Dissecting Viscerosensory Pathways Controlling Feeding Behavior

项目摘要 肥胖症仍然是一个主要的健康危机，困扰着世界各地的人口，他们的共病包括 2型糖尿病和心血管疾病。这刺激了神经回路调节能量的研究。 平衡，以及技术进步使基因定义的大脑回路的解剖成为可能 控制摄食行为和生理。研究揭示了复杂的中央回路，最终 存在整合内分泌和外周感觉信号的方法。迷走神经是一条重要的感觉通路。 用于控制终止进餐，是肠道和大脑之间唯一直接的神经联系。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。 消耗掉了。与其他神经系统相似，迷走神经包含不同种类的神经元群 有独立的联系，并履行专门的职能。然而，大多数人对迷走神经的了解 而行为来自非特定的外科和化学消融研究，这些研究没有提供机械性的 对不同神经元群体的洞察。因此，对初级感觉信号的直接了解甚少。 与饱足有关，这方面的研究对于理解中央组织和 调节能量动态平衡。这项计划中的研究将利用最先进的无线技术和 病毒/转基因技术操纵支配胃的基因定义的迷走神经传入神经元。 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量中的相对作用， 可能导致确定新的治疗靶点，用于安全和有效地治疗 肥胖。 1

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