Neural Basis of Temporal Order Memory

情节记忆被定义为对个别事件或事件的细节丰富和灵活访问的记忆 剧集。情节记忆的一个关键组成部分是对一个事件中项目的时间顺序的记忆 这一集。很明显，内侧颞叶(MTL)和前额叶的结构 大脑皮质(PFC)都有助于记忆时间有序的信息，其本质是 时序记忆过程中关键脑区的贡献及相互作用 仍有待阐明。同样悬而未决的是这些领域对工作的相对贡献 对时间有序信息的记忆任务与长时记忆任务。建议数 实验的基础假设是MTL和PFC在 补充但不同的方式对工作记忆和长时间记忆的表现 时间顺序记忆的术语记忆任务。为了检验这些假设，我们将进行一系列 以假设为导向的实验，旨在定义 在需要工作记忆或时间顺序任务期间的MTL和PFC中的结构 长时记忆提取。在具体目标1中，我们将记录MTL和PFC中的活动 当动物单独和同时执行工作记忆时序记忆任务 使用对象。在特定目标2中，我们将在动物表演时同时记录这两个区域 这是一项需要长期记忆才能将颜色-线索-时间顺序联系起来的任务。为了这两个目标， 互相关分析以及LFP和尖峰场相干分析将使我们能够 评估这些领域之间相互作用的时机和性质。具体来说，我们预测 MTL的一个主要作用，主要是通过海马体的活动，提供强大的 在WM和LTM版本期间的特定试验事件和试验定时的信号 时序任务。此外，我们预测周围的内嗅觉皮质和虹膜周围皮质 从事宾语和宾语时间顺序连词的助记编码工作 记忆任务和大脑周围皮质对长时记忆的提取至关重要 颜色线索和时间顺序之间的联系。相反，我们假设PFC是 主要参与认知控制过程，包括在维持 工作记忆延迟期的时间顺序信息，尽管我们可能会看到试验 PFC中与时间相关的活动以及了解具体的贡献和功能 时间顺序记忆中MTL和PFC的相互作用不仅将为我们提供新的洞察力 情景记忆的基本认知功能，也具有重要的意义 影响情景记忆的多种疾病状态的治疗方法的发展 包括阿尔茨海默氏症、精神分裂症和随着年龄增长而出现的记忆障碍。

Episodic memory is defined as detail-rich and flexibly accessible memory for individual events or episodes. A key component of episodic memory is memory for the temporal order of items within an episode. While it is clear that the structures of the medial temporal lobe (MTL) and the prefrontal cortex (PFC) both contribute to memory for temporally ordered information, the nature of that contribution and the interactions between these key brain areas during temporal order memory remains to be elucidated. Also unresolved is the relative contribution of these areas to working memory versus long-term memory tasks for temporally ordered information. The proposed experiments are based on the underlying hypothesis that the MTL and PFC contribute in complementary but differentiable ways to the performance of both working memory and long- term memory tasks for temporal order memory. To test these hypothesis, we will conduct a series of hypothesis driven experiments designed to define the specific contributions and interactions of structures in the MTL and PFC during temporal order tasks requiring either working memory or long-term memory retrieval. In Specific Aim 1, we will record activity in the MTL and PFC both individually and simultaneously as animals perform a working memory temporal order memory task with objects. In Specific Aim 2, we will record simultaneously across both areas as animals perform a task requiring long-term memory for color-cue - temporal order associations. For both Aims, cross correlation analyses as well as LFP and spike-field coherence analyses will allow us to evaluate the timing and the nature of the interactions between these areas. Specifically, we predict that a major role of the MTL, mainly through the activity of the hippocampus, is to provide strong signals for particular trial events and trial timing during both the WM and the LTM versions of the temporal order task. In addition, we predict that the surrounding entorhinal and perirhinal cortex are engaged in mnemonic encoding of object and object-temporal order conjunctions for the working memory task and the perirhinal cortex is critical for the retrieval of the long-term memory for associations between color-cues and temporal order. In contrast, we hypothesize that the PFC is primarily involved in cognitive control processes including a prominent role in maintenance of temporal order information during the working memory delay period, though we may see trial timing-related activity in the PFC as well Understanding the specific contributions and functional interactions of the MTL and PFC in temporal order memory will not only provide new insight into the fundamental cognitive function of episodic memory, but also has important implications for the development of treatments for a wide variety of disease states that affect episodic memory including Alzheimer's disease, schizophrenia, and the memory impairments present in aging.