Neuropeptide modulation of behavior in C. elegans

项目摘要/摘要 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靶点。这项建议 分两部分探讨线虫体内的神经肽信号。在第一部分(具体目标1)中，我 提出一系列实验来阐明一种新的线虫--血管催产素对神经回路的调节 哺乳动物神经肽血管加压素和催产素的同源基因。这些实验的目的是定义 在模式生物中调节行为的神经肽能回路的最小组成部分。在第二个 部分(具体目标2和3)，我描述了用于细胞特异性分析的两种新方法的发展 蠕虫体内的神经肽信号。第一种技术将能够阻断所有神经肽的产生 在单个细胞内(特定目标2)，第二个将实现神经肽的全基因组图谱 成熟神经系统中单个神经元内的翻译(特定目标3)。我会进一步描述我将如何 应用这些技术来测试关于两个据信利用神经肽的回路的假说 信号，但特定的神经肽介体对其仍是谜：通过 AFD神经元和ASI神经元对寿命的调节。

Project Summary/Abstract 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.