Dissecting Viscerosensory Pathways Controlling Feeding Behavior

剖析控制进食行为的内脏感觉通路

基本信息

批准号：
10630205
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
项目类别：
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/10630205
关键词：
Ablation Affective Afferent Neurons Afferent Pathways Area Behavior Behavior Control Body Weight 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 Learning Link Molecular Genetics Mus Nausea Neurons Neuropeptides Non-Insulin-Dependent Diabetes Mellitus Obese Mice Obesity 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 Technology 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 manufacture neural neural circuit neural network neuromechanism new therapeutic target novel obese patients obesity treatment optogenetics rabies viral tracing response satisfaction single-cell RNA sequencing stem therapeutically effective tool transmission process urocortin wireless

项目摘要

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

项目概要肥胖仍然是一个重大的健康危机，困扰着世界各地的人们，其并发症包括： 2型糖尿病和心血管疾病。这刺激了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摄食行为和生理。研究揭示了复杂的中央回路，最终存在用于整合内分泌和外周感觉信号。迷走神经是重要的感觉通路用于控制进餐终止，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，并向大脑通报食物的数量和质量消耗了。与其他神经系统类似，迷走神经包含异质神经元群，具有离散连接并执行专门功能。然而，关于迷走神经的大部分了解行为来自非特异性手术和化学消融研究，不提供机制对不同神经元群体的洞察。因此，对直接初级感觉信号知之甚少与饱腹感有关，这一领域的研究对于理解中央组织和能量稳态的调节。该提案的研究将利用最先进的无线技术和病毒/转基因技术来操纵神经支配胃的遗传定义的迷走神经传入神经元。我们将检查不同胃迷走神经传入神经元在控制食物摄入中的相对作用，可能会导致确定新的治疗靶点，以安全有效地治疗肥胖。 1