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）信号传导因其在复发和 在成瘾的啮齿动物模型和人类中，渴望药物。一个普遍的看法是多巴胺神经元 腹侧对盖区域（VTA）向伏隔核（NACC）传达了预测误差， 如果错误报告了提示和奖励的观察值和期望值之间的差异。批判 假设预测错误是基于值，并且该想法已被用来解释如何 滥用通过劫持DA介导的价值学习来发挥其增强作用。但是，在大多数研究中 测量DA细胞活性和神经递质释放，值与另一个至关重要的变量混淆 学习：相互信息，或环境中线索在奖励中信号相对变化的程度 速度。因此，该项目的总体目标是研究信息理论的程度 学习的解释可以由中纹DA动力学捕获。行为操纵将使用 建立的方法是在提示和奖励之间诱导共同信息的变化与独立于 大鼠帕夫洛维亚调节期间的价值。 AIM 1中提出的实验将使用光纤光度法评估 VTA DA神经元中的大量活性和NACC中的DA释放是否基于编码预测错误 相互信息，以及与互助信息相互缩放的NACC神经元中的提示反应。目标2 将确定条件行为在提示之间降低相互信息时是否会减少 NACC中VTA细胞体或VTA轴突末端的光遗传学DA刺激。实验 AIM 3将评估光遗传学是否在瞬间抑制向NACC投射的VTA DA神经元 帕夫洛维亚信息损失将使条件行为免于消散，以及是否刺激提示 NACC神经元在信息衰落提示开始时的敏感集合也将产生相同的效果。