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Neural circuit control of mesolimbic dopamine and reward

中脑边缘多巴胺和奖励的神经回路控制

基本信息

批准号：
10175425
负责人：
Daniel Patrick Covey
金额：
$ 24.9万
依托单位：
LOVELACE BIOMEDICAL & ENVIRONMENTAL RESEARCH INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10175425
关键词：
Adaptive Behaviors Amphetamines Behavior Behavioral Brain Brain region CNR1 gene Calcium Cells Consumption Cues Desire for food Disease Dopamine Drug Addiction Drug abuse Electron Microscopy Elements Fiber Food Functional disorder Glutamates Goals Hyperphagia Hypothalamic structure Image Immunohistochemistry In Situ Hybridization Individual Institution Intake Lateral Learning Measures Mediating Mental Depression Mentors Morale Motivation National Institute of Drug Abuse Neurons Nucleus Accumbens Obesity Optics Pathway interactions Pattern Pharmaceutical Preparations Phase Photometry Population Presynaptic Terminals Process Psychopathology Research Research Proposals Rewards Role Self Administration Shapes Signal Transduction Sucrose Synapses Techniques Training Ventral Tegmental Area Viral Work cell type cellular targeting clinically relevant dopaminergic neuron drug of abuse drug reinforcement drug reward effective therapy endocannabinoid signaling endogenous cannabinoid system experience experimental study gamma-Aminobutyric Acid genetic approach health economics knock-down motivated behavior neural circuit neuromechanism novel optogenetics psychostimulant relating to nervous system response reward processing skills therapy development virtual virus genetics

项目摘要

Project Summary Mesolimbic dopamine (DA) projections from the ventral tegmental area (VTA) to nucleus accumbens (NAc) serve a fundamental role in goal-seeking. This neural circuit is thus central to adaptive behavior (e.g., finding food), but can also promote psychopathologies characterized by hyper-motivation (e.g., drug abuse or obesity) or hypo- motivation (e.g., apathy or depression), all of which exact an enormous toll on individual an economic health. Afferent projections from numerous brain regions synapse onto VTA DA neurons to control their activity. The current proposal aims to identify how specific inputs to DA neurons contribute to their role in motivated behaviors and disease states. This work will focus on two primary mechanisms controlling brain DA function and reward- related behavior. First, the lateral hypothalamus (LH) has been the subject of intense research for well over 50 years due to its fundamental role in virtually all aspects of motivated behaviors, reward processing, and reward consumption. Second, the endocannabinoid (eCB) system is a vast signaling network that acts throughout the brain and periphery to regulate numerous homoeostatic processes, but serves a particularly important role in modulating brain DA function. We will use state-of-the art techniques to identify cell type- and neural circuit- specific mechanisms by which eCB signaling controls LH influence on DA neurons and how these mechanisms contribute to specific components of food-seeking behaviors. We will then assess similarities and differences between the neuronal mechanisms that control food seeking versus drug-seeking by investigating their role in the voluntary intake of amphetamine, one of the most widely abused drugs worldwide. Together, these experiments aim to elucidate the functional overlap and distinctions between precise neural circuit mechanisms that control adaptive versus aberrant forms of reward-driven behavior, with the ultimate goal of fundamentally understanding motivated actions and developing safe and effective treatments for aberrant forms of reward seeking that characterize, for example, drug abuse or obesity.

项目总结