Sensory receptors of the vagus nerve

项目摘要 初级感官感受器的发现，它调节我们的外部嗅觉、触觉、味觉和 愿景是里程碑式的成就。相比之下，迷走神经的内部感觉系统 在分子水平上研究不足，主要感觉受体在任何器官系统中都是未知的。这个 迷走神经是大脑和身体之间控制摄食行为、呼吸、血液的主要管道。 血压、新陈代谢、心率、恶心和咳嗽。机械感觉和化学感觉转导 迷走神经的机制在感觉生物学中是非常重要的问题。感官 检测进餐引起的胃胀、主动脉弓血压、肺扩张的受体 在呼吸过程中，引起咳嗽的刺激物或引起恶心的化疗药物是未知的。 在分子水平上了解迷走神经信号如何与广泛的临床相关 病症包括肥胖、糖尿病、结肠炎、哮喘、恶心、抑郁和癫痫。 这个项目的目标是识别迷走神经的主要感觉受体， 器官状态。最初的努力将集中在寻找胃和肺机械感受器以及主动脉 压力感受器，工作可以扩大到识别刺激和毒素受体，引起咳嗽和 恶心。迷走神经机械感受器将使用一种新的活体神经节成像方法进行识别 允许分析单个神经元对内部器官刺激的反应。活体神经节成像是 与用于基因功能分析的嵌合体功能丧失方法(如RNAi)兼容。 解构迷走神经传入的感觉生物学将揭示如何自主的基本见解 生理学是由神经系统控制的，可能为治疗设计提供新的机会。 这一建议建立在多年的基础工作基础上，传统资金无法支持 由于项目范围大，与受体识别研究相关的风险，以及 我在这个新领域的有限出版记录。到目前为止，我们在这个系统中的早期工作具有 不同生理系统中的感觉神经元类型(Cell，2015)。资金将使新的 分子水平的努力，以确定主要的感觉受体蛋白，检测内部感觉线索。

Project Summary The discoveries of primary sensory receptors that mediate our external senses of smell, touch, taste, and vision were landmark achievements. In contrast, internal sensory systems of the vagus nerve are vastly understudied at a molecular level, with primary sensory receptors unknown in any organ system. The vagus nerve is a major conduit between brain and body that controls feeding behavior, respiration, blood pressure, metabolism, heart rate, nausea, and cough. Mechanosensory and chemosensory transduction mechanisms in the vagus nerve present tremendously important problems in sensory biology. Sensory receptors that detect meal-induced stomach distension, blood pressure at the aortic arch, lung expansion during breathing, irritants that cause cough, or chemotherapeutics that induce nausea are unknown. Understanding how the vagus nerve signals at a molecular level is relevant for a wide range of clinical conditions, including obesity, diabetes, colitis, asthma, nausea, depression, and epilepsy. The goals of this project are to identify primary sensory receptors of the vagus nerve that survey internal organ state. Initial efforts will focus on finding stomach and lung mechanoreceptors as well as aortic baroreceptors, and work could be extended to identify irritant and toxin receptors that evoke cough and nausea. Vagal mechanoreceptors will be identified using a novel in vivo ganglion imaging approach that permits analysis of single neuron responses to internal organ stimuli. In vivo ganglion imaging is compatible with mosaic loss-of-function approaches like RNAi for analysis of gene function. Deconstructing the sensory biology of vagal afferents will reveal basic insights into how autonomic physiology is controlled by the nervous system, and may provide new opportunities for therapy design. This proposal builds on years of foundational work, and is not supportable by traditional funding mechanisms due to the large project scope, the risk associated with receptor-identification studies, and my limited publication record in this new field. So far, our early work in this system has characterized sensory neuron types in different physiological systems (Cell, 2015). Funding would enable new molecular-level efforts to identify primary sensory receptor proteins that detect internal sensory cues.