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The efferent synapse in enteroendocrine cells

肠内分泌细胞中的传出突触

基本信息

批准号：
10018637
负责人：
Diego V Bohorquez
金额：
$ 20.13万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-16 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10018637
关键词：
Action Potentials Afferent Neurons Bacteria Behavior Behavior Disorders Behavioral Biological Assay Brain Brain Stem Calcium Cell physiology Cells Coculture Techniques Collaborations Colon Data Desire for food Disease Drug Design Efferent Neurons Electrophysiology (science)Enteroendocrine Cell Epithelial Cells Face Feedback Fire - disasters Foundations Functional disorder Gastrointestinal Diseases Gastrointestinal tract structure Glutamates Goals Human Hypersensitivity Image In Vitro Inner Hair Cells Intestines Irritable Bowel Syndrome Laboratories Link Mucous Membrane Mus Nerve Neurons Neurotransmitters Norepinephrine Nutrient Organoids Outcome Pain Peptide YY Perception Peripheral Peripheral Nerves Pharmacology Public Health Rabies virus Research Research Project Grants Rewards Sacral nerve Scaffolding Protein Science Sensory Sensory Process Serotonin Signal Transduction Spinal Spinal Cord Spinal Ganglia Stimulus Stress Synapses Synaptic Transmission System Taste Buds Tissues United States National Institutes of Health Vagus nerve structure Virus Visceral Work density effective therapy fascinate gastrointestinal gastrointestinal function human imaging in vivo millisecond nerve supply neural circuit programs receptor relating to nervous system sensory input side effect success sugar targeted treatment therapeutic target two-photon

项目摘要

ABSTRACT Today, there is a fascination with gut-to-brain sensory transduction. Nutrients and bacteria are known to modulate behaviors. However, how the brain modulates gastrointestinal sensory function is unknown. Several behavioral disorders, such as those related to stress and appetite, have been linked with altered visceral function. The pillars of sensory transduction in the gut are the neurons that innervate the mucosa and the enteroendocrine cells — epithelial cells that face the lumen. When stimulated by nutrients, or bacteria, they fire action potentials. We recently discovered that these cells synapse with the vagus nerve to transduce nutrient stimuli to the brain in milliseconds. They do so using glutamate as a neurotransmitter. Recent studies have also shown that a subset of enteroendocrine cells that secrete serotonin are activated by the sympathetic neurotransmitter, norepinephrine. Our preliminary data show that these cells also receive synaptic inputs from peripheral neurons of the spinal cord. Therefore, we hypothesize that spinal neurons use norepinephrine as an efferent neurotransmitter to modulate enteroendocrine cell sensory function. With the support of this NIH R21 research project, our goal is to dissect this neural circuit by 1) defining the efferent synapse both in vivo and in vitro; and 2) establishing norepinephrine as an efferent neuron-to-enteroendocrine cell synaptic neurotransmitter. This project will set the neural basis for understanding how brain function and behaviors alter visceral sensory function.

摘要