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.

项目摘要也许“ Interoception”的最著名的例子是“肠感”。摊位会影响直觉，情感和认知；大脑可以调节食物摄入和消化。摊位包含其自己的肠神经系统，或肠道中的“小大脑”。它通过迷走神直接连接到中枢神经系统。迷走神经神经提供了双向 - 传入和有效的神经途径，可在摊位与大脑之间快速相互作用。摊位 - 维格斯 - 脑连接组对于人类健康至关重要，并且在功能障碍时具有重大的健康影响。但是，此连接组尚未详细映射或表征。目前尚不清楚大脑在何处以及如何根据其电节律，机械收缩和营养处理方法来调节摊位的功能。同样尚不清楚迷走神经如何从支架传递到大脑并将运动控制从大脑传达到胃中。为了填补这些空白，该项目的目的是表征大鼠摊位 - 脑部截距的中央和周围神经环节。对于中央组件，我们将在清醒动物中使用功能性磁共振成像来绘制中央胃网络，并表征其有关胃电节律，机械收缩和营养处理方面的活性和连通性。为了验证中央胃网络，我们将使用伪标记病毒和单纯疱疹病毒类型1使用神经解剖学跟踪。对于外围成分，我们将使用迷走神经和神经节电生理学来表征从支架到大脑的传入信号传导以及从大脑到支架的有效信号。为了阐明表演与大脑之间的因果关系，我们将使用细胞类型的特定化学遗传学来扰动中央胃网络，并评估对体形的影响，并使用迷走神经术来扰动该项目，该项目具有4个特定目的，以绘制中央胃网络（AIM 1），并与中央和近距离神经胃部循环效果，并将其描绘成胃部的神经胃循环。（AIM 2），运动性（AIM 3）和摄入养分（目标4）。为了实现这些目标，我们组成了一个合作和跨学科的专家团队，具有磁共振成像，胃肠病学，神经调节和电生理学方面的领先和互补专业知识。成功完成后，该项目将将尖端技术集成到一个独特的平台中，以全面评估中央功能和外围功能性神经元电路。作为直接结果，我们将在大鼠大脑中建立中央胃网络，解散其功能作用，并阐明因果关系而不是相关，这些结果将既有机械和技术基础，既可以更好地理解对停滞的brain式拦截及其对精神疾病的深刻含义（例如，压力和焦虑症（例如），evin和焦虑症（例如），evin（例如），evin evin（例如，evel），e。胃部疾病（例如功能性消化不良），以及脑和胃疾病的同时出现。