Studies of behavioral quiescence in C. elegans

描述（由申请人提供）：我们对行为静止状态（如睡眠）及其与发育的关系的理解受到阻碍，因为缺乏具有良好解剖结构的动物模型，以及对静止状态进行遗传分析的强大工具。秀丽隐杆线虫是一种遗传上易于控制的动物，具有非常好理解的神经解剖学，并已被用于模拟人类疾病相关的几个过程。静止状态发生在嗜睡期间，这是一个发育控制的时期，在此期间神经系统中有广泛的突触发生。首席研究员雷曾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。具体来说，他将测试血清素、多巴胺和腺苷在静止状态控制中的作用，并描述这种状态的稳态控制。在Aim 2中，他将验证一种假设，即秀丽隐杆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作用。在Aim 3中，他将确定在发育过程中突触发生是否需要静息。这些研究将比较和对比秀丽隐杆线虫的行为静止与其他动物的行为静止，并将回答这个问题：秀丽隐杆线虫的静止是否可以被认为是一种类似睡眠的状态？无论答案是什么，这项研究都将解决行为状态控制及其与神经系统变化的关系中的基本问题。这些研究将在睡眠和神经生物学中心的Allan Pack博士和遗传学系的Meera Sundaram博士的实验室进行。这笔培训经费将支持Raizen博士学习睡眠和时间生物学的科学领域，并将秀丽隐杆线虫作为研究行为静止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.