COGNITIVE FUNCTION IN AGED MONKEY

该项目的总体目标是建立一个 非人灵长类动物模型，用于定义 与年龄相关的认知能力下降 目的大样本年轻人（n = 20)将在整个程序中对老年（n = 40）恒河猴进行试验 专门用来检验记忆处理能力的 1)一种非人灵长类动物的配对联想学习，2）一种 传递性推理程序测量学习和记忆， 层次关系，以及3）迷宫导航任务，强调 学习和记忆复杂的空间关系。 为了 记录这些评估的选择性和敏感性， 还将根据几项标准学习和 记忆程序 结果这些研究提供了第一个 老年人陈述性记忆功能的系统分析 非人灵长类动物，建立适当的证据框架 将我们的行为观察与选定的荷尔蒙和 衰老的神经生物学特征 尿雌激素水平 与延迟反应味觉的表现受损有关。 未来的方向实验将开始测试的潜力 激素替代对年龄相关学习的保护作用， 记忆受损 结合免疫组织化学和 定量共聚焦激光显微镜也提出来确定 陈述性记忆障碍是否与 最近在老年猴中记录的NMDA受体丢失 海马体。 这些研究将检验雌激素 缺乏通过影响海马神经元影响认知老化 谷氨酸受体介导学习相关的细胞可塑性。 预计拟议的研究将大大推进进展 来定义认知、内分泌和 灵长类的神经生物学衰老 关键词记忆，衰老，学习， 雌激素缺乏症基金NIH Grant AG 10606 Publications Rapp，P.R. （1998）老年海马体中的代表性组织。 Hippocampus，8，432-435. Rapp，P.R. 03 The Fantasy（1998） 在正常认知老化的研究中。 定量神经解剖学 一张图片胜过千言万语，一个数字胜过千言万语 图片. J.莫里森和P.霍夫（编辑），华盛顿，华盛顿特区 Neuroscience，pp. 56-65.

Significance The overall goals of this project are to establish a non-human primate model for defining the neurobiological basis of age-related cognitive decline. Objectives Large samples of young (n = 20) and aged (n = 40) rhesus monkeys will be tested across procedures specifically designed to examine these mnemonic processing capacities 1) a nonhuman primate analog of paired associate learning, 2) a transitive inference procedure measuring learning and memory for hierarchical relationships, and 3) a maze navigation task emphasizing learning and memory for complex spatial relationships. In order to document the selectivity and sensitivity of these assessments, performance will also be evaluated on several standard learning and memory procedures. Results These studies are providing the first systematic analysis of declarative memory function in the aged nonhuman primate, establishing an appropriate framework of evidence for relating our behavioral observations to selected hormonal and neurobiological signatures of aging. Urinary estrogen levels have been associated with impaired performance on delayed response tastes. Future Directions Experiments will be initiated to test the potential protective effects of hormone replacement on age-related learning and memory impairment. Studies combining immunohistochemistry and quantitative confocal laser microscopy are also proposed to determine whether declarative memory impairment is linked to the substantial loss of NMDA receptors recently documented in the aged monkey hippocampus. These studies will test the hypothesis that estrogen deficiency influences cognitive aging through effects on hippocampal glutamate receptors that mediate learning-related cellular plasticity. The proposed research is expected to substantially advance progress toward defining the interactions between cognitive, endocrine and neurobiological aging in primates. KEY WORDS memory, aging, learning, estrogen deficiency FUNDING NIH Grant AG10606 PUBLICATIONS Rapp, P.R. (1998) Representational organization in the aged hippocampus. Hippocampus, 8, 432-435. Rapp, P.R. (1998) Quantitative morphometry in the study of normal cognitive aging. In Quantitative Neuroanatomy A Picture is Worth a Thousand Words, but a Number is Worth a Thousand Pictures. J. Morrison and P. Hof (eds.), Washington, D.C. Society for Neuroscience, pp. 56-65.