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的 分布的神经元损失，导致各种神经元功能的下降， 认知领域 利用现代体视学方法的最新研究 挑战这一观点，建立坦率的神经元变性， 老龄化在程度上是有限的，在区域上也是有选择性的。 拟议 项目建立在这一基础上的调查结果，以文件的结构 老年海马结构和相关脑区的状态， 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 认知功能的数据。 利用 跨物种神经心理学证据的趋同，平行 神经解剖学研究将在大鼠和非人灵长类动物中进行 模型 该提案涉及为《行动纲领》确定的三个目标， 项目整体规划。 一组调查将利用现代 体视学技术，系统地检查神经元数量， 皮质和皮质下脑系统与年龄相关的认知 下降（方案目标1）。 这些分析将集中在：1） 内嗅和嗅周皮质现在被理解为包括 内侧颞叶记忆系统的关键组成部分，2）定义 基底前脑细胞群显著影响海马和 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。 第二组 实验是基于这样的观察，即衰老是伴随着一个 强大的神经胶质反应，提供了一个潜在的窗口，神经生物学 负责与年龄相关的认知能力下降的机制（计划 目标4）。 这些研究将确定衰老对 星形胶质细胞的数量和大小，特别关注 神经解剖学选择性的那些影响，预测认知 老年人的地位。 研究的最后一个组成部分检查了 海马连接的细微变化是一个更重要的因素， 比弗兰克神经元更显著的正常认知老化特征 退化（程序目标2）。 利用齿状回 作为相对简单的模型系统，图像分析方法将用于 检查神经解剖学上的层状组织， 神经化学定义的海马体输入在衰老过程中发生改变。 总的来说，这些研究代表了朝着 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.