Neuropeptidergic regulation of sleep in C. elegans

线虫睡眠的神经肽调节

• 批准号: 9312998
• 负责人: David Menassah Raizen
• 金额: $ 4.82万
• 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: 2015-07-01 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9312998
• 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（由申请人提供）：睡眠行为的时间由涉及“分子钟”基因表达的反馈回路控制。这种生物钟如何调节睡眠行为还知之甚少。该项目的重点是了解计时机制如何在单个神经元分辨率下调节睡眠行为。我们使用线虫C的昏睡期。elegans优雅as a model模型for sleep睡眠.昏睡是一种静止状态，表现出与哺乳动物睡眠的行为和分子遗传相似性。我们已经确定了一种称为NLP-22的睡眠诱导神经肽，它在一对神经元中表达，RIA。我们将使用遗传，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其他神经元的睡眠信号整合的机制，以及它们最终如何影响外周靶器官。在目标1中，我们专注于了解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致眠信号。我们的项目利用了C语言中强大的遗传和光学工具。elegans阐明睡眠调节的分子机制在一个明确的神经回路。