AFFERENT REGULATION OF CHOLINERGIC FOREBRAIN NEURONS

长期目标将是获得系统和详细的 对前脑的组织和传入调节的认识 大鼠的胆碱能投射神经元，特别是在 斜角带和豆状下带的垂直和水平分支 无名质。为了实现这一目标，我们将确定 胆碱能神经传入物质的来源和化学特征 一系列免疫细胞化学和示踪剂联合应用的投射神经元 在光学和电子显微镜水平上的技术。特定的 将尝试研究细微突触的发音模式。 胆碱能投射神经元不同部位的这些传入 使用最近引进的切面-高尔基技术。 我们还建议从生物化学的角度研究去除 单胺能传入对大鼠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 测定胆碱能投射神经元的年龄相关敏感性 传入性剥夺。定量光学和电子显微镜 对局部和外部突触的研究也将继续进行，以便 脑内胆碱能投射神经元的突触输入特征 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说 或特定传入神经元的丧失可能会导致脑萎缩或变性。 基底前脑胆碱能神经元。这些神经元的完整性是 显然对正常的认知功能和萎缩是必要的 基底前脑胆碱能神经元变性是可靠的观察到 阿尔茨海默氏症。

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.