Mesostriatal dopamine in Pavlovian reward rate learning

巴甫洛夫奖赏率学习中的中纹状体多巴胺

• 批准号: 10464750
• 负责人: Eric Garr
• 金额: $ 7.23万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10464750
• 关键词: Attention; Auditory; Axon; Behavior; Behavior Control; Belief; Cells; Cues; Dependence; Dopamine; Environment; Event; Fiber; Future; Genetic Recombination; Goals; Human; Image; Investigation; Learning; Machine Learning; Measures; Mediating; Methods; Midbrain structure; Modeling; Movement; N-Methyl-D-Aspartate Receptors; Neurons; Neurosciences; Nucleus Accumbens; Opsin; Phase; Photometry; Physiological; Population; Presynaptic Terminals; Protocols documentation; Psychological reinforcement; Rattus; Receptor Activation; Relapse; Reporting; Research; Rewards; Rodent Model; Role; Signal Transduction; Spottings; Sum; Synapses; Synaptic plasticity; Time; Ventral Striatum; Ventral Tegmental Area; addiction; base; classical conditioning; cohort; conditioning; dopaminergic neuron; drug addiction therapy; drug craving; drug of abuse; experience; experimental study; insight; mutual learning; neurotransmitter release; novel therapeutics; optogenetics; postsynaptic; relating to nervous system; response; theories

PROJECT SUMMARY Dopamine (DA) signaling in the ventral striatum has received considerable attention for its role in relapse and drug craving, both in rodent models of addiction and in humans. A popular belief is that dopamine neurons in the ventral tegmental area (VTA) communicate a prediction error to the nucleus accumbens core (NAcc), where the error reports the difference between observed and expected values of cues and rewards. A critical assumption is that prediction errors are based on values, and this idea has been used to explain how drugs of abuse exert their reinforcing effects by hijacking DA-mediated value learning. However, in most studies that measure DA cell activity and neurotransmitter release, value is confounded with another variable critical for learning: mutual information, or the degree to which cues in the environment signal relative changes in reward rate. Therefore, the overall goal of this project is to investigate the extent to which an information-theoretic account of learning can be captured by mesostriatal DA dynamics. Behavioral manipulations will utilize established methods of inducing changes in mutual information between cues and rewards independent of value during Pavlovian conditioning in rats. Experiments proposed in Aim 1 will use fiber photometry to assess whether bulk activity in VTA DA neurons and DA release in the NAcc encode prediction errors based on mutual information, and whether cue-evoked responses in NAcc neurons scales with mutual information. Aim 2 will determine whether conditioned behavior will diminish when degrading mutual information between cues and optogenetic DA stimulation in either VTA cell bodies or VTA axon terminals in the NAcc. Experiments in Aim 3 will assess whether optogenetically inhibiting VTA DA neurons that project to the NAcc during moments of Pavlovian information loss will rescue conditioned behavior from dissipating, and whether stimulating cue- sensitive ensembles of NAcc neurons at the onset of information-degraded cues will also have the same effect.

项目摘要 腹侧纹状体中的多巴胺（DA）信号因其在复发和再发中的作用而受到相当大的关注。 在啮齿动物成瘾模型和人类中，一个普遍的观点是， 腹侧被盖区（VTA）将预测错误传达给丘脑核核心（NAcc）， 其中误差报告了线索和奖励的观察值与期望值之间的差异。一个关键 假设预测误差是基于值的，这个想法已经被用来解释药物是如何产生的。 虐待通过劫持DA介导的价值学习发挥其强化效应。然而，在大多数研究中， 测量DA细胞活性和神经递质释放，值与另一个关键变量混淆， 学习：相互信息，或者环境中的线索表明奖励相对变化的程度 率因此，本项目的总体目标是调查信息理论在多大程度上 学习的解释可以通过中纹状体DA动力学来捕获。行为操纵将利用 建立了诱导线索和奖励之间的互信息变化的方法， 在大鼠巴甫洛夫条件反射过程中的价值。目标1中提出的实验将使用光纤光度法来评估 VTA DA神经元中的大量活动和NAcc中的DA释放是否编码预测误差， 互信息，以及NAcc神经元中的线索诱发反应是否与互信息成比例。目的2 将决定当线索之间的互信息降低时， 以及在NAcc中的VTA细胞体或VTA轴突末梢中的光遗传学DA刺激。实验 目的3将评估是否光遗传学地抑制VTA DA神经元，其在瞬间投射到NAcc。 巴甫洛夫式信息丢失是否能挽救条件反射行为免于消散，以及刺激性线索- NAcc神经元在信息退化线索开始时的敏感集合也将具有相同的效果。