Dissecting Viscerosensory Pathways Controlling Feeding Behavior

剖析控制进食行为的内脏感觉通路

• 批准号: 10406287
• 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/10406287
• 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; wireless

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

项目总结