Spatial Functions of the Medial Temporal Lobe

内侧颞叶的空间功能

• 批准号: 6917167
• 负责人: Wendy A. Suzuki
• 金额: $ 30.34万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917167
• 关键词: Macaca mulatta; autoradiography; behavior test; behavioral /social science research tag; brain electrical activity; brain mapping; cues; entorhinal cortex; histology; injection /infusion; learning; long term memory; magnetic resonance imaging; microelectrodes; neural information processing; neural plasticity; neurons; performance; radiotracer; short term memory; space perception; temporal lobe /cortex; visual stimulus

DESCRIPTION (provided by applicant): Nowhere is the significance of neural plasticity more evident than in amnesic patients with damage to the medial temporal lobe. These patients exhibit a profound, selective and long-lasting inability to form or retain new long-term memory for facts and events, termed declarative memory in humans and relational memory in animals. One prototypical form of declarative/relational memory is memory for spatial information. The goal of this proposal is to define the patterns of neural activity that underlie 2 important aspects of memory for spatial information in the macaque monkey hippocampus and entorhinal cortex. First, our preliminary data show that hippocampal and cortical neurons signal learning of new spatial associations (object-place association task) with dramatic changes in neural activity termed "changing cells". Specific Aim 1 will define which aspect/s of the learned object-place association control/s the changing cells. These studies will determine how error trials and systematic manipulations of object identity, place specificity, motor response and behavioral context control the activity of the changing cells. A second key aspect of spatial memory for trajectories or journeys (i.e., how to get from point A to point B) is the ability to remember the temporal order of events in a spatial sequence. Specific Aim 2 will examine both the long-term and working memory signals in the hippocampus and entorhinal cortex during the performance of a delayed sequence recall task where animals must reproduce the order of three-item sequences from memory. Specific Aim 3 will further categorize the task-related and memory-related cells identified in the hippocampus and entorhinal cortex in Specific Aims 1 and 2 into either putative excitatory (PE) or fast spiking (FS) cells. These experiments will also attempt to identify clear theta activity in the monkey hippocampus and superficial entorhinal cortex. Thus, these latter experiments will allow us to 1) link cells with particular task-related or mnemonic signals to specific cell types (i.e., PE or FS cells) and phases of theta and 2) compare the relationship between cell type/theta modulation and neural response observed in monkeys to that described in rats. The results from these studies have implications for understanding a variety of neurological states associated with memory dysfunction including Alzheimer's disease, epilepsy and schizophrenia.

描述（由申请人提供）：与内侧颞叶受损的健忘症患者相比，神经可塑性的重要性更重要。这些患者表现出深刻的，有选择性和长期的无法形成或保留事实和事件的新长期记忆，这些记忆被称为人类的声明性记忆和动物的关系记忆。声明性/关系记忆的一种典型形式是空间信息的内存。该提案的目的是定义神经活动的模式，该模式是2个重要方面的记忆，用于猕猴海马和内嗅皮层中的空间信息的重要方面。首先，我们的初步数据表明，新空间关联（对象位置关联任务）的海马和皮质神经元信号学习，其神经活动的急剧变化称为“改变细胞”。特定的目标1将定义学习对象位置关联的哪个方面/s控制不断变化的单元格。这些研究将确定错误试验和系统操纵如何对物体身份，放置特异性，运动响应和行为环境控制不断变化的细胞的活性。轨迹或旅行空间内存的第二个关键方面（即，如何从a到b点获得）是记住空间序列中事件的时间顺序的能力。在延迟序列召回任务的过程中，特定的目标2将检查海马和内嗅皮层中的长期和工作记忆信号，其中动物必须从记忆中重现三个项目序列的顺序。特定的目标3将进一步将特定目标1和2中海马和内嗅皮层中与任务相关的与内存相关的细胞分类为假定的兴奋性（PE）或快速尖峰（FS）细胞。这些实验还将试图鉴定猴海马和浅表内嗅皮层中的清晰theta活性。因此，这些后一个实验将允许我们到1）将细胞与特定任务相关或助记符信号与特定细胞类型（即PE或FS细胞）以及theta的相结合，以及2）比较猴子在猴子中观察到的细胞类型/theta调制和神经反应之间的关系。这些研究的结果对了解与记忆功能障碍有关的各种神经系统具有影响，包括阿尔茨海默氏病，癫痫和精神分裂症。