Identifying vagal sensory neurons responsible for chemosensation in the gut

项目摘要/摘要 通过迷走神经的化学感觉信号是肠道-脑轴的重要组成部分， 传递有关肠腔内营养物质和刺激物存在的信息。迷走神经感觉 神经元将这些信号从肠道传递到脑干，激活神经电路来调节 消化，或引发呕吐或腹泻。虽然这种电路的生理学已经研究了几十年， 直到最近，受体、细胞和信号机制的分子细节才开始被确定。 开创性的工作已经确定了两种特定的迷走神经感觉神经元群体，它们在 信号在胃中伸展，营养在十二指肠中。这表明迷走神经可以 用标记线的方式编码感官信息，即一行代表拉伸，一行代表营养。除了 这两个特定的迷走神经感觉群支配肠道，其他神经元群负责 刺激感觉，或十二指肠/近端肠外的营养感觉仍未确定。基本信息 有关支配肠道的迷走感觉神经元及其信息类型的信息 编码是缺乏的。这项提议的目标是定义检测营养物质和 肠道中的刺激物：1)肠道营养和刺激性信息是如何编码的 通过迷走感觉神经元？2)活动依赖的标记技术是否可以用于电路标测和 迷走神经感觉神经元功能亚群的分子特征？

PROJECT SUMMARY/ABSTRACT Chemosensory signaling through the vagus nerve is an important component of the gut-brain axis, relaying information about the presence of nutrients and irritants within the lumen of the gut. Vagal sensory neurons transmit these signals from the gut to the brainstem, activating neural circuits to modulate the rate of digestion, or trigger emesis or diarrhea. Although the physiology of this circuit has been studied for decades, only recently have the molecular details of the receptors, cells, and signaling mechanisms begun to be defined. Pioneering work has identified two specific populations of vagal sensory neurons that play distinct roles for signaling stretch in the stomach and nutrients in the duodenum. This demonstrates that vagal neurons can encode sensory information in a labeled-line fashion, ie one line for stretch, one line for nutrients. Apart from these two specific vagal sensory populations innervating the gut, other populations of neurons responsible for irritant sensing, or nutrient sensing outside of the duodenum/proximal intestine remain undefined. Basic information about the repertoire of vagal sensory neurons innervating the gut and the types of information they encode are lacking. The goal of this proposal is to define the chemosensory circuits for detecting nutrients and irritants in the gut by addressing the following questions: 1) How is gut nutrient and irritant information encoded by vagal sensory neurons? 2) Can activity dependent labeling techniques be used for circuit mapping and molecular characterization of functional subsets of vagal sensory neurons?