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)：执行者/批评者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，批评者会更新参与者所做的决定。过去的研究表明，中脑多巴胺(DA)神经元在奖赏预测中发出错误信号；然而，这些信号是如何产生的，或者它们如何影响大脑下游区域的决策策略，目前尚不清楚。根据Actor/Critic模型，中脑DA神经元通过将腹侧纹状体(VS)发出的奖赏预测值与收到的奖赏实际值进行比较来计算预测误差，但这一点尚未得到直接测试。随后，预测误差被认为通过更新操作者背侧纹状体(DS)的动作策略来改变行为。DS中的神经关联包括与刺激、反应和结果相关的策略，但这些关联是如何在学习过程中被DA系统调制的仍不清楚。在这里，这些问题将通过记录分别在DA和VS失活后的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灭活技术得到验证。重要的是，这个回路已经被证明在上瘾方面是不正常的，这是有道理的，因为考虑到上瘾者在面对不断变化的后果时无法优化选择行为。最后一项实验将检查长期自我注射可卡因的大鼠的奖励预测、预测错误和决策策略之间的神经关联；结果将有助于确定长期吸毒后这些神经表征是如何被破坏的。