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：
10681782
负责人：
Daniel Patrick Covey
金额：
$ 24.57万
依托单位：
LOVELACE BIOMEDICAL 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/10681782
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.

项目摘要从腹侧对盖面积（VTA）到伏隔核（NAC）服务的中唇多巴胺（DA）投影在寻求目标中的基本作用。因此还可以促进以过度动机（例如药物滥用或肥胖）或低功率为特征的心理病理学动机（例如冷漠或抑郁症），所有这些都给个人带来了巨大的经济健康损失。来自众多大脑区域的传入投影突触到VTA DA神经元中，以控制其活性。这当前的建议旨在确定对DA神经元的特定输入如何促进其在动机行为中的作用和疾病状态。这项工作将着重于控制大脑DA功能和奖励的两种主要机制 - 相关行为。首先，下丘脑（LH）已成为超过50多个研究的深入研究的主题多年由于其在动机行为的几乎所有方面，奖励加工和奖励的基本作用，消耗。其次，内源性大麻素（ECB）系统是一个庞大的信号网络，在整个过程中起作用大脑和外围调节众多均静态过程，但在调节大脑DA功能。我们将使用最先进的技术来识别细胞类型和神经回路 - 欧洲央行信号传导控制LH对DA神经元的影响以及这些机制的特定机制有助于寻求食物行为的特定组成部分。然后，我们将评估相似性和差异通过调查其在控制食物与寻求药物的神经元机制之间，通过研究其在苯丙胺的自愿摄入量是全球最广泛滥用的药物之一。在一起，这些实验旨在阐明功能重叠和精确神经回路机制之间的区分控制自适应与异常形式的奖励驱动行为，最终的目标是了解动机行动并为异常奖励形式开发安全有效的治疗寻求这种特征，例如吸毒或肥胖。

项目成果

期刊论文数量（2）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Potential Involvement of a Substantia Nigra Circuit in Opioid Reinforcement.

黑质回路在阿片类药物强化中的潜在参与。

DOI：
10.1523/jneurosci.3220-20.2021
发表时间：
2021
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
0
作者：
Oliver,RobertJ
通讯作者：
Oliver,RobertJ

Evolution of in vivo dopamine monitoring techniques.

体内多巴胺监测技术的演变。