CENTRAL CHOLINERGIC PATHWAYS

新皮层外套膜和边缘前脑结构接受了潜在的 胆碱能神经支配 最近的实验已经证实， 事实上，所有这些神经支配都来自脑内的胆碱能神经元。 基底前脑 这些胆碱能神经元位于隔区， 在斜角带核和Meynert基底核。 我们 我建议准备一个详细的地图集，这些神经元的分布， 猴子和人类。 此外，我们将研究他们的发射器 细胞化学、形态学特化和连接模式。 我们 还将研究这些胆碱能投射的年龄相关变化 神经元 中枢胆碱能通路与人类疾病的相关性 最近成为了人们关注的焦点。 已经显示 阿尔茨海默病患者的大脑皮层 胆碱能神经支配和这种损害可能反映了损害的 基底核 从基底核到基底核的胆碱能通路 皮质套也可能在精神分裂症、亨廷顿病、 和帕金森症 有理由相信， 与年龄相关的认知变化也与以下因素密切相关： 皮质胆碱能神经支配异常。 因此，信息 中枢胆碱能通路的变化可能与广泛的 精神和神经疾病以及认知改变 在生理老化过程中发生的变化。 我们将采用的方法包括：免疫组织化学与 胆碱乙酰转移酶、乙酰胆碱酯酶单克隆抗体 组织化学，辣根过氧化物酶轴突运输，氚化氨基 酸和荧光示踪剂，高尔基技术和2-脱氧葡萄糖 放射自显影

The neocortical mantle and limbic forebrain structures receive susbtantial cholinergic innervation. Recent experiments have established that virtually all of this innervation arises from cholinergic neurons in the basal forebrain. These cholinergic neurons are found in the septal area, in the diagonal band nuclei and in the nucleus basalis of Meynert. We propose to prepare a detailed atlas of the distribution of these neurons in monkeys and in humans. Furthermore, we will study their transmitter cytochemistry, morphological specializations and connectivity patterns. We will also investigate age-related changes in these cholinergic projection neurons. The relevance of central cholinergic pathways to human disease conditions has recently become the focus of great interest. It has been shown that patients with Alzheimer's Disease have a selective impairment of cortical cholinergic innervation and that this impairment may reflect damage to the nucleus basalis. The cholinergic pathways from the nucleus basalis to the cortical mantle may also be abnormal in schizophrenia, Huntington's Disease and in Parkinsonism. There is reason to believe that some of the age-related changes in cognition are also intimately related to abnormalities in the cholinergic innervation of cortex. Thus, information of central cholinergic pathways may be directly relevant to a wide spectrum of mental and neurological diseases as well as to the cognitive alterations that occur in the course of physiological aging. The methods that we will employ include: immunohistochemistry with monoclonal antibodies to choline acetyltransferase, acetylcholinesterase histochemistry, axonal transport of horseradish peroxidase, tritiated amino acids, and fluorescent tracers, Golgi techniques and 2-deoxyglucose autoradiography.