A novel lateral hypothalamic neurocircuit enhances rewarding aspects of feeding

一种新型的下丘脑外侧神经回路增强了进食的奖励性

• 批准号: 9756766
• 负责人: Ryan M Cassidy
• 金额: $ 3.25万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9756766
• 关键词: Affect; Alcohol consumption; Alcohols; Anxiety; Appetitive Behavior; Automobile Driving; Behavior; Behavioral; Brain; Brain region; Calories; Candy; Cell Nucleus; Consumption; Cues; Data; Decision Making; Developed Countries; Development; Diagonal Band of Broca; Eating; Electrophysiology (science); Equilibrium; Esthesia; Evaluation; Fasting; Feeding behaviors; Fiber Optics; Food; Food deprivation (experimental); Future; Hunger; Hypothalamic structure; Immunohistochemistry; Individual; Laboratories; Lasers; Lateral; Medial; Mediating; Mediator of activation protein; Metabolic; Metabolic Diseases; Midbrain structure; Modernization; Molecular; Motivation; Mus; Neurobiology; Neurons; Neurosciences; Neurosecretory Systems; Nicotine; Obesity; Obesity Epidemic; Opioid; Palate; Pathogenesis; Peripheral; Phenotype; Physicians; Physiological; Population; Property; Psychiatrist; Relapse; Reporting; Research; Rewards; Role; Satiation; Scientist; Self Stimulation; Signal Transduction; Somatostatin; Substance abuse problem; Substance of Abuse; Synapses; System; Techniques; Testing; Time; Tracer; Training; United States; Veins; addiction; basal forebrain; behavior test; cholinergic; cholinergic neuron; craving; energy balance; experience; fast food; feeding; food consumption; gamma-Aminobutyric Acid; ghrelin; hormonal signals; in vivo calcium imaging; innovation; insight; interest; intravenous administration; motivated behavior; neurotransmission; novel; novel therapeutics; obesity treatment; optogenetics; postsynaptic neurons; preference; presynaptic neurons; relating to nervous system; reward circuitry; soft drink; systems research

Project Summary/Abstract The percentage of the population afflicted by obesity has relentlessly increased over the past century in industrialized countries. This has closely tracked the development of widely available, calorically dense, highly palatable foods (fast food, candy, soda, etc). Overconsumption is a necessary component in the pathogenesis of obesity. However, the mechanisms by which the homeostatic neurocircuits regulating the balance between sensations of hunger and satiety are disrupted is not yet known. Interestingly, there is mounting evidence that the neural and hormonal signals indicating negative energy balance (e.g. ghrelin) directly increase the sensitivity of the motivational neurocircuitry. It appears that hunger may represent a state of reward sensitivity; thus, food consumption may primarily rely upon the evaluated rewarding properties of the food in question. Understanding the brain phenomena which make food seem so rewarding will allow the development of novel therapies and more targeted approaches in treatment of obesity. The lateral hypothalamus is a key mediator of cue- and reward-mediated feeding behavior and understanding its function in both reward and food acquisition will lend this insight. In this proposal, we aim to characterize, for the first time, the behavioral consequence of activating the lateral hypothalamus (LH) projections to basal forebrain nuclei (medial septum and diagonal band of broca M/D). We have identified a unique combination of both induced food consumption - indicating hunger - and preference for self-stimulation over food consumption despite being in a food deprived state -indicating it is intrinsically rewarding. Thus, we propose to elaborate and characterize on this unique phenotype. We also propose to identify the molecular identity of both the pre- and postsynaptic neurons in this circuit, with the hypothesis that lateral hypothalamic GABAergic neurons synapse on dual GABAergic and cholinergic neurons in the basal forebrain. This comprehensive study of the function of the LHM/D circuit will be the first to report on this projection and lend further mechanistic insight into the crosstalk between hunger and reward. It will also provide the PI with substantial training and experience to become a productive and innovative psychiatrist and physician scientist in the future.

项目摘要/摘要 在过去的一个世纪中，肥胖折磨的人口百分比在 工业化国家。 可口的食物（快餐，糖果，苏打等）是发病机理的必要组成部分 肥胖。 尚不清楚饥饿和卫星的感觉。 神经和荷尔蒙信号表明负能量平衡（例如，生长素素）直接提高灵敏度 在激励性神经循环中，饥饿似乎代表了奖励敏感性 消费可能主要依赖于所评估的食物的奖励。 使食物看起来如此的大脑现象将允许开发新的疗法和 肥胖治疗方面的更多针对性方法。 奖励介导的喂养行为，并了解其在奖励和食物食品食品获取方面的功能 这个洞察力。 下丘脑（LH）的侧向前脑核（Broca的内侧和对角线带 m/d）。 偏爱自我刺激而不是食物消费，尽管处于贫困状态 - 从本质上讲，我们提出了对这种独特的表型的精心态度。 建议识别该电路中突触后神经元的分子身份 假设下侧刺GABA能神经元在双重GABA能和胆碱能神经元上突触 在基础前脑中。 关于投影并进一步向饥饿与奖励之间的斗篷提供进一步的机械。 为PI提供大量培训和经验，以成为一名富有成效和创新的精神科医生，并且 将来的医师科学家。