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

项目总结 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和 随后的巩固，以稳定长期记忆中的显著信息。这些插曲痕迹被用来 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背景，在这种背景下，动机学习发生在没有外显的情况下 奖励，包括孵化诱导的渴望和上下文相关的反馈。通过这种方式，信息搜索 可以作为一个模型来剖析中脑边缘-海马区环路如何影响药物的复杂性 寻求行为。大多数研究表征了中脑边缘-海马区相互作用对 记忆一直集中在奖励上。然而，这一电路也与记忆增强密切相关 由于积极探索而产生的。关键的是，在主动寻找信息的过程中记忆增强涉及到 整合跨事件多个元素的边缘中信号(线索与结果)和 时间尺度(事件引发的与状态相关的)。啮齿动物研究表明，海马区在 探索触发了正反馈环路，这增加了腹侧的紧张性多巴胺信号 被盖区(VTA)，这反过来又产生更大的VTA预期和反馈反应。值得注意的是，这些 正反馈环可以实例化和传播有助于物质使用的各种行为。 我们建议表征状态依赖的VTA响应如何与在 使用新的行为范式、最先进的神经成像、 和计算建模，以告知潜在的记忆机制。目标1将研究中边缘- 在主动学习和假设检验过程中，海马体参与记忆编码。目标2将研究 在编码过程中此电路的参与如何在POST期间稳定记忆表征 编码整合。最后，目标3将利用计算精神病学的方法来研究个体如何 主动寻找信息时记忆的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.