Neural basis of incentive and expected value representations

激励和期望值表示的神经基础

• 批准号: 10578757
• 负责人: Jocelyn M Richard
• 金额: $ 34.88万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10578757
• 关键词: Abstinence; Affect; Behavior; Behavior Control; Behavioral Mechanisms; Brain; Calcium Signaling; Complex; Conditioned Stimulus; Cues; Decision Making; Drug Addiction; Drug usage; Electrophysiology (science); Emotional; Fiber; Fluorescence; Future; Globus Pallidus; Goals; Healthcare; Incentives; Individual; Knowledge; Measures; Modeling; Motivation; Motor output; Neurons; Nucleus Accumbens; Outcome; Output; Pathway interactions; Pattern; Pharmaceutical Preparations; Photometry; Population; Positive Reinforcements; Predictive Value; Property; Public Health; Punishment; Rattus; Relapse; Research; Rewards; Role; Signal Transduction; Stimulus; Structure; Testing; Thalamic structure; Time; Ventral Tegmental Area; Virus; Work; addiction; adverse outcome; alcohol seeking behavior; basal forebrain; behavioral response; brain based; calcium indicator; cocaine seeking; cost; gamma-Aminobutyric Acid; in vivo; mental representation; motivated behavior; neural; neural circuit; neural model; neuromechanism; neuropsychiatric disorder; neuroregulation; neurotransmission; optogenetics; outcome prediction; targeted treatment

Project Summary The incentive value of drug-associated cues drives several facets of addiction, including escalation of drug use and the propensity to relapse even after long periods of abstinence. Cues with high incentive value can drive reward-seeking behaviors that are disconnected from an individual’s goals and the value of expected outcomes (i.e. rewards or punishments). This may lead to perseverative or compulsive drug use despite adverse consequences. A critical barrier to progress in neuromodulation-based treatments for addiction is lack of knowledge regarding the circuits engaged in cue-driven reward-seeking behavior, and how these circuits are distinct from those involved in goal-directed behavior, which relies on accurate mental representations of expected outcomes and their value. This proposal focuses on the role of the ventral pallidum (VP), a region of the basal forebrain that is critical for both relapse to drug use and positive affect. Our objective is to identify the VP neural populations that encode the incentive value of cues, and the neural circuit mechanisms by which cues drive motivated behavior. Our central hypothesis is that neurons that represent the incentive value of cues are distinct from those that represent the expected value of future outcomes, and that these neurons can be defined based on output pathway. We predict that the activity of GABAergic VP neurons projecting to the ventral tegmental area (VTA) encodes cue-driven reward-seeking and that activity in this population is critical for cue-driven motivated behavior. We will test our hypothesis by pursuing the following aims. In Aim 1 we will examine encoding of the incentive value of cues and expected value of outcomes by individual neurons in VP. Our hypothesis is that separate neurons in VP encode incentive value and expected value. We will use in vivo single unit electrophysiology to measure activity patterns in individual VP neurons during presentations of reward-related cues and determine whether activity in these neurons predicts cue- elicited reward-seeking behavior and/or the current expected value of a predicted outcome. In Aim 2 we will identify the VP output pathway(s) that encode the incentive value of cues. Our hypothesis is that VP neurons that encode incentive value are GABAergic and project to the VTA. We will use fiber photometry to measure calcium signals in VP GABA neurons projecting to the VTA or thalamus during presentations of reward cues and determine whether activity in these populations predicts cue-elicited reward-seeking behavior and/or expected value. In Aim 3 we will test the functional role of activity in these VP output pathways in behavioral responses to cues. Successful completion of this research will characterize the brain mechanisms of incentive value representations and define the downstream circuit targets for the invigoration of motivated behavior by VP incentive value signals. Advancements in our understanding of these circuits will contribute to the refinement of brain-based therapies that target the neural mechanisms underlying compulsive drug use.

项目摘要 与药物相关的提示的激励价值驱动驱动驱动的截止方面，包括升级 使用毒品和戒酒的复发倾向。 可以推动寻求奖励行为的行为，这些行为与个人的目标和预期的价值脱节 结果（即奖励或惩罚）。 不利后果。 关于从事提示驱动的奖励行为以及这些电路的知识 不同于参与目标指导行为的行为，这依赖于准确的心理代表 预期的结果及其价值。 对药物使用和积极影响既批判性的基础前脑都是批判性的。 VP神经受欢迎程度，提示的激励价值以及Whwich的神经回路机制 提示动机行为。我们的中心假设是 提示与代表预期结果的预期值不同，这些神经元可以 根据输出途径定义。 腹侧对段区域（VTA）编码提示驱动的寻求奖励和该活动中的活动 对于提示驱动的动机行为，我们将通过追求以下目标来检验假设。 在AIM 1中，我们将检查提示的激励价值和结果的预期价值的编码 我们的假设中的个体神经元。 价值。 在与奖励相关线索的介绍中，并确定这些神经元中的活性是否预测提示 - 引起奖励性行为和/或当前的期望值 确定编码线索激励值的VP输出途径。 该编码激励值是GABA能和VTA的项目。 奖励提示期间投射到VTA或Thalamus的VP GABA神经元中的钙信号 并确定这些Poptions中的活动是否预测提示引用的寻求奖励行为和/或 AIM 3中的预期值我们将在这些VP输出途径中测试功能角色 对线索的响应。 值代表并定义下游电路目标，以通过 VP的激励价值信号。 基于大脑的疗法的细化针对强迫药物使用的神经机制。