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

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要：中唇多巴胺（DA）系统由腹侧的DA神经元组成支盖面积（VTA）和黑质Nigra Compacta（SNC）。已经很好地研究了DA Neurons项目在加强学习和奖励的调解中，伏隔核（NAC）。但是多巴胺在食欲的特定控制和潜在的神经回路中的生理作用仍然存在难以捉摸。为了评估动机喂养行为的投入特异性影响，我们采用了多学科方法结合体内光遗传学，体内电生理学，基于病毒电路跟踪和各种行为范式。我们确定了一种新颖的VTA-PBN神经电路在控制食用和完整喂养方面起关键作用。在这里，我们建议一本小说神经机制，通过PBN进行DA和GABA神经元的子集控制进食和体重。我们进一步将一组PBN神经元视为VTA的突触后靶标独特的神经元有助于进食和食物条件的行为。这个项目推进了新颖的概念是一种可选择性和差异性的遗传学区分VTA-PBN神经回路在不同的营养和认知下介导食欲的反应和完整的喂养国家。