Functional Organziation of the Medial Temporal Lobe

内侧颞叶的功能组织

• 批准号: 7911769
• 负责人: Wendy A. Suzuki
• 金额: $ 33.43万
• 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/7911769
• 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; Hand; 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; Work; 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）：虽然内侧颞叶（MTL）的结构对于我们学习和重新训练关于事实、事件和关系的新信息的能力至关重要，但对于单个内侧颞叶结构对学习和记忆的具体贡献仍然知之甚少。本研究的目标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区域的具体贡献及其对各种MTL依赖性任务的相互作用。在Aim 1中，我们将使用已知对MTL损伤敏感的条件运动关联学习任务，使用单和多个四极体记录来表征内嗅和海马旁皮层中任务相关和学习相关的信号。我们将在先前的研究背景下解释我们的发现，这些研究描述了在执行相同的联想学习任务时海马体和周围皮层的联想学习信号。使用强调编码（需要模式分离）或回忆（需要模式完成）的条件运动关联任务的变体，我们将测试海马体的CA3区域可能比CA1区域或内嗅皮层更强烈或更快地参与任务的编码和回忆版本。在这些实验中完成的单四极管和多四极管记录将使我们第一次能够在新的联想学习过程中描述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，使用类似于大鼠中使用的附带空间/上下文编码任务的附带查找任务。了解单个MTL结构的功能和功能相互作用对于开发各种影响记忆的疾病状态的治疗方法具有重要意义，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衰老中存在的记忆障碍。阿尔茨海默病、精神分裂症、发育障碍和衰老都涉及与内侧颞叶损伤相关的学习和记忆障碍。在这里，我们建议使用神经生理学记录技术来表征对记忆重要的关键内侧颞叶区域的个体贡献和相互作用。这一信息将成为治疗影响内侧颞叶的记忆障碍的重要基础。