Neural Dynamics Underlying Feeding

喂养背后的神经动力学

• 批准号: 10454079
• 负责人: Zachary A. Knight
• 金额: $ 50.98万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-20 至 2027-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10454079
• 关键词: Abdomen; Address; Animals; Behavior; Bite; Blood; Body Weight; Brain; Brain Stem; Brain region; Calcium; Chemicals; Cholecystokinin; Consumption; Cues; Dependence; Diet; Eating; Elements; Feedback; Feeding behaviors; Food; Gastrointestinal tract structure; Hormonal; Hormones; Infusion procedures; Ingestion; Intestines; Knowledge; Learning; Liquid substance; Measures; Methods; Mus; Nature; Neurons; Neurosciences; Nucleus solitarius; Nutrient; Obesity; Operative Surgical Procedures; Optics; Oral; Pattern; Pharmacology; Phase; Physiology; Process; Prosencephalon; Rattus; Regulation; Reporting; Satiation; Signal Transduction; Stimulus; Stomach; Stretching; System; Taste Perception; Testing; Time; Viscera; Visceral; awake; blind; cell type; conditioning; experimental study; feeding; food consumption; gastrointestinal; in vivo; mechanical signal; neural circuit; noradrenergic; optogenetics; relating to nervous system; response; sham feeding

Project Summary This proposal investigates the mechanisms that control satiation. This is a fundamental problem in physiology and also has relevance to obesity, because meal size is an important determinant of overall food intake. The caudal nucleus of the solitary tract (cNTS) contains key neural circuits for meal termination. These circuits integrate input from vagal afferents innervating the abdominal viscera as well as circulating hormonal and nutrient signals in order to trigger the termination of feeding. While cNTS cell types have long been studied using a variety of approaches, their natural activity patterns during behavior are almost completely unknown. Addressing this knowledge gap would reveal the nature of the key signals that regulate cNTS neurons during normal feeding, how these signals are integrated in specific cell types, and how they evolve during the course of a meal. In preliminary studies, we developed methods to record the activity of cNTS neurons in freely behaving mice and characterized their dynamics during feeding and in response to a variety of visceral stimuli. Here we propose to build on these findings to systematically dissect the signals that regulate cNTS satiety circuits in vivo. In Aims 1 and 2, we manipulate inputs at various stages of the GI tract and measure how this alters cNTS dynamics during feeding. In Aim 3, we use targeted optogenetic manipulations to boost or block elements of the natural activity patterns of these neurons and measure how this alters food intake and meal microstructure. Together, these experiments will reveal how the caudal brainstem dynamically integrates diverse inputs to enable the moment-by-moment control of feeding behavior.

项目概要 该提案研究了控制饱腹感的机制。这是生理学的一个基本问题 也与肥胖有关，因为膳食量是总体食物摄入量的重要决定因素。这 孤束尾核（cNTS）包含进餐终止的关键神经回路。这些电路 整合来自支配腹部内脏的迷走神经传入以及循环激素和 营养信号以触发喂养终止。虽然 cNTS 细胞类型早已被研究 使用各种方法，他们行为过程中的自然活动模式几乎完全未知。 解决这一知识差距将揭示调节 cNTS 神经元的关键信号的本质 正常喂养，这些信号如何整合到特定细胞类型中，以及它们在过程中如何进化 一顿饭。在初步研究中，我们开发了自由记录 cNTS 神经元活动的方法 研究小鼠的行为并表征它们在进食期间以及对各种内脏刺激的反应过程中的动态。 在这里，我们建议以这些发现为基础，系统地剖析调节 cNTS 饱腹感的信号 体内电路。在目标 1 和 2 中，我们操纵胃肠道各个阶段的输入并测量其如何 在进食过程中改变 cNTS 动力学。在目标 3 中，我们使用有针对性的光遗传学操作来增强或阻止 这些神经元自然活动模式的要素，并测量这如何改变食物摄入和膳食 微观结构。这些实验将共同揭示尾部脑干如何动态整合 多样化的输入能够实时控制进食行为。