Neural Basis of Temporal Order Memory

时间顺序记忆的神经基础

• 批准号: 7887923
• 负责人: Wendy A. Suzuki
• 金额: $ 35.7万
• 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/7887923
• 关键词: Address; Affect; Age; 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）：情景记忆被定义为对单个事件或情节具有丰富细节和灵活存取的记忆。情景记忆的一个关键组成部分是对情节中事物的时间顺序的记忆。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大脑区域在时间顺序记忆中的相互作用仍有待阐明。这些区域对短时有序信息的工作记忆和长期记忆任务的相对贡献也未得到解决。我们提出的实验是基于一个基本假设，即颞叶颞叶和前皮层以互补但可区分的方式对工作记忆和长期记忆任务的表现做出贡献。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期记忆检索的时间顺序任务中，MTL和PFC结构的具体贡献和相互作用。在具体目标1中，我们将分别记录动物与物体执行工作记忆时间顺序记忆任务时MTL和PFC的活动。在具体目标2中，我们将同时记录动物在执行一项需要长期记忆的任务时的两个区域的颜色线索-时间顺序关联。对于这两个目标，相互关联分析以及LFP和峰场相干性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。具体来说，我们预测颞叶颞叶的一个主要作用，主要是通过海马体的活动，在WM和LTM版本的时间顺序任务中为特定的试验事件和试验时间提供强烈的信号。此外，我们预测周围的嗅内皮层和嗅周围皮层参与工作记忆任务中物体和物体-时间顺序连接词的记忆编码，并且嗅周围皮层对于提取颜色线索和时间顺序之间的关联的长期记忆至关重要。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持时间顺序信息的突出作用，尽管我们也可能在PFC中看到与试验时间相关的活动。了解MTL和PFC在时间顺序记忆中的具体作用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，而且对于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，这些疾病状态包括阿尔茨海默病、精神分裂症和衰老中的记忆障碍。