Spatial Functions of the Medial Temporal Lobe

描述（由申请人提供）：没有什么地方比内侧颞叶受损的健忘症患者更明显的神经可塑性的意义。这些患者表现出深刻的，选择性的和持久的无法形成或保留对事实和事件的新的长期记忆，称为人类的陈述性记忆和动物的关系记忆。陈述性/关系性记忆的一种典型形式是空间信息记忆。本研究的目的是确定猕猴海马和内嗅皮层中两个重要的空间信息记忆方面的神经活动模式。首先，我们的初步数据表明，海马和皮层神经元信号学习新的空间协会（对象-位置关联任务）与戏剧性的变化，在神经活动称为“变化的细胞”。具体目标1将定义学习的对象-位置关联的哪个方面控制变化的单元格。这些研究将确定错误试验和对象身份，位置特异性，运动反应和行为背景的系统操作如何控制变化细胞的活动。轨迹或旅程的空间记忆的第二个关键方面（即，如何从A点到达B点）是记住事件在空间序列中的时间顺序的能力。具体目标2将检查海马和内嗅皮层中的长期和工作记忆信号，在延迟序列回忆任务的执行过程中，动物必须从记忆中重现三项序列的顺序。具体目标3将进一步将具体目标1和2中在海马和内嗅皮层中鉴定的任务相关和记忆相关细胞分类为假定的兴奋性（PE）细胞或快速尖峰（FS）细胞。这些实验还将试图识别猴子海马体和浅表内嗅皮层中明确的θ活动。因此，这些后面的实验将允许我们1）将具有特定任务相关或记忆信号的细胞与特定细胞类型（即，PE或FS细胞）和θ相位之间的关系，以及2）将在猴中观察到的细胞类型/θ调制和神经反应之间的关系与在大鼠中描述的关系进行比较。这些研究的结果对于理解与记忆功能障碍相关的各种神经系统状态，包括阿尔茨海默病，癫痫和精神分裂症具有重要意义。

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.