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.