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: 10598030
• 负责人: Eric Garr
• 金额: $ 7.63万
• 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/10598030
• 关键词: Association Learning; Attention; Auditory; Axon; Behavior; Behavior Control; Belief; Cells; Communication; Corpus striatum structure; 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; Video Recording; addiction; cohort; conditioning; dopaminergic neuron; drug addiction therapy; drug craving; drug of abuse; experience; experimental study; insight; neural; neurotransmitter release; novel therapeutics; optogenetics; postsynaptic; 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.

项目总结 腹侧纹状体中的多巴胺(DA)信号已受到相当大的关注，因为它在复发和 毒瘾，无论是在上瘾的啮齿动物模型中还是在人类中都是如此。一种流行的看法是，大脑中的多巴胺神经元 腹侧被盖区(VTA)将预测误差传递给伏隔核核心(NAcc)， 其中误差报告了线索和奖励的观测值和期望值之间的差值。一位批评者 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 滥用通过劫持DA中介的价值学习来发挥其强化作用。然而，在大多数研究中， 测量DA细胞活动和神经递质释放，值与另一个关键变量混淆 学习：相互信息，或环境中的线索发出奖赏相对变化的信号的程度 费率。因此，这个项目的总体目标是调查一个信息论 学习的描述可以通过纹状体中脑区的动态变化来捕捉。行为操控将利用 建立的诱导线索和奖励之间的互信息变化的方法独立于 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神经元的整体活动和NAcc中的DA释放是否编码了基于 相互信息，以及NAcc神经元中的线索诱发反应是否随着相互信息的变化而变化。目标2 将决定条件性行为在降低线索之间的相互信息时是否会减少 NAcc内VTA胞体或VTA轴突终末的光生DA刺激。实验在 Aim 3将评估在瞬间投射到NAcc的VTA DA神经元是否受到光遗传抑制 巴甫洛夫信息丢失将拯救条件性行为的消散，以及是否刺激线索- 在信息退化提示开始时，NAcc神经元的敏感集合也将产生同样的效果。