Neural Basis of Temporal Order Memory

描述（由申请人提供）：情节记忆被定义为对单个事件或情节的细节丰富且可灵活访问的记忆。情景记忆的一个关键组成部分是对情景中项目的时间顺序的记忆。虽然内侧颞叶（MTL）和前额叶皮层（PFC）的结构都有助于记忆时间顺序信息，但这种贡献的性质以及这些关键脑区在时间顺序记忆中的相互作用仍有待阐明。同样未解决的是，这些区域对工作记忆和长时记忆任务的相对贡献。本实验基于一个基本假设，即MTL和PFC对工作记忆和长时记忆任务中的时间顺序记忆的作用是互补的，但两者的作用方式是不同的。为了验证这些假设，我们将进行一系列的假设驱动的实验，旨在确定具体的贡献和相互作用的结构在MTL和PFC在时间顺序任务需要工作记忆或长期记忆检索。在具体目标1中，我们将记录活动的MTL和PFC都单独和同时作为动物执行工作记忆的时间顺序记忆任务的对象。在具体目标2中，我们将同时记录两个区域，因为动物执行一项需要长期记忆的任务，用于颜色-线索-时间顺序关联。对于这两个目标，互相关分析以及LFP和尖峰场的相干性分析将使我们能够评估这些领域之间的相互作用的时间和性质。具体来说，我们预测，MTL的主要作用，主要是通过海马体的活动，是提供强有力的信号，特别是审判事件和审判时间在WM和LTM版本的时间顺序任务。此外，我们预测，周围的内嗅皮层和嗅周皮层从事记忆编码的对象和对象的时间顺序连接的工作记忆任务和嗅周皮层是至关重要的检索的长期记忆之间的关联颜色线索和时间顺序。相比之下，我们假设PFC主要参与认知控制过程，包括在工作记忆延迟期间维护时序信息的重要作用，尽管我们也可能在PFC中看到与时间相关的活动。了解MTL和PFC在时间顺序记忆中的具体贡献和功能相互作用，不仅将为情景记忆的基本认知功能提供新的见解，而且对开发各种影响情景记忆的疾病状态的治疗方法具有重要意义，包括阿尔茨海默病，精神分裂症和衰老中存在的记忆障碍。 公共卫生相关性：阿尔茨海默氏病、精神分裂症、发育障碍和衰老都涉及与内侧颞叶和/或前额叶皮质损伤相关的学习和记忆障碍。在这里，我们建议使用神经生理学记录技术来表征个体的贡献和内侧颞叶和前额叶皮层的结构之间的相互作用，在各种任务的时间顺序记忆。这一信息将成为发展影响内侧颞叶、前额叶皮层及其相互作用的记忆障碍治疗方法的重要基础。

DESCRIPTION (provided by applicant): 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 hypotheses, 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. PUBLIC HEALTH RELEVANCE: Alzheimer's disease, schizophrenia, developmental disorders and aging all involve impairments in learning and memory associated with damage to the medial temporal lobe and/or the prefrontal cortex. Here we propose to use neurophysiological recording techniques to characterize the individual contributions and interactions between the structures of the medial temporal lobe and the prefrontal cortex during various tasks of temporal order memory. This information will serve as an important foundation for the development of treatments for disorders of memory that affect the medial temporal lobe, the prefrontal cortex and their interactions.