Neuropeptide modulation of behavior in C. elegans

描述（由申请人提供）：神经肽是神经元用于调节行为和生理的主要信号之一，神经肽受体是治疗疾病的重要治疗靶点。本研究探讨了线虫C.两个部分的优雅。在第一部分（具体目标1）中，我提出了一系列的实验，将阐明由血管催产素，一种新的C。哺乳动物神经肽加压素和催产素的直系同源物。这些实验的目的是定义一个神经肽能电路，调节行为的模式生物的最小组件。在第二部分（具体目标2和3），我描述了两种新的方法的发展，在蠕虫的神经肽信号的细胞特异性分析。第一种技术将能够阻断单个细胞内的所有神经肽产生（具体目标2），第二种技术将能够在成熟神经系统中的单个神经元内进行神经肽翻译的全基因组分析（具体目标3）。我进一步描述了我将如何应用这些技术来测试有关两个电路的假设，这两个电路被认为是利用神经肽信号，但特定的神经肽介质仍然是谜：AFD神经元的趋热性调节和ASI神经元的长寿调节。 公共卫生相关性：神经肽信号传导是调节生理和行为的重要机制，并且神经肽已经与从精神障碍到糖尿病的人类疾病相关联。我们的研究旨在揭示一种实验上易处理的模式生物C.优雅

DESCRIPTION (provided by applicant): Neuropeptides are one of the major signals that are used by neurons to modulate behavior and physiology, and neuropeptide receptors are important therapeutic targets for the treatment of disease. This proposal explores neuropeptide signaling in the nematode C. elegans in two parts. In the first part (Specific Aim 1), I propose a series of experiments that will elucidate the neural circuit regulated by vasotocin, a novel C. elegans ortholog of the mammalian neuropeptides vasopressin and oxytocin. These experiments aim to define the minimal components of a neuropeptidergic circuit that regulates behavior in a model organism. In the second part (Specific Aims 2 and 3), I describe the development of two new approaches for the cell-specific analysis of neuropeptide signaling in the worm. The first technique will enable the blockade of all neuropeptide production within a single cell (Specific Aim 2) and the second will enable the genome-wide profiling of neuropeptide translation within single neurons in the mature nervous system (Specific Aim 3). I further describe how I will apply these technologies to test hypotheses about two circuits that are believed to utilize neuropeptide signaling, but for which the specific neuropeptide mediators remain enigmatic: the regulation of thermotaxis by AFD neurons and the regulation of longevity by ASI neurons. PUBLIC HEALTH RELEVANCE: Neuropeptide signaling is an important mechanism that regulates physiology and behavior, and neuropeptides have been linked to human diseases ranging from psychiatric disorders to diabetes. Our studies aim to uncover the complex network of neurons and genes that control neuropeptide signaling in an experimentally tractable model organism, C. elegans.