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

主动信息寻求过程中中边缘-海马相互作用对情景记忆的影响

基本信息

批准号：
10621702
负责人：
Vishnu Pradeep Murty
金额：
$ 54.72万
依托单位：
TEMPLE UNIV OF THE COMMONWEALTH
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-05-15 至 2027-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10621702
关键词：
Active Learning Adaptive Behaviors Animal Model Behavior Behavior assessment Behavioral Behavioral Paradigm Cognitive Computer Models Corpus striatum structure Cues Decision Making Development Dopamine Elements Environment Episodic memory Event Feedback Functional Magnetic Resonance Imaging Future Hippocampus Human Incubated Individual Individual Differences Knowledge Learning Mediating Memory Modeling Motivation Outcome Perception Pharmaceutical Preparations Phase Pre-Clinical Model Process Psychiatry Psychological reinforcement Relapse Research Rewards Risk Risk Factors Rodent Sampling Shapes Signal Transduction Substance abuse problem Support System Testing Uncertainty Ventral Tegmental Area animal data contextual factors craving drug seeking behavior experience forgetting information processing information seeking behavior insight long term memory memory consolidation memory encoding mesolimbic system motivated behavior neuroimaging novel response substance use tool

项目摘要

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.

项目概要海马体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进行巩固以稳定长期记忆中的显着信息。这些情节痕迹被使用支持各种自适应行为，包括推理、概括和决策。信息寻求进一步代表了一种在缺乏明确信息的情况下发生动机学习的环境。奖励，包括孵化引起的渴望和上下文相关的反馈。这样，信息查找可以作为剖析中脑边缘-海马回路如何影响药物复杂性的模型寻求行为。大多数研究都描述了中脑边缘-海马相互作用对记忆集中在奖励上。然而，该电路也与记忆增强密切相关积极探索的结果。至关重要的是，主动信息搜索期间的记忆增强涉及中脑边缘信号在事件的多个元素（线索与结果）之间的整合时间尺度（事件诱发与状态相关）。啮齿动物研究表明，海马参与探索触发正反馈循环，从而增加腹侧的强直多巴胺信号传导被盖区 (VTA)，进而产生更大的 VTA 预期和反馈响应。突出的是，这些正反馈循环可以实例化和传播导致物质使用的各种行为。我们建议描述状态相关的 VTA 响应如何与记忆增强相关结合新颖的行为范式、最先进的神经影像学、和计算模型来告知记忆背后的机制。目标 1 将研究中脑边缘- 海马体有助于主动学习和假设检验期间的记忆编码。目标2将学习在编码过程中该电路的参与如何稳定后编码期间的记忆表示编码合并。最后，Aim 3 将利用计算精神病学方法来研究个体如何主动寻求信息期间的记忆差异与物质使用风险的预测因素有关。