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Genetically Dissecting Chorinergic Signaling in Body Weight Control

从基因角度剖析体重控制中的胆碱能信号

基本信息

批准号：
10647885
负责人：
Benjamin R Arenkiel
金额：
$ 45.54万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-07-15 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10647885
关键词：
Acute Address Affect Anatomy Area Attention Award Behavior Behavioral Body Weight Brain Brain region Cardiovascular Diseases Cause of Death Central Nervous System Chronic Communication Data Desire for food Diabetes Mellitus Diagonal Band of Broca Diet Diet Habits Eating Eating Behavior Electrophysiology (science)Fasting Feeding behaviors Food Food Aversion Genetic Glutamates Goals Habenula Healthy Eating Homeostasis Hyperphagia Hypothalamic structure Knowledge Lateral Life Link Mediating Mental Depression Metabolic Metabolism Nature Neurons Obesity Obesity associated disease Population Prosencephalon Research Proposals Research Support Rewards Role Satiation Sensory Signal Pathway Signal Transduction Starvation Synapses Testing United States Wakefulness Weight maintenance regimen With laterality addiction basal forebrain basal forebrain cholinergic neurons cell type cholinergic cholinergic neuron energy balance experimental study feeding food consumption glutamatergic signaling insight neural neuronal circuitry neurotransmission novel nutrient metabolism obesity development optogenetics programs reward processing

项目摘要

Abstract/Project Summary Obesity-associated diseases such as diabetes and cardiovascular disease together account for the leading cause of death in the United States. Roughly one-third of the U.S. population is obese, and it is estimated that nearly half of the population will be obese within the next two decades. To date, studies investigating the neural contribution to body weight control have focused largely on neuropeptidergic signaling in the hypothalamus, a key brain region involved in feeding behavior. However, signaling from extra-hypothalamic brain regions has also been implicated in regulating nutrient metabolism, appetite, and satiety. We have recently uncovered a novel mechanism by which glutamatergic signaling in the basal forebrain strongly influences feeding and body weight control. This discovery provides intriguing evidence that specific glutamatergic signaling pathways in the brain critically regulate feeding behavior and body weight homeostasis. To elucidate the mechanisms by which forebrain glutamatergic signaling influences body weight management, feeding behaviors, and metabolism, we will test the hypothesis that glutamatergic basal forebrain circuits modulate metabolic and appetitive programs to regulate body weight. Using a combination conditional genetic targeting, optogenetic manipulations, electrophysiology, and behavioral analysis, we will set out to determine the role for basal forebrain glutamatergic signaling in body weight control and obesity.

摘要/项目摘要与肥胖相关的疾病，如糖尿病和心血管疾病，美国的死因。大约有三分之一的美国人口肥胖，据估计，近一半的人口将在未来二十年内肥胖。迄今为止，研究神经系统的研究对体重控制的贡献主要集中在下丘脑中的神经肽能信号，与进食行为有关的关键脑区然而，来自下丘脑外脑区的信号还涉及调节营养代谢、食欲和饱腹感。我们最近发现了一个一种新的机制，通过这种机制，基底前脑中的多巴胺能信号强烈影响摄食和身体体重控制这一发现提供了有趣的证据，表明在大脑中的特定的多巴胺能信号通路，大脑严格地调节进食行为和体重动态平衡。为了阐明前脑神经元能信号影响体重管理、摄食行为和代谢，我们将检验这一假设，即多巴胺能基底前脑回路调节代谢和食欲程序来调节体重使用条件遗传靶向、光遗传学操作、电生理学和行为分析，我们将着手确定基底前脑多巴胺能神经元的作用，在体重控制和肥胖症中的信号传导。