Neuropeptidergic regulation of sleep in C. elegans

线虫睡眠的神经肽调节

• 批准号: 9011550
• 负责人: David Menassah Raizen
• 金额: $ 34.74万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-15 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9011550
• 关键词: Affect; Aging; Animal Model; Animals; Behavior; Behavioral; Behavioral Genetics; Biological; Caenorhabditis elegans; Calcium; Cell Death; Cells; Clinic; Clock protein; Communication; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Diagnosis; Diagnostic; Drosophila genus; Feedback; Figs - dietary; G-Protein-Coupled Receptors; Gene Expression; Genes; Genetic; Genetic Screening; Genome; Goals; Health; Human; Image; Interneurons; Knock-out; Laboratories; Lobular Neoplasia; Mammals; Messenger RNA; Modeling; Molecular; Molecular Genetics; Molecular Target; Mus; Nematoda; Nervous system structure; Neurons; Neuropeptide Receptor; Neuropeptides; Neurosecretory Systems; Optics; Organ; Outcome; Pathway interactions; Pattern; Peptide Signal Sequences; Peripheral; Pharyngeal structure; Process; RNA Interference; Regulation; Research; Resolution; Role; Signal Transduction; Sleep; Sleep Disorders; Staging; Testing; Time; Tissues; Transgenic Organisms; Translating; Translations; Work; base; feeding; genetic manipulation; improved; knock-down; neural circuit; optogenetics; overexpression; pharynx muscle; programs; receptor; research study; response; sleep regulation; therapeutic target; tool

 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.

 描述（适用提供）：睡眠行为的时机由反馈回路控制，涉及“分子钟”的基因表达。该时钟如何调节睡眠行为的理解很少。该项目的重点是了解定时机制如何以单个神经元分辨率调节睡眠行为。我们在round虫C.秀丽隐杆线虫中使用Lethargus阶段作为睡眠模型。莱萨尔古斯（Lethargus）是一个静止状态，表现出与哺乳动物睡眠的行为和分子遗传相似性。我们已经确定了一种名为NLP-22的睡眠诱导的神经肽，该神经肽在一对神经元中表达。我们将使用遗传，光学和行为工具的组合来研究RIA神经元与其他神经元的睡眠信号的RIA神经元的机制，以及它们最终如何影响外围目标器官。在AIM 1中，我们专注于理解RIA神经元在睡眠调节中的作用。在AIM 2中，我们研究了NLP-22进食静止的机制。在AIM 3中，我们使用发现方法来识别新的女性信号。我们的项目利用秀丽隐杆线虫中可用的强大遗传和光学工具来阐明定义的神经元回路中睡眠调节的分子机制。