Impact of cocaine on the Actor/Critic circuit

可卡因对演员/评论家电路的影响

• 批准号: 8280446
• 负责人: MATTHEW R ROESCH
• 金额: $ 30.13万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8280446
• 关键词: Address; Affect; Animals; Area; Behavior; Brain; Brain region; Choice Behavior; Chronic; Cocaine; Corpus striatum structure; Decision Making; Dopamine; Dorsal; Drug Exposure; Drug usage; Electric Stimulation; Exposure to; Fire - disasters; Future; Human; Knowledge; Laboratories; Learning; Life; Midbrain structure; Modeling; Nature; Neurons; Outcome; Policies; Process; Rattus; Research; Response to stimulus physiology; Rewards; Self Administration; Self-Administered; Signal Transduction; Solutions; Stimulus; Task Performances; Techniques; Testing; Update; Ventral Striatum; Work; addiction; cocaine exposure; dopamine system; dopaminergic neuron; drug of abuse; flexibility; improved; neuromechanism; relating to nervous system; research study; response

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）：已建议演员/评论家模型是优化长期收益的计算解决方案。在此模型中，当结果偏离预期时，评论家会更新演员的决定。过去的研究表明，中脑多巴胺（DA）神经元在奖励预测中信号错误。但是，未知这些信号是如何产生的，或它们如何影响下游大脑区域的决策政策。根据演员/评论家的模型，中脑DA神经元通过比较腹侧纹状体（VS）信号的奖励值与收到的奖励的实际值来计算预测错误，但这尚未直接测试。随后，人们认为预测错误是通过更新演员背纹状体（DS）的动作策略来改变行为的。 DS中的神经相关性包括与刺激，响应和结果有关的政策，但是在学习过程中，这些相关性如何由DA系统调节。在这里，这些问题将通过分别在DA和DA和失活后的DS和Midbrain DA神经元中的单个神经元记录来解决。这些相互作用的重要性将通过失活技术来验证。重要的是，考虑到成瘾者无法在不断变化的后果时优化选择行为，这是有道理的，这是有道理的，这是有道理的。最后一个实验将检查具有长期自我管理可卡因的大鼠的奖励预测，预测错误和决策政策的神经相关性；结果将有助于确定在长期药物暴露后如何破坏这些神经表征。