Impact of cocaine on the Actor/Critic circuit

描述（由申请人提供）：演员/评论家模型被认为是优化长期收益的计算解决方案。在这个模型中，当结果偏离预期时，参与者做出的决策由评论家更新。过去的研究表明，中脑多巴胺（DA）神经元在奖励预测中发出错误信号；然而，尚不清楚这些信号是如何产生的，以及它们如何影响下游大脑区域的决策政策。根据Actor/Critic模型，中脑DA神经元通过比较腹侧纹状体（VS）发出的奖励预测值与实际收到的奖励值来计算预测误差，但这尚未得到直接测试。随后，预测误差被认为是通过更新行动者背侧纹状体（DS）的动作策略来改变行为的。退行性椎体学习中的神经相关因素包括与刺激、反应和结果相关的策略，但这些相关因素在学习过程中如何被数据处理系统调节尚不清楚。在这里，这些问题将通过分别记录DA和VS失活后DS和中脑DA神经元的单个神经元来解决。这些相互作用的重要性将通过失活技术得到验证。重要的是，这个回路在成瘾中被证明是不正常的，这是有道理的，考虑到成瘾者在面对变化的后果时不能优化选择行为。最后一项实验将检验长期自我服用可卡因的大鼠的奖励预测、预测误差和决策政策的神经相关性；研究结果将有助于确定长期药物暴露后这些神经表征是如何被破坏的。

DESCRIPTION (provided by applicant): The Actor/Critic model has been suggested to be the computational solution to optimizing long term gains. In this model, decisions made by the Actor are updated by the Critic when outcomes deviate from what is expected. Past research shows that midbrain dopamine (DA) neurons signal errors in reward prediction; however, it is unknown how these signals are generated or how they impact decision policies in downstream brains areas. According to the Actor/Critic model, midbrain DA neurons compute prediction errors by comparing the predicted value of reward, signaled by ventral striatum (VS), to the actual value of reward received, but this has not been directly tested. Subsequently, prediction errors are thought to modify behavior by updating the action policies of the Actor, dorsal striatum (DS). Neural correlates in DS include policies related to stimuli, responses and outcomes, but how these correlates are modulated by the DA system during learning remains unknown. Here, these issues will be addressed by recording from single neurons in DS and midbrain DA neurons after DA and VS inactivation, respectively. The importance of these interactions will be verified by inactivation techniques. Importantly, this circuit has been shown to be abnormal in addiction, which makes sense, considering that addicts cannot optimize choice behavior in the face of changing consequences. A final experiment will examine neural correlates of reward predictions, prediction errors and decision policies in rats that have chronically self-administered cocaine; the results will help determine how these neural representations are disrupted after long-term drug exposure.