The influence of mesolimbic-hippocampal interactions on episodic memory during active information seeking

项目摘要 海马和中脑边缘多巴胺系统之间的相互作用支持记忆编码， 随后巩固以稳定长期记忆中的显著信息。这些情节性的痕迹 支持各种自适应行为，包括推理、泛化和决策。 信息寻求进一步代表了一种情境，在这种情境中，动机性学习发生在缺乏外显知识的情况下。 奖励，包括孵化诱导的渴望和上下文相关的反馈。这样，信息搜索 可以作为一个模型来剖析中缘-海马回路如何有助于药物的复杂性， 寻求行为。大多数研究表明中缘-海马相互作用对 记忆集中在奖励上。然而，这种电路也与记忆增强密切相关 积极探索的结果。重要的是，在主动信息搜索过程中的记忆增强包括 跨事件的多个元素（线索与结果）的中脑边缘信号的整合， 时间尺度（事件诱发与状态依赖）。啮齿类动物的研究表明， 探索触发了一个正反馈回路，这增加了腹侧多巴胺信号的紧张性。 被盖区（VTA），这反过来又产生更大的VTA预期和反馈反应。特别是，这些 正反馈循环可以实例化和传播有助于物质使用的各种行为。 我们建议描述状态依赖性VTA响应如何与记忆增强相关， 使用新颖的行为范式、最先进的神经成像技术， 和计算建模来告知记忆的潜在机制。目标1将研究中脑边缘- 海马在主动学习和假设检验过程中参与记忆编码。目标2将研究 在编码过程中，这种回路的参与如何在后- 编码合并。最后，目标3将利用计算精神病学方法来研究个人如何 主动信息寻求期间的记忆差异与物质使用风险的预测因素有关。

PROJECT SUMMARY Interactions between the hippocampus and mesolimbic dopamine system supports memory encoding and subsequent consolidation to stabilize salient information in long-term memory. These episodic traces are used to support a variety of adaptive behaviors, including inference, generalization, and decision-making. Information seeking further represents a context in which motivated learning occurs in the absence of explicit reward, including incubation-induced craving and context-dependent feedback. In this way, information seeking may serve as a model to dissect how mesolimbic-hippocampal circuits contribute to the complexity of drug seeking behavior. Most research characterizing the contributions of mesolimbic-hippocampal interactions on memory have focused on reward. However, this circuit is also critically involved in memory enhancements resulting from active exploration. Critically, memory enhancements during active information seeking involves the integration of mesolimbic signaling across multiple elements of an event (cues versus outcomes) and timescales (event-evoked versus state-dependent). Rodent studies show that hippocampal engagement during exploration triggers a positive feedback loop, which increases tonic dopamine signaling in the ventral tegmental area (VTA), which in turn yields larger VTA anticipation and feedback responses. Prominently, these positive feedback loops could instantiate and propagate the variety of behaviors contributing to substance use. We propose to characterize how state-dependent VTA responses relate to memory enhancements during active information seeking using a combination of novel behavioral paradigms, state-of-the-art neuroimaging, and computational modeling to inform mechanisms underlying memory. Aim 1 will study mesolimbic- hippocampal contributes to memory encoding during active learning and hypothesis testing. Aim 2 will study how engagement of this circuit during encoding stabilizes memory representations during periods of post- encoding consolidation. Finally, Aim 3 will utilize a computational psychiatry approach to study how individual differences in memory during active information seeking relates to predictors of substance use risk.