Mesostriatal dopamine in Pavlovian reward rate learning

项目概要 腹侧纹状体中的多巴胺 (DA) 信号传导因其在复发和复发中的作用而受到广泛关注。 对药物的渴望，无论是在成瘾啮齿类动物模型中还是在人类中。人们普遍认为，多巴胺神经元 腹侧被盖区（VTA）将预测误差传达给伏隔核核心（NAcc）， 其中错误报告了提示和奖励的观察值和预期值之间的差异。一个批评的 假设是预测误差是基于值的，这个想法已被用来解释药物如何 滥用通过劫持 DA 介导的价值学习来发挥强化作用。然而，在大多数研究中 测量 DA 细胞活性和神经递质释放，该值与另一个关键变量混淆 学习：相互信息，或者环境中的线索发出奖励相对变化的程度 率。因此，该项目的总体目标是调查信息论的程度 学习的说明可以通过中纹状体 DA 动态来捕获。行为操纵将利用 建立了诱导线索和奖励之间相互信息变化的方法，独立于 大鼠巴甫洛夫条件反射期间的值。目标 1 中提出的实验将使用光纤光度测定法来评估 VTA DA 神经元的大量活动和 NAcc 中的 DA 释放是否编码预测误差 互信息，以及 NAcc 神经元中提示诱发的反应是否与互信息成比例。目标2 将确定当线索之间的相互信息退化时条件行为是否会减少 以及 VTA 细胞体或 NAcc 中 VTA 轴突末端的光遗传学 DA 刺激。实验于 目标 3 将评估是否光遗传学抑制在瞬间投射到 NAcc 的 VTA DA 神经元 巴甫洛夫信息丢失将挽救条件行为免于消散，以及是否刺激提示 在信息退化线索开始时，NAcc 神经元的敏感集合也会产生相同的效果。

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.