The role of medial striatum in spatial sequence learning

海马体(HPC)同时编码当前、过去和未来的位置；并区分 作为不同体验的一部分，在同一地点发生的事件。HPC活动的这些方面可能会 支持情景记忆，对个人经历的过去事件进行编码。然而，神经基质 支持使用这些情节记忆来实现灵活行为的方法仍然不够 理解，从而排除了记忆障碍治疗方法的发展。记忆的一种方式- 基于灵活的行为可以通过HPC和其他本地之间的活动的瞬时协调来产生 记忆网络，如背内侧纹状体(DSM)，参与行为灵活性，其 神经元以动作调节的方式放电(动作选择，AC)。这一系列研究的长期目标是 理解环境助记需求如何导致不同局部的瞬时功能耦合 以记忆电路来指导行为(记忆的动态模型)。当前的目标是 建议评估DSM对消除相同物理的重复遍历的歧义的贡献 不同旅程中的空间位置(顺序环境)，这是一项与HPC功能和情节相关的任务 记忆。当前提议的中心假设是，行为任务的结构调节 发生在同一空间的相似事件如何被区分为HPC-DSM中不同事件的一部分 网络。这项拟议的工作的基本原理是，确定神经回路如何使用存储 在类似但截然不同的情况下充分采取行动的信息将提供一个强有力的科学框架 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： 目的1.确定HPC和DSM活动在消除顺序语境歧义方面的作用。 这一目标的工作假设是，在HPC和DSM中结合神经放电是必要的 成功地区分了共享轨迹段的扩展空间序列。目标2.确定 与成功消除歧义相关的HPC/DSM神经活动模式 顺序上下文我们的工作假设是，尽管HPC不区分顺序上下文 上下文在第二个尺度上，在毫秒尺度上区分就地细胞的活动组合 与编码AC的DSM神经元的活动有关。我们预计拟议的研究结果将 证明了顺序语境歧义消除涉及神经网络，该神经网络包括 HPC和DSM(目标1)；分析神经活动的深层结构将揭示HPC是如何 当适当的动作涉及记忆时，表征与DSM活动相结合来指导行为 在同一环境中发生的不同的过去事件(目标2)。拟议的研究结果将 有助于充分理解情节记忆的神经基础，这对几个方面都有影响 神经和精神疾病，并将导致提交一份相当于R01的提案。

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.