The Neural Basis of Relational Memory

描述（由申请人提供）：记忆受损是阿尔茨海默病、颞叶癫痫、抑郁症和精神分裂症等疾病的重要组成部分，这些疾病共同影响着2000多万美国人。我们的长期目标是更好地理解记忆过程背后的神经机制，从而使我们更接近为这些残疾患者开发新的治疗方法。这一建议的目的是阐明海马体在关系记忆中的作用。关系记忆是指将场景或事件要素之间的任意或偶然关系联系在一起的能力。然而，目前还没有证据表明灵长类动物海马在单个神经元或神经元群水平上存在关系记忆信号。猴子可以被测试一些与人类受试者非常相同的关系记忆任务，因此，对猴子海马体中单个单元和神经元网络活动的神经生理学研究将有助于确定关系记忆基础的神经元表征的本质。基于初步数据，我们假设海马体中的单个神经元和同步神经元群在活动中表现出可能用于关系记忆的调节。本文提出的实验将直接验证这一假设，使用多电极记录参与一系列关系记忆任务的猴子海马的尖峰活动和局部场电位（LFP），这些实验改编自人类文献。我们将研究关于关系记忆性能的单单元放电率和spike-field神经元同步的调制，包括各种领域，例如空间，上下文和时间。此外，为了评估这些海马体电生理相关是否对关系记忆过程至关重要，或者这些过程是否也可以在缺乏功能性海马体的情况下由内侧颞叶皮质区支持，我们将测试海马体受限病变对这些相同的关系记忆任务的影响。这些实验有以下潜在的结果：1)确定灵长类动物海马中神经元活动的变化，这些变化表明了关系联想的学习；2)确定神经元同步是关系记忆表现的可能机制；3)解决人类病变研究中关于海马在关系记忆中的作用的明显不一致。

DESCRIPTION (provided by applicant): Impaired memory is an important component of diseases such as Alzheimer's disease, temporal lobe epilepsy, depression, and schizophrenia that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. The objective of this proposal is to clarify the role of the hippocampus in relational memory. Relational memory refers to the ability to link together the arbitrary or accidental relations among elements of scenes or events. However, there is currently little evidence for relational memory signals in the primate hippocampus at the level of individual neurons or groups of neurons. Monkeys can be tested on some of the very same relational memory tasks as human subjects, and, therefore, neurophysiological studies of the activity of single units and neuronal networks in the monkey hippocampus will be instrumental in identifying the nature of neuronal representations that underlie relational memory. Based on preliminary data, we hypothesize that single neurons and synchronized ensembles of neurons in the hippocampus display modulations in activity that may be used for relational memory. The experiments proposed here will directly test this hypothesis, using multi-electrode recordings of spiking activity and the local field potential (LFP) in the hippocampus of monkeys engaged in a battery of relational memory tasks, adapted from the human literature. We will examine modulations in single-unit firing rates and spike-field neuronal synchronization with respect to relational memory performance encompassing a variety of domains, e.g., spatial, contextual, and temporal. In addition, to assess whether these hippocampal electrophysiological correlates are critical for relational memory processes or whether these processes could also be supported by medial temporal cortical areas in the absence of a functional hippocampus, we will test the effects of restricted lesions of the hippocampus on these same relational memory tasks. The proposed experiments have the following potential outcomes: 1) to determine the changes in neuronal activity in the primate hippocampus that signal the learning of relational associations, 2) to identify neuronal synchronization as a possible mechanism underlying relational memory performance, and 3) to resolve the apparent inconsistencies among human lesion studies regarding the role of the hippocampus in relational memory. PUBLIC HEALTH RELEVANCE: Impaired memory is an important component of diseases such as temporal lobe epilepsy, depression, schizophrenia, and Alzheimer's disease that collectively affect over twenty million Americans. Our long-range goal is to contribute to a better understanding of the neural mechanisms that underlie memory processes, in order to bring us closer to developing new therapies for these disabled patients. The objective of this proposal is to identify neural mechanisms in the hippocampus that may underlie relational memory and to determine whether the hippocampus is necessary for relational memory as distinct from memory for individual items.