Circadian regulation of brain and body in larval zebrafish

项目摘要 昼夜节律通过对细胞靶点的不同作用，彻底改变了动物的行为。 身体睡眠-活动周期的中断是影响行为、神经学、 新陈代谢和肌肉生理学。该提案提出了一系列旨在了解 生理节律对身体细胞和系统的影响机制和相互作用。昼夜节律 通过直接作用于目标以调节生理的信号分子在起搏器下游显现。 了解不同的目标是如何被修改，以实现一个星座的生理和行为 节律是时间生物学研究的主要目标。我们研究神经元、肌肉和生物力学 相互作用的幼体斑马鱼，一个听话的昼夜脊椎动物，我们的初步实验表明，这些动物 经历的昼夜节律变化的广度远比以前所知的更加多样化。虽然斑马鱼是一种 不完善的睡眠行为模型，其明确的昼夜节律结合其对生理的易驾驭性， 行为和遗传的方法使其成为了解昼夜节律如何组织的理想系统 并在细胞和器官间相互作用。我们建议定义不同的昼夜节律对神经系统的影响 通过跟踪和模拟斑马鱼的行为， 和觉醒的时间周期。我们将操纵光暴露解开昼夜节律和光效应 我们将使用计算模型来了解昼夜节律效应如何相互作用， 行为输出此外，我们将评估跨细胞生理的昼夜节律调节的广度， 通过进行体内电生理学和功能成像来靶向。将这种方法与细胞- 分辨率转录谱使我们能够定义昼夜节律效应分子如何在不同的细胞中发出不同的信号。 目标的最后，我们将通过检查局灶性病变后的节律来测试昼夜节律靶点之间的相互作用 整个神经系统。这些实验将提供详细的信息和模型 关于细胞和系统之间昼夜节律效应的相互作用。

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. We propose 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. We will manipulate light exposure to disentangle circadian and photic effects on target systems, and we will use computational models to understand how circadian effects interact to shape behavioral output. Furthermore, we will evaluate the breadth of circadian regulation of physiology across cellular targets by performing in vivo electrophysiology and functional imaging. Combining this approach with cellular- resolution transcriptional profiling enables us to define how circadian effector molecules signal divergently across targets. Finally, we will test for interactions across circadian targets by examining rhythms following focal lesions throughout the nervous system. Together these experiments will provide detailed information and models regarding the interaction of circadian effects across cells and systems.