Cellular and Circuit Mechanisms of Neuropeptide Signaling

父项目摘要 大脑的功能来自神经元之间的交流。神经元的语言 交流是由一个神经元释放的化学物质和另一个神经元感受到的化学物质介导的。 这些化学信号与经典的“快速作用”神经递质如谷氨酸 和GABA，在毫秒内通过突触传递信号，以及100多种不同的 作用时间更长的神经调质。神经调质是大多数神经递质的主要靶点。 神经精神药物以及滥用药物，它们的失调与医疗保健有关。 从肥胖症到精神疾病。然而，我们仍然缺乏一个清晰的认识，在这两个 细胞和神经回路水平，这些神经调质和它们快速作用的对应物 合作产生大脑的各种行为输出。神经肽是最大的， 神经元用来相互交流和调节的最多样化的神经调质 行为然而，我们对控制和限制神经调节的一般规则知之甚少。 任何生物体中的信号。在这里，我建议使用C的紧凑的神经系统。优雅作为一个 在整个动物模型中连接神经肽信号和神经回路的独特范例。尽管 解剖简单性C.线虫利用神经肽信号调节其行为， 在生理学上，它与哺乳动物有着相似数量的神经肽基因， 调节神经肽合成、加工、运输和胞吐作用的酶途径。我们 目标是首次发现神经调质的生物化学网络如何与神经元相互作用。 在一个完整的动物模型中固定大脑的解剖结构。理解这种关系是发展的关键 工具来监测大脑活动，并最终发现治疗认知和行为 功能障碍我们将在补充期间继续追求父母补助金项目的目标。

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.