Spatial Functions of the Medial Temporal Lobe

描述(申请人提供)：在内侧颞叶受损的健忘症患者中，神经可塑性的重要性最为明显。这些患者表现出深刻的、选择性的和持久的无法形成或保持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/关系存储器的一个典型形式是空间信息的存储器。这项提议的目标是定义猕猴海马体和内嗅觉皮质中空间信息记忆的两个重要方面所依据的神经活动模式。首先，我们的初步数据显示，海马神经元和大脑皮层神经元发出信号，学习新的空间关联(物体-位置关联任务)，神经活动的戏剧性变化称为“变化细胞”。具体目标1将定义学习对象-地点关联控制的哪一方面/S/S变化的细胞。这些研究将确定错误试验和对对象身份、位置特异性、运动反应和行为背景的系统操纵如何控制不断变化的细胞的活动。轨迹或行程的空间记忆的第二个关键方面(即如何从A点到B点)是记住事件在空间序列中的时间顺序的能力。特定目标2将在执行延迟序列回忆任务时检查海马体和内嗅觉皮质中的长期和工作记忆信号。在延迟序列回忆任务中，动物必须根据记忆再现三项序列的顺序。特定目标3将进一步将特定目标1和2中在海马体和内嗅皮层中识别的与任务相关和记忆相关的细胞归类为假定的兴奋性(PE)或快速峰波(FS)细胞。这些实验还将试图确定猴子海马体和浅层内嗅皮层中的明确theta活动。因此，后面的这些实验将允许我们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theta相联系，以及2)将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与在大鼠中观察到的关系进行比较。这些研究的结果对理解与记忆功能障碍有关的各种神经状态具有重要意义，包括阿尔茨海默病、癫痫和精神分裂症。

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.