Ventral striatal processing of prefrontal inputs and phasic dopamine during rule switching

规则切换过程中前额叶输入和阶段性多巴胺的腹侧纹状体处理

• 批准号: 265323688
• 负责人: Dr. Florian Bähner
• 金额: --
• 依托单位: Klinik für Psychiatrie und Psychotherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/265323688?language=en
• 关键词: Ventral; striatal; processing; prefrontal; inputs

In novel situations individuals often learn through feedback which cues predict reward. Information about actions and their consequences needs to be updated whenever rules switch. Rule switching and the involved brain circuits are conserved across mammals. These brain circuits contain the nucleus accumbens (NAc) of the ventral striatum and the medial prefrontal cortex (mPFC). Dopamine (DA) transients both predict rewards and suppress interactions of mPFC and NAc. We will focus on the NAc that has been proposed to serve as a central gateway where converging inputs help to optimize reward outcome. Yet, the neuronal mechanisms of rule switching are largely unknown. To study the neural correlates of rule switching in freely moving rats, we propose to perform tetrode recordings and fast scan cyclic voltammetry in NAc and mPFC during performance of an operant version of a strategy set shifting paradigm. Experiments will be guided by two hypotheses. First, mPFC representations of a novel rule are integrated in the NAc to optimize reward outcome. We predict that mPFC-NAc interactions transiently increase after the rule switch when the animal has not yet learned the novel rule. To determine interactions of mPFC and NAc, coordinated firing of neuronal assemblies and their temporal organization by oscillations will be examined. Second, cues that predict reward elicit DA transients. We hypothesize that after the rule has switched, the old cue does not predict reward anymore and therefore stops eliciting DA transients. Artificially maintaining the DA signal concurrent with the old cue will thus prevent behavioral rule switches. These artificial DA transients are also predicted to suppress mPFC-NAc interactions. Towards these aims, we will initially examine the relation of the phasic DA transients in the NAc to behavioral performance and neuronal activity in the NAc during rule switching. In a second set of experiments, after the rule switch, the DA transient will be artificially restored concurrent with the now unrewarded cue using optogenetic stimulation of DAergic neurons. During this manipulation we will track behavioral performance and mPFC-NAc interactions. Together, our project shall help to understand the role of DA transients in rule switches and associated NAc representations. These findings have implications for cognitive flexibility that is impaired in major neuropsychiatric disorders.

在新的情况下，个人经常通过反馈来学习，这些反馈可以预测奖励。每当规则发生变化时，有关操作及其后果的信息都需要更新。规则转换和相关的大脑回路在哺乳动物中是保守的。这些大脑回路包含腹侧纹状体的伏隔核 (NAc) 和内侧前额皮质 (mPFC)。多巴胺 (DA) 瞬变既可以预测奖励，又可以抑制 mPFC 和 NAc 的相互作用。我们将重点关注 NAc，它被提议作为中央网关，汇聚输入有助于优化奖励结果。然而，规则转换的神经机制在很大程度上还是未知的。为了研究自由移动大鼠规则切换的神经相关性，我们建议在执行策略集转换范式的操作版本期间，在 NAc 和 mPFC 中进行四极记录和快速扫描循环伏安法。实验将由两个假设指导。首先，将新规则的 mPFC 表示集成到 NAc 中以优化奖励结果。我们预测，当动物尚未学会新规则时，规则切换后 mPFC-NAc 相互作用会短暂增加。为了确定 mPFC 和 NAc 的相互作用，将检查神经元组件的协调放电及其通过振荡的时间组织。其次，预测奖励的线索会引发 DA 瞬变。我们假设规则切换后，旧提示不再预测奖励，因此停止引发 DA 瞬变。因此，人为地维持 DA 信号与旧提示同步将防止行为规则切换。这些人工 DA 瞬态也预计会抑制 mPFC-NAc 相互作用。为了实现这些目标，我们将首先检查规则切换期间 NAc 中的相位 DA 瞬变与 NAc 中的行为表现和神经元活动的关系。在第二组实验中，规则切换后，使用 DAergic 神经元的光遗传学刺激，将 DA 瞬态与现在未奖励的提示同时人工恢复。在此操作过程中，我们将跟踪行为表现和 mPFC-NAc 相互作用。总之，我们的项目将有助于理解 DA 瞬态在规则切换和相关 NAc 表示中的作用。这些发现对主要神经精神疾病中受损的认知灵活性具有影响。