The Neural Basis of Relational Memory

描述(申请人提供)：记忆力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超过2000万美国人。我们的长期目标是帮助更好地了解记忆过程背后的神经机制，以便使我们更接近为这些残疾患者开发新的治疗方法。这项提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元素之间的任意或偶然关系联系在一起的能力。然而，目前几乎没有证据表明灵长类海马区在单个神经元或神经元组的水平上存在关系记忆信号。猴子可以在一些与人类完全相同的关系记忆任务中接受测试，因此，对猴子海马区单个单位和神经元网络活动的神经生理学研究将有助于识别构成关系记忆基础的神经元表征的性质。根据初步数据，我们假设海马区的单个神经元和同步的神经元集合在活动中显示出可能用于关系记忆的调制。这里提出的实验将直接验证这一假设，使用多电极记录的尖峰活动和参与一系列关系记忆任务的猴子海马区的局部场电位(LFP)，改编自人类文献。我们将研究单个单位放电率和棘波-场神经元同步的调制与涵盖各种领域的关系记忆性能，例如，空间、背景和时间。此外，为了评估这些海马电生理关联是否对关系记忆过程至关重要，或者在缺乏功能海马体的情况下，这些过程是否也可以得到内侧颞叶皮质区域的支持，我们将测试海马体限制性损伤对这些关系记忆任务的影响。拟议的实验有以下潜在的结果：1)确定灵长类动物海马区神经元活动的变化，发出关系联系学习的信号，2)确定神经元同步是关系记忆表现的可能机制，以及3)解决人类损伤研究中关于海马体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.