Neuropeptide modulation of behavior in C. elegans

神经肽对线虫行为的调节

• 批准号: 8056554
• 负责人: Jennifer L Garrison
• 金额: $ 9万
• 依托单位: ROCKEFELLER UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8056554
• 关键词: Address; Adult; Animal Model; Behavior; Behavioral; Caenorhabditis elegans; Caloric Restriction; Cells; Complement; Complex; Development; Diabetes Mellitus; Disease; Endocrine; Enzymes; Genes; High temperature of physical object; Hormones; Individual; Link; Location; Longevity; Maps; Measures; Mediating; Mediator of activation protein; Mental disorders; Messenger RNA; Nematoda; Nervous system structure; Neurons; Neuropeptide Receptor; Neuropeptides; Orthologous Gene; Output; Oxytocin; Partner in relationship; Physiological; Physiology; Polyribosomes; Process; Production; Regulation; Relative (related person); Ribosomes; Series; Signal Transduction; Synapses; Techniques; Technology; Temperature; Testing; Translations; Vasopressins; Vasotocin; cold temperature; dietary restriction; genome-wide; human disease; neural circuit; novel; novel strategies; protein expression; public health relevance; receptor; research study; response; therapeutic target; transcription factor

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.

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。该提案分两部分探讨了线虫秀丽隐杆线虫中的神经肽信号传导。在第一部分（具体目标 1）中，我提出了一系列实验来阐明加压素（一种哺乳动物神经肽加压素和催产素的新型线虫直系同源物）调节的神经回路。这些实验旨在定义调节模型生物体行为的神经肽能回路的最小组成部分。在第二部分（具体目标 2 和 3）中，我描述了两种新方法的开发，用于对蠕虫中的神经肽信号传导进行细胞特异性分析。第一种技术将能够阻断单个细胞内所有神经肽的产生（具体目标 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（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关于两个回路的假设，这两个回路被认为利用神经肽信号传导，但具体的神经肽介质仍然是神秘的：AFD 神经元对趋热性的调节和 ASI 神经元对寿命的调节。 公共健康相关性：神经肽信号传导是调节生理和行为的重要机制，神经肽与从精神疾病到糖尿病等人类疾病有关。我们的研究旨在揭示在实验上易于处理的模型生物体——秀丽隐杆线虫中控制神经肽信号传导的神经元和基因的复杂网络。