Functional Neural Circuits of Stomach-Brain Interoception

胃脑内感受的功能神经回路

基本信息

批准号：
10698021
负责人：
Jiande Chen
金额：
$ 56.5万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-01 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10698021
关键词：
Address Affect Animals Anxiety Brain Brain Mapping Brain region Carbohydrates Central Nervous System Chemicals Cognition Complex Coupled Coupling Digestion Disease Dorsal Dyspepsia Eating Efferent Neurons Electrophysiology (science)Emotions Enteric Nervous System Fasting Fatty acid glycerol esters Feeling Food Foundations Functional Magnetic Resonance Imaging Functional disorder Gastroenterology Genetic Health Herpesvirus 1 Homeostasis Human Inflammatory Infusion procedures Ingestion Interoception Intuition Knowledge Magnetic Resonance Imaging Maps Mechanics Mediating Mental disorders Migrating Myoelectric Complex Monitor Nerve Neural Pathways Neuroanatomy Neurologic Nodose Ganglion Nutrient Outcome Parkinson Disease Peripheral Proteins Rattus Reflex action Regulation Rest Role Sensory Signal Transduction Stomach Stress Technology Testing Vagotomy Vagus nerve structure Viscera awake cell motility cell type connectome mad itch virus mind control motor control nervous system disorder neural circuit neuroregulation neurotransmission pharmacologic pressure

项目摘要

Project Summary Perhaps the most notable example of “interoception” is the “gut feeling”. The stomach can affect intuition, emotion and cognition; the brain can regulate food ingestion and digestion. The stomach contains its own enteric nervous system, or the “little brain” in the gut. It connects directly to the central nervous system via the vagus. The vagus nerves provide a bi-directional – afferent and efferent – neural pathway for rapid interactions between the stomach and the brain. The stomach-vagus-brain connectome is central to human health and has significant health implications at dysfunction. However, this connectome has not been mapped or characterized in detail. It is unclear where and how the brain monitors and regulates the function of the stomach in terms of its electrical rhythm, mechanical contraction, and nutrient handling. It is also not exactly clear how the vagus nerves relay sensory information from the stomach to the brain and convey motor control from the brain to the stomach. To fill these gaps, this project is aimed to characterize the central and peripheral neural circuits of stomach-brain interoception in rats. For the central component, we will use functional magnetic resonance imaging in awake animals to map the central gastric network and characterize its activity and connectivity with respect to gastric electrical rhythm, mechanical contraction, and nutrient handling. To verify the central gastric network, we will use neuroanatomical tracing with pseudorabies virus and herpes simplex virus type-1. For the peripheral component, we will use the vagus nerve and nodose ganglion electrophysiology to characterize the afferent signaling from the stomach to the brain and the efferent signaling from the brain to the stomach. To elucidate the causal interaction between the stomach and the brain, we will use cell-type specific chemogenetics to perturb the central gastric network and assess the resulting effect on the stomach and use vagotomy to perturb the vagal circuitry and assess the resulting effect on the brain. This project has 4 specific aims for mapping the central gastric network (Aim 1) and characterizing the central and peripheral neural circuits for stomach-brain interoception related to gastric electrophysiology (Aim 2), motility (Aim 3), and ingestion of nutrients (Aim 4). To accomplish these aims, we form a collaborative and interdisciplinary team of experts with leading and complementary expertise in magnetic resonance imaging, gastroenterology, neuromodulation and electrophysiology. Upon its successful completion, this project will have integrated cutting-edge technologies into a unique platform for comprehensive assessment of the central and peripheral functional neural circuits underlying stomach-brain interoception. As the immediate outcome, we will have established the central gastric network in the rat brain, disentangled its functional roles, and elucidated the causal, rather than correlational, interactions between the stomach and the brain. These outcomes will lay both mechanistic and technical foundations for better understanding of stomach-brain interoception and its profound implications to mental illnesses (e.g., stress and anxiety), neurological disorders (e.g., Parkinson’s diseases) and gastric disorders (e.g., functional dyspepsia), and the co-occurrence of both brain and gastric disorders.

项目概要也许“内感受”最显着的例子是“肠道感觉”；大脑可以调节食物的摄入和消化。胃有自己的肠神经系统，或者说“小大脑”。它通过迷走神经直接连接到中枢神经系统，为胃和大脑之间的快速相互作用提供双向（传入和传出）神经通路。然而，这种连接组对于人类健康至关重要，并且对功能障碍具有重要的健康影响，但目前尚不清楚大脑在何处以及如何在电节律、机械方面监测和调节胃的功能。目前还不清楚迷走神经如何将感觉信息从胃传递到大脑，并将运动控制从大脑传递到胃。胃脑周围神经回路对于大鼠的内感受，我们将使用清醒动物的功能磁共振成像来绘制中央胃网络，并表征其在胃电节律、机械收缩和营养处理方面的活动和连接性，以验证中央胃网络。在网络中，我们将使用伪狂犬病病毒和 1 型单纯疱疹病毒进行神经解剖学追踪。对于外周成分，我们将使用迷走神经和结状神经节电生理学来表征从胃到大脑的传入信号。为了阐明胃和大脑之间的因果相互作用，我们将使用细胞类型特异性化学遗传学来扰乱中央胃网络并评估对胃的影响，并使用迷走神经切断术来扰乱胃。该项目有 4 个具体目标，即绘制中央胃网络（目标 1）并表征与胃相关的胃脑内感受的中枢和外周神经回路。电生理学（目标 2）、运动性（目标 3）和营养物质摄入（目标 4）为了实现这些目标，我们组建了一个协作和跨学科的专家团队，他们在磁共振成像、胃肠病学、神经调节和电生理学方面拥有领先和互补的专业知识。成功完成后，该项目将把尖端技术集成到一个独特的平台中，以全面评估胃脑内感受的中枢和外周功能神经回路。研究人员对大鼠大脑中的中央胃网络进行了研究，阐明了其功能作用，并阐明了胃与大脑之间的因果关系，而不是相关性，这些结果将为更好地理解胃-脑内感受及其相关性奠定机制和技术基础。对精神疾病（例如压力和焦虑）、神经系统疾病（例如帕金森病）和胃病（例如功能性消化不良）以及两者同时发生的广泛影响大脑和胃部疾病。