an imperfect model of sleep behavior, its clear circadian rhythms combined with its tractability for physiological, behavioral, and genetic approaches make it an ideal system for understanding how circadian rhythms organize and interact across cells and organs. The original proposal aims to define how diverse circadian effects on nervous system output and muscle physiology amount to complex behavioral output, by tracking and modeling zebrafish behavior and arousal across the diel cycle. Here we request resources to complement institutional support for a multiphoton microscope, which affords activity measurements using invisible light, thereby facilitating comparisons of physiology across circadian time without the confounding effects of measurement approaches that use visible light. Together these experiments will provide detailed information and models regarding the interaction of circadian effects across cells and systems.