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 世纪之交威廉·贝利斯爵士和欧内斯特·斯塔林时代以来，人们认为肠道和大脑只能通过激素间接交换感觉信息，最近我们利用现代分子工具发现了类似于肠道神经上皮回路。舌头中的味觉细胞由感觉肠内分泌细胞的神经支配形成，这种周围神经回路提高了在细胞水平上理解内脏过敏的可能性，这是内脏过敏的核心症状。多种人类疾病，包括肠易激综合症、腹部慢性疼痛和饮食失调。肠内分泌细胞接收来自肠腔中的营养物和细菌的感觉刺激，并通过激发动作电位做出反应，因此，这种神经上皮表明了肠道感觉信号调节大脑功能的途径和大脑调节胃肠道敏感性的容器。该团队拥有肠道感觉神经生物学、生物医学工程和临床胃肠病学方面的专业知识，通过利用新开发的动物模型和体内技术。胃肠道化学感应信号传导的重点是传入的肠道到大脑的通路，但调节胃肠道敏感性的大脑到肠道的传出路径最多被描述得很少。在这个有限的竞赛 - SPARC OT2 提案中，我们重点关注传出部分。为未来的综合测绘研究提供基础知识，我们将追求以下目标： 1. 绘制小肠肠内分泌细胞的迷走神经支配图。 2. 定义体内神经上皮回路的迷走神经调节。通过对其进行功能映射，我们设想开发一个未来神经调节和饮食疗法的平台，以减轻内脏感觉功能障碍。