Functional Organziation of the Medial Temporal Lobe

描述(由申请人提供)：尽管内侧颞叶(MTL)的结构显然对我们学习和再训练有关事实、事件和关系的新信息的能力至关重要，但个别MTL结构对学习和记忆的具体贡献仍然知之甚少。这项研究的目的是利用非人类灵长类动物行为神经生理学的精确时空分辨率来表征单个MTL区域的特定贡献及其相互作用对各种MTL依赖任务的影响。在目标1中，我们将使用一个已知对MTL损伤敏感的条件运动联想学习任务，使用单个和多个四极管记录来表征内嗅觉和海马旁皮质中与任务相关和学习相关的信号。我们将在之前的研究中解释我们的发现，该研究描述了在执行相同的联想学习任务时，海马区和周围皮质中的联想学习信号。使用强调编码、需要模式分离或回忆、需要模式完成的条件性运动联想任务的变体，我们将检验这样一个假设，即与CA1区或内嗅皮层相比，海马区CA3可能最强烈或最快地参与任务的编码和回忆版本。在整个实验过程中进行的单四极管和多四极管记录将使我们第一次能够表征在新的联想学习过程中单个区域内以及跨区域的相关活动。在目标2中，我们还将使用模式完成和模式分离的计算来区分单个MTL区域的功能，使用类似于RAT中使用的附带空间/上下文编码任务的附带看任务。了解单个MTL结构的功能和功能相互作用对于开发治疗各种影响记忆的疾病状态具有重要意义，这些疾病包括阿尔茨海默病、精神分裂症、注意力缺陷障碍以及随着年龄增长而出现的记忆障碍。阿尔茨海默氏症、精神分裂症、发育障碍和衰老都涉及与内侧颞叶受损相关的学习和记忆障碍。在这里，我们建议使用神经生理记录技术来表征个体对记忆重要的内侧颞叶区域的贡献和相互作用。这些信息将成为开发影响内侧颞叶的记忆障碍治疗方法的重要基础。

DESCRIPTION (provided by applicant): While it is clear that the structures of the medial temporal lobe (MTL) are essential for our ability to learn and retrain new information for facts, events and relationships, the specific contributions of individual MTL structures to learning and memory remain poorly understood. The goal of this proposal is to take advantage of the precise spatial and temporal resolution of behavioral neurophysiology in the non-human primate to characterize the specific contributions of individual MTL areas and their interactions to various MTL-dependent tasks. In Aim 1, we will use a conditional motor association learning task known to be sensitive to MTL damage, to characterize the task-related and learning related signals in both the entorhinal and parahippocampal cortices using single and multiple tetrode recordings. We will interpret our findings in the context of our previous studies describing the associative learning signals in both in the hippocampus and perirhinal cortex during performance of the same associative learning task. Using variants of the conditional motor association task that emphasize either encoding, requiring pattern separation or recall, requiring pattern completion, we will test the hypothesis that area CA3 of the hippocampus may be most strongly or most quickly engaged in both encoding and recall versions of the task compared to area CA1 or the entorhinal cortex. Single and multi-tetrode recordings done throughout these experiments will allow us for the first time to characterize the correlated activity both within individual areas as well as across areas during new associative learning. In Aim 2 we will also use the computations of pattern completion and pattern separation to differentiate the functions of individual MTL areas using an incidental looking task analogous to incidental spatial/contextual encoding tasks used in rats. Understanding the functions and functional interactions of individual MTL structures has important implications for the development of treatments for the wide variety of disease states that affect memory including Alzheimer's disease, schizophrenia, attention deficit disorder as well as the memory impairments present in aging. Alzheimer's disease, schizophrenia, developmental disorders and aging all involve impairments in learning and memory associated with damage to the medial temporal lobe. Here we propose to use neurophysiological recording techniques to characterize the individual contributions and interactions of the key medial temporal lobe areas important for memory. This information will serve as an important foundation for the development of treatments for disorders of memory that affect the medial temporal lobe.