Neuropeptidergic regulation of sleep in C. elegans

 描述(申请人提供)：睡眠行为的时间由一个反馈环控制，该反馈环涉及“分子时钟”的基因表达。人们对这种生物钟如何调节睡眠行为知之甚少。这个项目的重点是了解计时机制如何在单一神经元分辨率下调节睡眠行为。我们使用线虫的嗜睡阶段作为睡眠的模型。嗜睡是一种静止状态，表现出与哺乳动物睡眠的行为和分子遗传相似之处。我们已经确定了一种名为NLP-22的睡眠诱导神经肽，它在一对神经元RIA中表达。我们将使用遗传学、光学和行为工具的组合来研究RIA神经元将定时分子信号与来自其他神经元的睡眠信号相结合的机制，以及它们最终如何影响外围靶器官。在目标1中，我们重点了解RIA神经元在睡眠调节中的作用。在目标2中，我们研究了NLP-22诱导摄食静止的机制。在目标3中，我们使用发现方法来识别新的催眠信号。我们的项目利用线虫强大的遗传和光学工具来阐明特定神经回路中睡眠调节的分子机制。

 DESCRIPTION (provided by applicant): The timing of sleep behavior is controlled by a feedback loop involving expression of genes of the `molecular clock'. How this clock regulates sleep behavior is poorly understood. This project is focused on understanding how the timing mechanism regulates sleep behavior at a single neuron resolution. We use the lethargus stage in the roundworm C. elegans as a model for sleep. Lethargus is a quiescent state that shows both behavioral and molecular genetic similarities to mammalian sleep. We have identified a sleep-inducing neuropeptide called NLP-22, which is expressed in one pair of neurons, the RIAs. We will use a combination of genetic, optical, and behavioral tools to study the mechanism by the RIA neurons integrate timing molecular signals with sleep signals from other neurons and how they ultimately affect peripheral target organs. In Aim 1, we focus on understanding the role of the RIA neurons in sleep regulation. In Aim 2, we investigate the mechanism by which NLP-22 induces feeding quiescence. And in Aim 3 we use a discovery approach to identify new somnogenic signals. Our project makes use of the powerful genetic and optical tools available in C. elegans to illuminate the molecular mechanism of sleep regulation within a defined neural circuit.