Impact of cocaine on the Actor/Critic circuit

可卡因对演员/评论家电路的影响

基本信息

批准号：
8459880
负责人：
MATTHEW R ROESCH
金额：
$ 31.49万
依托单位：
UNIV OF MARYLAND, COLLEGE PARK
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2016-04-30
项目状态：
已结题

项目摘要

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.

描述（由申请人提供）：Actor/Critic 模型已被建议作为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，Critic 会更新 Actor 做出的决策。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，目前尚不清楚这些信号是如何产生的，或者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 神经元通过将腹侧纹状体 (VS) 发出的奖励预测值与收到的奖励的实际值进行比较来计算预测误差，但这尚未经过直接测试。随后，预测错误被认为可以通过更新行动者背侧纹状体（DS）的行动策略来改变行为。 DS 中的神经关联包括与刺激、反应和结果相关的策略，但在学习过程中 DA 系统如何调节这些关联仍然未知。在这里，这些问题将通过分别在 DA 和 VS 失活后记录 DS 和中脑 DA 神经元中的单个神经元来解决。这些相互作用的重要性将通过灭活技术来验证。重要的是，这一回路已被证明在成瘾中是异常的，考虑到成瘾者在面对不断变化的后果时无法优化选择行为，这是有道理的。最后的实验将检查长期自我注射可卡因的老鼠的奖励预测、预测错误和决策策略的神经相关性。研究结果将有助于确定这些神经表征在长期接触药物后是如何被破坏的。