Spatial Functions of the Medial Temporal Lobe

描述（由申请人提供）：神经可塑性的重要性在内侧颞叶损伤的失忆症患者中最为明显。这些患者表现出对事实和事件形成或保持新的长期记忆的深刻的、选择性的和长期的无能，在人类中称为陈述性记忆，在动物中称为关系记忆。陈述性/关系性记忆的一种原型形式是空间信息记忆。本研究的目的是确定猕猴海马体和内嗅皮层中空间信息记忆的两个重要方面的神经活动模式。首先，我们的初步数据表明，海马体和皮层神经元通过被称为“变化细胞”的神经活动的巨大变化，向新的空间关联（物体-地点关联任务）的学习发出信号。具体目标1将定义学习到的对象-地点关联的哪个方面控制着变化的细胞。这些研究将确定错误试验和系统操作的对象识别，地点特异性，运动反应和行为环境如何控制变化细胞的活动。关于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）是在空间序列中记住事件的时间顺序的能力。具体目标2将研究在执行延迟序列回忆任务时海马和内嗅皮层的长期和工作记忆信号，在该任务中动物必须从记忆中重现三个项目序列的顺序。特异性Aims 3将进一步将特异性Aims 1和特异性Aims 2中海马体和内嗅皮层中发现的任务相关和记忆相关细胞分类为假定的兴奋性（PE）或快速尖峰（FS）细胞。这些实验还将试图识别猴子海马体和浅内嗅皮层的清晰θ波活动。因此，这些后一种实验将使我们能够1)将具有特定任务相关或助记信号的细胞与特定细胞类型（即PE或FS细胞）和θ波相联系起来；2)比较在猴子和大鼠身上观察到的细胞类型/ θ波调制和神经反应之间的关系。这些研究的结果对理解与记忆功能障碍相关的各种神经状态（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.