AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

长期目标是获得系统、详细的 了解前脑的组织和传入调节 大鼠的胆碱能投射神经元，特别是在诸如 对角线带和透镜状下的垂直和水平边缘 无名实体。 为了实现这一目标，我们将确定 胆碱能传入神经的来源和化学特性 使用一系列组合的免疫细胞化学和示踪剂投射神经元 光学和电子显微镜水平的技术。 具体 将尝试研究精细突触关节模式 这些传入神经元的胆碱能投射神经元的不同部分 使用最近推出的切片高尔基技术。 我们还建议通过生化方法检查去除 单胺能传入神经对胆碱乙酰转移酶活性的影响 胆碱能投射神经元。 作为这些实验的一部分，我们将 确定胆碱能投射神经元与年龄相关的易感性 传入剥夺。 定量光电子显微镜 还将继续进行局部和外在突触的研究，以便 表征胆碱能投射神经元的突触输入 定量术语（突触/细胞比率、细胞和突触密度）。 这项研究将提供有关组织的重要信息 胆碱能投射系统并将检验功能障碍的假设 或特定传入神经的丧失可能导致萎缩或退化 基底前脑胆碱能神经元。 这些神经元的完整性是 显然是正常认知功能和萎缩所必需的或 可靠地观察到基底前脑胆碱能神经元的变性 阿尔茨海默病。

The long-term goal will be to obtain a systematic and detailed understanding of the organization and afferent regulation of forebrain cholinergic projection neurons of the rat, especially in areas such as the vertical and horizontal limb of the diagonal band and the sublenticular substantia innominata. In order to achieve this goal, we will identify the sources and chemical characteristics of the afferents the cholinergic projection neurons using a series of combined immunocytochemical and tracer techniques at both the light and electron microscope level. Specific attempts will be made to study the fine synaptic articulation pattern of these afferents on different parts of the cholinergic projection neuron using the recently introduced section-Golgi technique. We also propose to examine biochemically the effect of removal of monoaminergic afferents on the activity of choline acetyltransferase in cholinergic projection neurons. As part of these experiments, we will determine the age-related susceptibility of cholinergic projection neurons to afferent deprivation. Quantitative light and electron microscopic studies of local and extrinsic synapses will also proceed in order to characterize the synaptic input to the cholinergic projection neurons in quantitative terms (synapse/cell ration, cell and synaptic densities). This study will provide important information about the organization of the cholinergic projection system and will test the hypothesis that dysfunction or loss of specific afferents might result in atrophy or degeneration of basal forebrain cholinergic neurons. The integrity of these neurons is apparently necessary for normal cognitive function and atrophy or degeneration of basal forebrain cholinergic neurons is reliably observed in Alzheimer's disease.