Diverse control of motivational and consummatory feeding by a hindbrain dopaminergic neural circuit

后脑多巴胺能神经回路对动机和完成性喂养的多样化控制

• 批准号: 10530670
• 负责人: Qi Wu
• 金额: $ 35.95万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530670
• 关键词: Affect; Anabolism; Appetitive Behavior; Behavior; Behavioral; Behavioral Paradigm; Biological Assay; Body Weight; Brain Stem; Brain region; CRISPR/Cas technology; Calories; Cognitive; Consumption; Coupling; DRD1 gene; Data; Desire for food; Dopamine; Eating; Electrophysiology (science); Elements; Exhibits; Feeding behaviors; Food; Gene Targeting; Genes; Genetic; Genetic Suppression; High Fat Diet; Hyperphagia; Individual; Learning; Maps; Mediating; Mediation; Modeling; Motivation; Neurons; Nucleus Accumbens; Nutritional; Obesity; Outcome; Pattern; Physiological; Play; Population; Process; Psychological reinforcement; Regulation; Rewards; Role; Satiation; Satiety Response; Signal Transduction; Solid; Stereotyping; Stimulus; Substantia nigra structure; System; Taste Perception; Techniques; Testing; Time; Ventral Tegmental Area; Viral; Virus; Weight maintenance regimen; cell type; cohort; dopaminergic neuron; feeding; gain of function; gamma-Aminobutyric Acid; hindbrain; in vivo; innovation; interdisciplinary approach; loss of function; mesolimbic system; mind control; neural circuit; neuromechanism; new therapeutic target; novel; obesity treatment; optogenetics; parabrachial nucleus; permissiveness; postsynaptic; preference; response; targeted treatment; tool

Project Summary: The mesolimbic dopamine (DA) system is composed of DA neurons in the ventral tegmental area (VTA) and substantia nigra compacta (SNc). It is well studied that DA neurons project to the nucleus accumbens (NAc) in mediation of reinforcement learning and reward. But the physiological role of dopamine in specific control of appetite and the underlying neural circuit remain elusive. To assess input-specific effects of motivational feeding behaviors, we employ a multidisciplinary approach combining in vivo optogenetics, in vivo electrophysiology, viral-based circuit tracing, and various behavioral paradigms. We identify a novel VTA-PBN neural circuit that plays a pivotal role in control of appetitive and consummatory feeding. Here we suggest a novel neural mechanism by which a subset of PBN-projecting DA and GABA neurons controls feeding and body weight. We further identify a group of PBN neurons as the post-synaptic targets of the VTA neurons that uniquely contribute to feeding and food-conditioned behavior. This project advances a novel concept that a genetically distinguishable VTA-PBN neural circuit selectively and differentially mediates appetitive response and consummatory feeding under distinct nutritional and cognitive states.

项目概述：中脑边缘多巴胺（DA）系统由腹侧的DA神经元组成 被盖区（VTA）和黑质腹侧区（SNc）。DA能神经元投射到神经元之间的关系已经得到很好的研究， 在强化学习和奖励的中介作用中，神经核（NAc）。但 多巴胺在特定食欲控制中的生理作用和潜在的神经回路仍然存在 难以捉摸。为了评估动机性喂养行为的特定输入效应，我们采用了 结合体内光遗传学、体内电生理学、基于病毒的 电路跟踪和各种行为范例。我们确定了一种新的VTA-PBN神经回路， 在控制食欲和进食方面起着关键作用。在这里我们建议一本小说 一种神经机制，通过这种机制，PBN投射DA和GABA神经元的子集控制进食， 体重我们进一步确定了一组PBN神经元作为VTA的突触后靶点 这些神经元对进食和食物调节行为有独特的贡献。该项目推进了A 一种新的概念，即选择性和差异性地遗传可区分的VTA-PBN神经回路 在不同的营养和认知条件下， states.