Neuropeptide modulation of behavior in C. elegans

描述（申请人提供）：神经肽是神经元用来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。本研究分两部分探讨了秀丽隐杆线虫的神经肽信号。在第一部分（Specific Aim 1）中，我提出了一系列的实验来阐明由血管催产素调节的神经回路，血管催产素是一种新型的秀丽隐杆线虫神经肽，与哺乳动物神经肽血管加压素和催产素同源。这些实验旨在确定调节模式生物行为的神经肽能回路的最小组成部分。在第二部分（Specific Aims 2和3）中，我描述了两种新方法的发展，用于蠕虫中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所有神经肽的产生（Specific Aim 2），第二种技术将能够对成熟神经系统中单个神经元内的神经肽翻译进行全基因组分析（Specific Aim 3）。我进一步描述了我将如何应用这些技术来测试关于两个回路的假设，这两个回路被认为是利用神经肽信号，但具体的神经肽介质仍然是谜：由AFD神经元调节热致性和由ASI神经元调节寿命。

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.