Neural Dynamics Underlying Feeding

喂养背后的神经动力学

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要该提案调查了控制饱满的机制。这是生理学的基本问题并且与肥胖症也有相关性，因为进餐量是整体食物摄入量的重要决定因素。这孤立道（CNT）的尾核包含用于膳食终止的关键神经回路。这些电路整合来自神经腹部内脏的迷走神经传入以及循环激素和营养信号是为了触发进食的终止。虽然长期研究了CNTS细胞类型使用各种方法，其行为过程中的自然活动模式几乎完全未知。解决此知识差距将揭示调节CNT神经元的关键信号的性质正常喂养，这些信号如何集成到特定的单元格中，以及它们在课程中的发展方式一顿饭。在初步研究中，我们开发了记录CNTS神经元活性的方法在进食过程中表征小鼠并表征其动力学，并响应各种内脏刺激。在这里，我们建议以这些发现为基础，以系统地剖析调节CNT饱腹感的信号体内电路。在目标1和2中，我们在GI区的各个阶段操纵输入，并测量如何改变进食过程中CNT的动力。在AIM 3中，我们使用靶向的光遗传操作来增强或阻止这些神经元的自然活动模式的元素，并测量这种神经元的摄入和进餐如何改变食物的摄入量微观结构。这些实验将共同揭示尾脑干如何动态整合各种输入以逐步控制进食行为。