Dissecting Viscerosensory Pathways Controlling Feeding Behavior

剖析控制进食行为的内脏感觉通路

• 批准号: 10226798
• 负责人: Carlos A Campos
• 金额: $ 14.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10226798
• 关键词: Ablation; Affective; Afferent Neurons; Afferent Pathways; Area; Behavior; Behavior Control; Brain; Calcitonin Gene-Related Peptide; Cardiovascular Diseases; Cells; Chemicals; Chronic; Clinical; Complex; Consumption; Cre driver; Data; Desire for food; Devices; Dissection; Dorsal; Eating; Endocrine; Excision; Feeding behaviors; Feeling; Future; Gastrointestinal tract structure; Goals; Health; Homeostasis; Hunger; Implant; Lead; Learning; Link; Molecular Genetics; Mus; Nausea; Neurons; Neuropeptides; Non-Insulin-Dependent Diabetes Mellitus; Obese Mice; Obesity; Operant Conditioning; Operative Surgical Procedures; Opsin; Organ Specificity; Pathway interactions; Peripheral; Physiological; Physiology; Population; Reflex action; Regulation; Reporter; Research; Research Personnel; Research Technics; Role; Satiation; Sensory; Signal Transduction; Somatostatin; Specific qualifier value; Stimulus; Stomach; System; Techniques; Testing; Training; Transcript; Transgenic Organisms; Vagus nerve structure; Viral; Virus; Visceral; Wireless Technology; brain pathway; comorbidity; diet-induced obesity; effective therapy; energy balance; food quality; genetic manipulation; hindbrain; insight; neural circuit; neural network; neuromechanism; new therapeutic target; novel; obese patients; obesity treatment; optogenetics; pleasure; rabies viral tracing; relating to nervous system; response; satisfaction; single-cell RNA sequencing; stem; therapeutically effective; tool; urocortin

Project Summary Obesity continues to be a major health crisis, afflicting populations worldwide with comorbidities that include type 2 diabetes and cardiovascular disease. This has stimulated research of neural circuits regulating energy balance, and technological advances have allowed for the dissection of genetically-defined brain circuits controlling feeding behavior and physiology. Studies have revealed complex central circuits, which ultimately exist for integrating endocrine and peripheral sensory signals. The vagus nerve is a critical sensory pathway for the control of meal termination and is the only direct neural link between the gut and brain. Vagal sensory afferents innervate the gastrointestinal tract and inform the brain of the quantity and quality of food being consumed. Similar to other neural systems, the vagus nerve contains heterogeneous neuronal populations that have discrete connections and perform specialized functions. However, most of what is known about the vagus and behavior comes from non-specific surgical and chemical ablation studies that do not provide mechanistic insight about distinct neuronal populations. Hence, little is known regarding primary sensory signals directly related to satiation, and research in this area is imperative for understanding the central organization and regulation of energy homeostasis. Studies in this proposal will utilize state-of-the-art wireless technology and viral/transgenic techniques to manipulate genetically defined vagal afferent neurons innervating the stomach. We will examine the relative roles of distinct gastric vagal afferent neurons in the control of food intake, which could potentially lead to the identification of novel therapeutic targets for the safe and effective treatment of obesity. 1

项目摘要 肥胖仍然是一个主要的健康危机，困扰着世界各地的人群，其合并症包括 2型糖尿病和心血管疾病。这刺激了对调节能量的神经回路的研究 平衡和技术进步已经允许解剖基因定义的大脑回路 控制进食行为和生理。研究揭示了复杂的中央回路， 是为了整合内分泌和外周感觉信号而存在的。迷走神经是重要的感觉通路 控制进食终止，是肠道和大脑之间唯一的直接神经联系。迷走神经感觉 传入神经支配胃肠道，并告知大脑食物的数量和质量。 消耗与其他神经系统类似，迷走神经包含异质神经元群体， 具有离散连接并执行专门功能。然而，大多数关于迷走神经的知识 和行为来自非特异性手术和化学消融研究， 了解不同的神经元群体。因此，对于直接的初级感觉信号知之甚少 这一领域的研究对于理解中央组织和 能量平衡的调节这项建议的研究将利用最先进的无线技术， 病毒/转基因技术来操纵遗传上确定的支配胃的迷走传入神经元。 我们将研究不同的胃迷走神经传入神经元在控制食物摄入中的相对作用， 可能导致新的治疗靶点的识别，用于安全有效的治疗 肥胖 1