AGED-RELATED CHANGES IN THE LIMBIC SYSTEM OF THE PRIMATE BRAIN

本项目是对以前提交的项目3的修改 其重点是与年龄相关的形态学和神经化学变化， 灵长类动物基底前脑和颞叶边缘系统的状态 个脑袋 目前的项目已经扩大， 化学神经解剖技术来解决细胞中与年龄相关的变化 高亲和力摄取位点的数量、传入神经支配和密度 以及所有主要神经化学物质的突触前和突触后受体 神经支配，而不是细胞损失形式的结构和化学 与年龄相关的认知衰退的底物，包括记忆障碍。 将通过解决以下具体问题来研究这一假设 关于颞叶边缘系统年龄相关变化的目的：（1） 以确定是否存在细胞内在或程度的选择性损失， 死亡或萎缩，（2）确定是否存在选择性损失 内源性或外源性GABA能神经元，（3）以确定是否有 （4）确定是否有损失或 突触形态改变，（5）确定是否有改变 高亲和力神经递质摄取的密度和分布 （6）确定密度是否有变化， 突触前和突触后受体的分布，（7）以确定是否 大细胞神经元丢失的时间过程和特点 基底前脑 此外，与项目2和项目3合作， 另一个目标是确定与年龄有关的密度变化， 高亲和力摄取位点和突触前和突触后的分布 背外侧前额叶联合皮层的受体， 与项目5合作，以确定这些相同的变化 神经递质水平 为了实现这些具体目标， 光学和电子显微镜的测量和最先进的体外 将使用配体结合技术。 这样，在同一个 动物与年龄相关的结构和化学神经解剖学变化， 发生在基底前脑和颞叶边缘系统， 与记忆障碍和其他认知功能障碍有关。

This project is a modification of Project 3 from the previous submission which focuses on age-related changes in the morphological and neurochemical state of the basal forebrain and temporal lobe limbic system of the primate brain. The present project has been expanded to include additional chemical neuroanatomical techniques to address age-related changes in cell number, afferent innervation and, density of high affinity uptakes sites and pre- and postsynaptic receptors of all of the major neurochemical innervation rather than cell loss form the structural and chemical substrates of age-related cognitive decline including memory impairment. This hypothesis will be investigated by addressing the following specific aims concerning age-related changes in the temporal lobe limbic system: (1) to determine if there is a selective loss in intrinsic or extent of cell death or shrinkage, (2) to determine if there is a selective loss in intrinsic or extrinsic GABAergic neurons, (3) to determine if there are alterations in the neuropil, (4) to determine whether there is a loss or altered morphology of synapses, (5) to determine if there are alterations in the density and distribution of high affinity neurotransmitter uptake sites, (6) to determine whether there are alterations in the density and distribution of pre- and postsynaptic receptors, (7) to determine whether the time course and features of the loss of magnocellular neurons of the basal forebrain. Furthermore, in collaboration with Projects 2 and 3, another aim will be to determine the age-related changes in the density and distribution of high affinity uptake sites and pre- and postsynaptic receptors in the dorsolateral prefrontal association cortex, and in collaboration with Project 5, to determine changes in these same neurotransmitter levels. To accomplish these specific aims, a combination of light and electronmicroscopic measures and state-of-the-art in vitro ligand binding techniques will be utilized. In this way, within the same animal the age-related structural and chemical neuroanatomical changes that occur in the basal forebrain and temporal lobe limbic system can be correlated with memory impairments and other cognitive dysfunctions.