NEUROANATOMICAL STUDIES OF THE AGED HIPPOCAMPAL FORMATION

人们普遍认为，正常衰老会导致中度和弥漫性衰老 分布式神经元丢失，有助于多种疾病的下降 认知域。现代体视学方法的最新研究 挑战这一观点，建立了坦率的神经元变性 老龄化在规模上是有限的，在地区上也是有选择性的。建议数 项目建立在调查结果的基础上，以记录结构 老年海马体结构及相关脑区的研究现状 支持正常的学习和记忆。实验的统一主题 定量形态测量结果将在上下文中评估 相同受试者的认知功能数据。利用一种 跨物种的神经心理学证据的趋同，平行 神经解剖学研究将在一种非人类灵长类动物大鼠身上进行 模特们。该提案涉及为 计划项目作为一个整体。一组调查将利用现代 体视学技术系统地检测脑内神经元数量 与年龄相关认知有关的皮质和皮质下大脑系统 拒绝(计划目标1)。这些分析将集中在：1) 内嗅皮层和周边皮质，现在被理解为包括 内侧颞叶记忆系统的关键组件，2)定义 显著影响海马区和脑区的基底前脑细胞群 皮质功能，以及3)前额叶皮质的细分 支持对衰老敏感的认知过程。第二套 实验是基于这样一种观察，即衰老伴随着 强大的神经胶质反应，为研究神经生物学提供了一个潜在的窗口 年龄相关性认知功能减退的机制(方案 目标4)。这些调查将确定老龄化对健康的影响 星形胶质细胞的数量和大小，特别是关注 预测认知功能的影响的神经解剖学选择性 老年人的状况。这项研究的最后一个组成部分是 海马区连接性的细微变化是一种更 正常认知老化的显著特征比坦率的神经元 退化(方案目标2)。利用齿状回 作为相对简单的模型系统，将采用图像分析的方法 检查神经解剖学和神经纤维板的组织结构 海马体的神经化学定义的输入在衰老过程中会发生变化。 综上所述，这些研究代表着朝着 建立认知老化的定量神经解剖学。

Normal aging is widely assumed to result in moderate and diffusely distributed neuron loss that contributes to decline across a variety of cognitive domains. Recent studies using modern stereological methods challenge this view, establishing that frank neuronal degeneration in aging is both limited in magnitude and regionally selective. The proposed project builds on this foundation of findings to document the structural status of the aged hippocampal formation and related brain regions that support normal learning and memory. A unifying theme of the experiments is that quantitative morphometric results will be evaluated in the context of data on cognitive function the same subjects. Capitalizing on a convergence of neuropsychological evidence across species, parallel neuronanatomical studies will be conducted in rat an nonhuman primate models. The proposal addresses three of the objectives identified for the Program Project as a whole. One set of investigations will utilize modern stereological techniques to systematically examine neuron number in cortical and subcortical brain systems implicated in age-related cognitive decline (Program Objective 1). These analyses will focus on: 1) the entorhinal and perirhinal cortices that are now understood to comprise critical components of the medial temporal lobe memory system, 2) defined basal forebrain cell groups that prominently influence hippocampal and cortical function, and 3) subdivisions of the prefrontal cortex that support cognitive processes sensitive to aging. A second set of experiments is based on the observation that aging is accompanied by a robust glial response, providing a potential window on the neurobiological mechanisms responsible for age-related cognitive decline (Program Objective 4). These investigations will define the effects of aging on the number and size of astrocytes, focusing especially on the neuroanatomical selectivity of those effects that predict the cognitive status of aged individuals. A final component of the research examines the proposal that subtle changes in hippocampal connectivity are a more prominent signature of normal cognitive aging than frank neuronal degeneration (Program Objective 2). Taking advantage of the dentate gyrus as relatively simple model system, image analysis methods will be used to examine whether the laminar organization of neuroanatomically and neurochemically defined inputs to the hippocampus is altered during aging. Taken together, the studies represent an important step toward establishing a quantitative neuroanatomy of cognitive aging.