Cellular and Circuit Mechanisms of Neuropeptide Signaling

神经肽信号转导的细胞和电路机制

• 批准号: 10404451
• 负责人: Jennifer L Garrison
• 金额: $ 38.8万
• 依托单位: BUCK INSTITUTE FOR RESEARCH ON AGING
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2022-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10404451
• 关键词: Anatomy; Animal Model; Anxiety Disorders; Behavior; Behavioral; Biochemical; Brain; Caenorhabditis elegans; Chemicals; Cognitive; Communication; Etiology; Exocytosis; Functional disorder; Glutamates; Goals; Language; Link; Mammals; Mediating; Medical; Mental Depression; Mental disorders; Monitor; Nervous system structure; Neuromodulator; Neurons; Neuropeptide Gene; Neuropeptides; Obesity; Organism; Output; Pathway interactions; Pharmaceutical Preparations; Physiology; Research; Schizophrenia; Signal Transduction; Synapses; Time; addiction; autism spectrum disorder; behavior influence; chemical release; drug of abuse; fast-acting neurotransmitter; gamma-Aminobutyric Acid; insight; millisecond; neural circuit; neuropsychiatry; neuroregulation; new therapeutic target; parent grant; parent project; tool

Parent Project Summary The functions of the brain emerge from communication between neurons. The language of neuronal communication is mediated by chemicals that are released from one neuron and sensed by another. These chemical signals consistent of both classical “fast acting” neurotransmitters such as glutamate and GABA that signal across synapses in milliseconds, as well as more than 100 diverse neuromodulators that act on longer timescales. Neuromodulators are the major targets of most neuropsychiatric drugs as well as drugs of abuse, and their dysregulation is implicated in medical conditions ranging from obesity to psychiatric disorders. Yet we still lack a clear understanding, at both the cellular and neural circuit level, of how these neuromodulators and their fast acting counterparts cooperate to generate the diverse behavioral outputs of the brain. Neuropeptides are the largest and most diverse class of neuromodulators that neurons use to communicate with each other and regulate behavior. Yet we know little about the general rules that govern and constrain neuromodulatory signaling in any organism. Here I propose to use the compact nervous system of C. elegans as a unique paradigm to link neuropeptide signaling and neural circuits in a whole animal model. Despite its anatomical simplicity, C. elegans makes rich use of neuropeptide signaling to regulate its behavior and physiology and in shares a similar number of neuropeptide genes with mammals and a conserved set of enzymatic pathways that regulate neuropeptide synthesis, processing, transport, and exocytosis. Our goal is to discover, for the first time, how the biochemical network of neuromodulators relates to the fixed anatomy of the brain in a whole animal model. Understanding this relationship is key to develop tools to monitor brain activity, and ultimately to discover treatments for cognitive and behavioral dysfunction. We will continue to pursue the parent grant project goals during the supplement period.

父项目摘要 大脑的功能来自神经元之间的通信。神经元语言 通信是由从一个神经元释放并被另一种神经感应的化学物质介导的。 这些化学信号在两个经典的“快速作用”神经递质（例如谷氨酸）一致 和GABA，以毫秒为单位的突触以及100多个潜水员发出信号 对较长时间尺度作用的神经调节剂。神经调节剂是大多数的主要目标 神经精神药物和滥用药物及其失调在医学中暗示 从肥胖到精神疾病的状况。然而，我们仍然缺乏清晰的理解 这些神经调节剂及其快速起作用的细胞和神经回路水平 合作以产生大脑的不同行为输出。神经肽是最大的， 神经元用来相互交流并调节的大多数潜水员类的神经调节剂类 行为。然而，我们对管理和限制神经调节的一般规则一无所知 在任何组织中发出信号。在这里，我建议将秀丽隐杆线虫的紧凑神经系统用作 在整个动物模型中，独特的范式连接神经肽信号传导和神经回路。尽管有它 解剖学简单，秀丽隐杆线虫丰富地利用神经肽信号传导来调节其行为和 生理学和与哺乳动物和保守集的神经肽基因相似 调节神经肽合成，加工，转运和胞吐作用的酶促途径。我们的 目标是第一次发现神经调节剂的生化网络与 修复了整个动物模型中大脑的解剖结构。了解这种关系是发展的关键 监视大脑活动的工具，并最终发现认知和行为的治疗方法 功能障碍。在补充期间，我们将继续追求父母赠款项目目标。