Functional mapping of efferent gut neuroepithelial circuits

传出肠道神经上皮回路的功能图谱

基本信息

批准号：
9301172
负责人：
Xiling Shen
金额：
$ 49.31万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-28 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9301172
关键词：
Abdomen Action Potentials Animal Model Animals Anorexia Autistic Disorder Bacteria Biomedical Engineering Books Brain Calcium Cell physiology Cells Clinical Colon Devices Diet Disease Eating Disorders Electric Wiring Enteral Enteroendocrine Cell Feeling Functional disorder Future Gastroenterology Glycoproteins Health Hormones Human Hypersensitivity Image Implant Intestinal Motility Irritable Bowel Syndrome Knowledge Life Maps Medicine Methods Molecular Nerve Neurobiology Neuroepithelial Neurons Neurophysiology - biologic function Nutrient Organ Peripheral Post-Traumatic Stress Disorders Process Public Health Rabies Rabies virus Research Personnel Sensory Signal Transduction Small Intestines Stimulus Stomach Stretching Sturnus vulgaris Surface Symptoms Synapses Taste Perception Technology Time Tongue Transgenic Mice United States National Institutes of Health Virus Visceral Work Writing brain pathway career cell motility chronic abdominal pain effective therapy experience fascinate gastrointestinal gastrointestinal function impression in vivo mid-career faculty mutant nerve supply neural circuit neuroregulation optogenetics pressure professor programs sensor sensory stimulus success therapy development tool vector

项目摘要

SUMMARY Since the times of Sir William Bayliss and Ernest Starling at the turn of the 20th century, the gut and the brain were thought to exchange sensory information only indirectly, through hormones. Using modern molecular tools, we recently uncovered a gut neuroepithelial circuit—analogous to that of taste cells in the tongue—formed by the innervation of sensory enteroendocrine cells. This peripheral neural circuit raise the possibility of understanding visceral hypersensitivity at the cellular level—a core symptom of several human disorders, including irritable bowel syndrome, chronic abdominal pain, and eating disorders. Enteroendocrine cells receive sensory stimuli from nutrients and bacteria in the gut lumen and respond by firing action potentials. Thus, this neuroepithelial suggests a path for gut sensory signals to modulate brain function and a receptacle for the brain to modulate gastrointestinal sensitivity. We formed an interdisciplinary team, with expertise in gut sensory neurobiology, biomedical engineering, and clinical gastroenterology, to define the brain-to-gut efferent function of this neuroepithelial circuit by taking advantage of newly developed animal models and in vivo technology. The focus on gastrointestinal chemosensory signaling has been afferent gut-to-brain pathways but the brain-to-gut efferent paths that modulate gastrointestinal sensitivity have been poorly described at best. In this Limited Competition - SPARC OT2 proposal, we focus on the efferent portion to produce foundational knowledge for future comprehensive mapping studies. We will pursue the following aims: 1. To map the vagal innervation of enteroendocrine cells in the small intestine. 2. To define the vagal modulation of the neuroepithelial circuit in vivo. By functionally mapping it, we envision developing a platform for future neuromodulation and dietary therapies to alleviate disorders of visceral sensory dysfunction.

概括自20世纪初威廉·贝利斯爵士（William Bayliss）和欧内斯特（Ernest Starling）时代以来，肠道和大脑被认为仅通过激素间接地交换感官信息。使用现代分子工具，我们最近发现了一个肠道神经上皮回路，这是舌头中味道细胞的含量，这是通过感觉肠内分泌细胞的神经形成的。这种周围神经元回路增加了了解细胞水平内脏超敏反应的可能性，这是几种人类疾病的核心症状，包括肠易激综合征，慢性腹痛和饮食失调。肠内分泌细胞从肠道内的营养和细菌中接受感觉刺激，并通过发射动作电位做出反应。该神经上皮提出了肠道感官信号调节脑功能的路径，并为大脑调节胃肠道敏感性的受体。我们组建了一个跨学科团队，拥有肠道神经生物学，生物医学工程和临床胃肠病学专家，通过利用新开发的动物模型和体内技术来定义该神经上皮电路的大脑对脑的有效功能。对胃肠道化学感觉信号的关注是传入的肠道到脑通道，但是调节胃肠道敏感性的大脑到牙齿的有效路径充其量最多可以描述。在这项有限的竞争中 - SPARC OT2提案，我们专注于为未来综合映射研究提供基础知识的有效部分。我们将追求以下目标： 1。绘制小肠中肠内分泌细胞的迷走神经支配。 2。定义体内神经上皮回路的迷走神经调节。通过在功能上绘制它，我们设想为未来的神经调节和饮食疗法开发一个平台，以减轻内脏感觉功能障碍的疾病。