Functional Organziation of the Medial Temporal Lobe

内侧颞叶的功能组织

• 批准号: 8117173
• 负责人: Wendy A. Suzuki
• 金额: $ 33.06万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-08-20 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8117173
• 关键词: Affect; Aging; Alzheimer' s Disease; Animals; Area; Association Learning; Attention Deficit Disorder; Behavioral; Brain; Cells; Complex; Detection; Disease; Episodic memory; Event; Exhibits; Familiarity; Foundations; Goals; Hippocampus (Brain); Impairment; Individual; Learning; Lesion; Literature; Location; Medial; Memory; Memory Disorders; Memory impairment; Monkeys; Motor; Nature; Pattern; Performance; Play; Rattus; Research; Resolution; Rodent; Role; Schizophrenia; Signal Transduction; Stimulus; Structure; Techniques; Temporal Lobe; Testing; Time; Variant; classical conditioning; design; developmental disease; entorhinal cortex; neurophysiology; nonhuman primate; novel; public health relevance; relating to nervous system; research study; theories; therapy development

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.

描述（由申请人提供）：虽然很明显，内侧颞叶（MTL）的结构对于我们学习和重新培训事实，事件和关系的新信息至关重要，但单个MTL结构对学习和记忆的具体贡献仍然不足。该提案的目的是利用非人类灵长类动物中行为神经生理学的精确空间和时间分辨率，以表征各个MTL领域的特定贡献及其对各种MTL依赖性任务的相互作用。在AIM 1中，我们将使用已知对MTL损害敏感的有条件运动关联任务，以使用单个和多个Tetrode记录来表征Intorhinal和parahippocampal Cortices中与任务相关和学习相关的信号。我们将在以前的研究中解释我们的发现，该研究描述了在执行相同的关联学习任务期间，海马和海马和周围皮层中的关联学习信号。使用有条件的电机关联任务的变体，该任务强调编码，需要模式分离或召回，需要完成模式完成，我们将测试以下假设：与面积CA1或Intorhinal Cortex相比，海马的面积可能最强烈或最快地参与编码和回忆版本。在这些实验中进行的单个和多四极管记录将使我们首次表征新的关联学习过程中各个领域以及整个领域的相关活动。在AIM 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，使用偶然的外观任务类似于大鼠使用的偶然空间/上下文编码任务。了解单个MTL结构的功能和功能相互作用对影响记忆的各种疾病状态的治疗具有重要意义，这些状态包括阿尔茨海默氏病，精神分裂症，注意力缺陷障碍以及衰老中存在的记忆障碍。阿尔茨海默氏病，精神分裂症，发育障碍和衰老都涉及与内侧颞叶损害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关键内侧颞叶区域对记忆重要的贡献和相互作用。这些信息将成为影响内侧颞叶的记忆障碍治疗方法的重要基础。