Neural Basis of Temporal Order Memory

时间顺序记忆的神经基础

• 批准号: 8035440
• 负责人: Wendy A. Suzuki
• 金额: $ 37.19万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2015-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8035440
• 关键词: Address; Affect; Aging; Alzheimer' s Disease; Animals; Area; Behavior; Brain; Color; Computer Simulation; Cues; Disease; Dorsal; Employee Strikes; Episodic memory; Event; Foundations; Goals; Hippocampus (Brain); Impairment; Individual; Lateral; Learning; Maintenance; Medial; Memory; Memory Disorders; Memory impairment; Monitor; Nature; Pattern; Performance; Prefrontal Cortex; Process; Records Controls; Relative (related person); Retrieval; Role; Sampling; Schizophrenia; Series; Short-Term Memory; Signal Transduction; Site; Stimulus; Structure; Techniques; Temporal Lobe; Testing; Time; base; cognitive control; cognitive function; design; developmental disease; entorhinal cortex; extrastriate visual cortex; insight; long term memory; memory encoding; memory retrieval; neurophysiology; novel; prospective; public health relevance; relating to nervous system; research study; response; therapy development

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.

描述(由申请人提供)：情节记忆被定义为对个别事件或情节的细节丰富和灵活访问的记忆。情节记忆的一个关键组成部分是对情节中项目的时间顺序的记忆。虽然内侧颞叶(MTL)和前额叶(PFC)的结构都对时间顺序信息的记忆有贡献，但这种贡献的性质以及这些关键脑区在时间顺序记忆过程中的相互作用仍有待阐明。另一个未解决的问题是，这些区域对工作记忆的相对贡献，以及对时间有序信息的长期记忆任务。本实验基于这样一个基本假设，即时间顺序记忆的MTL和PFC对工作记忆和长时记忆任务的贡献是互补但不同的。为了验证这些假设，我们将进行一系列假设驱动的实验，旨在确定在需要工作记忆或长时记忆提取的时序任务中，MTL和PFC结构的具体贡献和相互作用。在具体目标1中，我们将分别和同时记录动物对物体执行工作记忆时序记忆任务时MTL和PFC中的活动。在特定的目标2中，我们将同时记录这两个区域，因为动物执行的任务需要对颜色-线索-时间顺序关联进行长期记忆。对于这两个目标，交叉相关分析以及LFP和尖峰场相干分析将使我们能够评估这些区域之间相互作用的时间和性质。具体地说，我们预测MTL的主要作用是在时序任务的WM和LTM版本期间，主要通过海马体的活动，为特定的试验事件和试验计时提供强烈的信号。此外，我们预测，在工作记忆任务中，周围的内嗅皮层和周边皮层参与了客体和客体-时间顺序连接词的助记编码，而周边皮质对于提取颜色线索和时间顺序之间的联系的长期记忆是至关重要的。相反，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维持时间顺序信息的突出作用，尽管我们可能在PFC中也看到与试验计时相关的活动。了解MTL和PFC在时序记忆中的特殊贡献和功能相互作用，不仅将对情景记忆的基本认知功能提供新的见解，而且对于开发各种影响情景记忆的疾病状态的治疗具有重要意义，包括阿尔茨海默病、精神分裂症和随着年龄增长而出现的记忆障碍。 公共卫生相关性：阿尔茨海默病、精神分裂症、发育障碍和衰老都涉及与内侧颞叶和/或前额叶皮质受损相关的学习和记忆障碍。在这里，我们建议使用神经生理记录技术来表征在不同的时间顺序记忆任务中，内侧颞叶和前额叶皮质结构之间的个体贡献和相互作用。这些信息将成为开发影响内侧颞叶、前额叶皮质及其相互作用的记忆障碍治疗方法的重要基础。