Studies of behavioral quiescence in C. elegans

描述(申请人提供)：阻碍我们理解睡眠等行为静止状态及其与发育的关系的原因是，除了用于静止的基因分析的强大工具外，缺乏具有良好解剖学基础的动物模型。秀丽隐杆线虫是一种遗传上易驯化的动物，具有精致的神经解剖学，已被用来模拟几个与人类疾病相关的过程。静止状态发生在昏睡期，这是一个发育受控的时期，在此期间神经系统有广泛的突触发生。首席研究员Raizen博士计划研究控制这种静止状态的时间和执行的过程和神经化学物质。具体地说，他将测试5-羟色胺、多巴胺和腺苷在控制静止状态中的作用，并表征这种状态的稳态控制。在目标2中，他将检验这样一种假设，即线虫与昼夜节律蛋白周期同源的Lin-42蛋白在控制静止时间方面发挥了作用。在目标3中，他将确定在发育过程中是否需要静止来进行突触发生。这些研究将比较和对比线虫和其他动物的行为静止，并回答这个问题：线虫的静止可以被认为是一种类似睡眠的状态吗？无论答案如何，这项研究都将解决行为状态控制的基本问题及其与神经系统变化的关系。这些研究将在睡眠和神经生物学中心的艾伦·帕克博士的实验室和遗传学系的米拉·孙达拉姆博士的实验室进行。这笔培训拨款将支持Raizen博士学习睡眠和时间生物学的科学领域，并开发线虫作为研究行为静默及其与发育关系的模型系统。

DESCRIPTION (provided by applicant): Impeding our understanding of behaviorally quiescent states such as sleep and their relationship to development is a lack of an animal model that has a well-understood anatomy in addition to powerful tools for genetic analysis of quiescence. Caenorhabditis elegans is a genetically tractable animal with an exquisitely well-understood neuroanatomy and has been used to model several processes of human disease relevance. A quiescent state occurs during lethargus, a developmentally controlled period during which there is extensive synaptogenesis in the nervous system. Dr. Raizen, the principal investigator, plans to investigate the processes and neurochemicals that control the timing and execution of this quiescent state. Specifically, he will test the roles of serotonin, dopamine, and adenosine in the control of quiescence and characterize the homeostatic control of this state. In Aim 2, he will test the hypothesis that the LIN-42 protein, the C. elegans orthologue to the circadian protein PERIOD, plays a role in the control of the timing of quiescence. In Aim 3, he will determine whether or not quiescence is required for synaptogenesis during development. These studies will compare and contrast behavioral quiescence in C. elegans to that seen in other animals and will answer the question: Can quiescence in C. elegans be considered a sleep like state? Regardless of the answer, the study will address fundamental problems in behavioral state control and its relationship to nervous system change. The studies will be performed in the laboratories of Dr. Allan Pack in the Center for Sleep and Neurobiology, and of Dr. Meera Sundaram, in the Department of Genetics. This training grant will support Dr. Raizen while he learns the scientific field of sleep and chronobiology and develops C. elegans as a model system for the study of behavioral quiescence and its relationship to development.