Neuropeptidergic regulation of sleep in C. elegans

线虫睡眠的神经肽调节

基本信息

批准号：
8884123
负责人：
David Menassah Raizen
金额：
$ 34.1万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
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/8884123
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 Receptor Genes G-Protein-Coupled Receptors Gene Expression Genes Genetic Genetic Screening Genome Goals 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 pharynx muscle programs public health relevance receptor research study response sleep regulation therapeutic target tool

项目摘要

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”基因表达的反馈环路控制。该项目如何调节睡眠行为目前还知之甚少。我们使用线虫的昏睡阶段作为睡眠模型，它显示出与哺乳动物睡眠的行为和分子遗传相似性。一种称为 NLP-22 的睡眠诱导神经肽，在一对神经元（RIA）中表达。我们将结合遗传、光学和行为工具来研究 RIA 神经元将定时分子信号与睡眠信号整合的机制。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 诱导进食静止的机制。 3 我们使用一种发现方法来识别新的催眠信号。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特定神经回路内睡眠调节的分子机制。