The role of medial striatum in spatial sequence learning

内侧纹状体在空间序列学习中的作用

• 批准号: 10727401
• 负责人: Janina Diana Ferbinteanu
• 金额: $ 43.18万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10727401
• 关键词: Alzheimer' s Disease; Animal Model; Animals; Area; Behavior; Behavioral; Brain; Cells; Cognitive; Collection; Compensation; Complement; Complex; Corpus striatum structure; Coupling; Dimensions; Dorsal; Environment; Episodic memory; Event; Fire - disasters; Future; Goals; Hippocampus; Huntington Disease; Impairment; Learning; Link; Literature; Location; Medial; Memory; Memory Disorders; Mental Depression; Mental disorders; Modeling; Monitor; Motor; Neurologic; Neurons; Organism; Outcome; Output; Pattern; Post-Traumatic Stress Disorders; Prefrontal Cortex; Public Health; Records; Research; Rewards; Role; Schizophrenia; Structure; Temporal Lobe; Testing; Time; Work; Yin; autism spectrum disorder; environmental change; experience; experimental study; flexibility; human model; insight; millisecond; neural; neural circuit; neural network; place fields; prefrontal lobe; response; sequence learning; theories; therapy development; way finding

The hippocampus (HPC) encodes concomitantly current, past and future locations; and distinguishes between events that occur in the same place as part of distinct experiences. These aspects of HPC activity are likely to support episodic memory, which encodes personally experienced past events. However, the neural substrate that supports the use of these episodic memories to achieve flexible behavior remains insufficiently understood, precluding thus the development of treatments in memory disorders. One way in which memory- based flexible behavior may be generated is by transient coordination of activity between HPC and other local memory networks such as dorso-medial striatum (DSM) which is involved in behavioral flexibility and whose neurons fire in action-modulated manner (action choice, AC). The long-term goal of this line of research is to understand how circumstantial mnemonic demand may lead to transient functional coupling of distinct local memory circuits in order to guide behavior (the dynamic model of memory). The objective of the current proposal is to evaluate the contribution of DSM to disambiguation of repeated traversals of the same physical spatial locations while on distinct journeys (sequential context), a task relevant for HPC function and episodic memory. The central hypothesis of the current proposal is that the structure of the behavioral task modulates how similar events that occur in the same space are distinguished as part of different episodes in the HPC-DSM network. The rationale of the proposed work is that a determination of how neural circuits use stored information to act adequately in similar but yet distinct circumstances will offer a strong scientific framework whereby new strategies in memory research can be developed.. We propose the following two specific aims: Aim 1. Identify the roles of HPC and DSM activities in disambiguation of sequential contexts. The working hypothesis of this aim is that a combination of neural firing in both HPC and DSM is necessary to successfully distinguish the extended spatial sequences that share segments of trajectory. Aim 2. Identify the HPC/DSM neural activity patterns that are correlated with successful disambiguation of sequential contexts Our working hypothesis is that although HPC does not differentiate between sequential contexts at the second scale, distinction is made at the millisecond scale in place cells' activity in combination with the activity of DSM neurons which encode AC. We expect the results of the proposed research to demonstrate that that disambiguation of sequential contexts involves a neural network encompassing both HPC and DSM (Aim 1); and that analyzing the deep structure of neural activity will uncover how the HPC representation combines with DSM activity to guide behavior when appropriate action involves memory of distinct past events that occurred in the same environment (Aim 2). The results of the proposed research will contribute to fully understanding the neural basis of episodic memory, which has implications for several neurological and mental illnesses, and will lead to submission of an R01-equivalent proposal.

海马体（HPC）编码伴随当前，过去和未来的位置;并区分 发生在同一地点的事件，作为不同经历的一部分。HPC活动的这些方面可能会 支持情景记忆，编码个人经历的过去事件。然而，神经基质 支持使用这些情景记忆来实现灵活行为的证据仍然不足 因此，排除了记忆障碍治疗的发展。其中一种记忆- 基于灵活的行为可以通过HPC和其他本地设备之间的活动的瞬时协调来生成。 记忆网络，如背内侧纹状体（DSM），其涉及行为灵活性， 神经元以动作调制的方式（动作选择，AC）放电。这项研究的长期目标是 理解环境记忆需求如何导致不同局部的瞬时功能耦合 记忆电路，以指导行为（记忆的动态模型）。当前的目标 建议是评估DSM的贡献，消除歧义的重复遍历相同的物理 空间位置，而在不同的旅程（顺序上下文），一个任务相关的HPC功能和情节 记忆当前提议的中心假设是，行为任务的结构调节 在HPC-DSM中，如何将发生在同一空间的相似事件区分为不同事件的一部分 网络这项工作的基本原理是， 在类似但不同的情况下采取适当行动的信息将提供强有力的科学框架 由此可以开发记忆研究的新策略。我们提出以下两个具体目标： 目标1.确定HPC和DSM活动在顺序上下文消歧中的作用。 这一目标的工作假设是，HPC和DSM中的神经放电的组合是必要的， 成功区分共享轨迹段的扩展空间序列。目标二。识别 HPC/DSM神经活动模式与成功消除 我们的工作假设是，虽然HPC不区分顺序上下文， 在第二个尺度上，在毫秒尺度上区分位置细胞的活动组合 与编码AC的DSM神经元的活动有关。我们希望拟议研究的结果， 证明了顺序上下文的消歧涉及到一个神经网络， HPC和DSM（目标1）;分析神经活动的深层结构将揭示HPC如何 当适当的行动涉及记忆时， 在同一环境中发生的不同的过去事件（目标2）。拟议研究的结果将 有助于充分理解情景记忆的神经基础，这对几个方面都有影响。 神经和精神疾病，并将导致提交R 01等效提案。