Brain Circuit Mechanisms for Reward Cue Attraction

奖励提示吸引的脑回路机制

• 批准号: 10223253
• 负责人: Kyle S Smith
• 金额: $ 48.14万
• 依托单位: DARTMOUTH COLLEGE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-30 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10223253
• 关键词: Acetylcholine; Addictive Behavior; Address; Animals; Area; Attention; Behavior; Biological Assay; Brain; Cells; Clozapine; Complement; Consumption; Contralateral; Cues; Desire for food; Drug Addiction; Drug usage; Eating Behavior; Equilibrium; Food; Gene Expression Profiling; Globus Pallidus; Goals; Immediate-Early Genes; Lateral; Lead; Ligands; Maps; Measures; Medial; Methods; Modeling; Motivation; Neurons; Nucleus Accumbens; Outcome; Oxides; Pathologic; Pathway interactions; Pattern; Pharmaceutical Preparations; Physiological; Population; Procedures; Process; Rattus; Reaction; Research; Rewards; Role; Saline; Stimulus; Symptoms; Technology; Testing; Transgenic Organisms; Viral; Work; addiction; base; cholinergic; cholinergic neuron; designer receptors exclusively activated by designer drugs; expectation; experimental study; feeding; incentive salience; motivated behavior; motivational processes; neural circuit; neural model; receptor; recruit; reduced food intake; relating to nervous system; remote control

Drug addiction involves an excessive motivation to pursue and consume drugs. Part of this motivation is thought to involve the attribution of value to drug-paired cues. Cues for rewards, including drugs and food, can become motivational targets and attract attention and behavior. In the brain, a basic sketch of areas responsible for this process is known and includes the nucleus accumbens (NAc) and ventral pallidum (VP). Although these areas are bidirectionally connected as a circuit, little is known about how motivation arises out of their circuit dynamics. To address this, the proposed research will incorporate a method called chemogenetics for relatively non-invasive “remote control” perturbation of brain activity. Combining this method with transgenic delivery strategies, we will both increase and decrease activity in pathways connecting the NAc and VP to evaluate their role in the motivational attraction to reward cues. This motivational process is exemplified by sign-tracking behavior, in which animals appetitively engage with a cue predicting reward. In the proposed research, connections between the NAc and VP will be manipulated using DREADDs to assess the role of these pathways in acquiring and expressing the sign-tracking behavior. Recordings of neural activity and gene expression assays will complement these experiments in order to establish neural activation patterns that change in register with changes in motivated behavior. We will similarly test the role of neurons in the VP expressing acetylcholine, which receive NAc input and are hypothesized to guide attention towards reward cues. Results showing how NA-VP circuits control motivation, and what neural activity signatures map on to increases and decreases in motivation, will provide critical reference points for an understanding of how pathway-specific changes in brain activity could contribute to excessive motivation in addictive behaviors. The relative non-invasiveness of the procedure also carries translational potential for disrupting severely excessive reactions to drug-associated stimuli.

吸毒成瘾涉及追求和食用药物的过多动力。一部分 人们认为，这种动机涉及价值对药物培养提示的属性。提示 包括毒品和食物在内的奖励可以成为动机目标和吸引力的关注，并且 行为。在大脑中，已知负责此过程的区域的基本草图，并且 包括伏隔核（NAC）和腹侧颗粒（VP）。尽管这些区域是 双向连接作为电路，对动机的发展知之甚少 电路动力学。为了解决这个问题，拟议的研究将结合一种称为的方法 相对非侵入性的“遥控”脑活动的化学遗传学。 将此方法与转基因交付策略相结合，我们将增加和减少 连接NAC和VP的路径中的活动，以评估它们在激励性中的作用 吸引奖励提示。 这一动机的过程是通过签名跟踪行为来体现的，其中动物 与预测奖励的提示互动。在拟议的研究中，连接 在NAC和VP之间将使用Dreadds操纵NAC和VP，以评估这些作用 获取和表达签名行为的途径。神经活动的记录 基因表达测定将完成这些实验以建立神经 激活模式随着动机行为的变化而变化的注册模式。我们会同样 测试神经元在表达乙酰胆碱的VP中的作用，该乙酰胆碱接收NAC输入并且是 假设是为了指导注意力提示。结果显示了NA-VP电路 控制动机以及哪些神经活动签名映射以增加和减少 动机，将提供关键参考点，以了解如何特定道路 大脑活动的变化可能导致累加行为的过多动机。这 该过程的相对非侵入性也具有破坏的翻译潜力 对与药物相关的刺激的反应严重过度。