PHYSIOLOGY OF CHOLINERGIC BASAL FOREBRAIN NEURONS

阿尔茨海默氏病和阿尔茨海默氏型老年性痴呆是 病因不明的衰弱性神经系统疾病。 一 大量解剖学和组织化学数据 这表明基底节区的胆碱能神经元 前脑在疾病过程中受损。 可是 对这些细胞的正常生理学知之甚少， 更少的病理生理过程发生。 的缺乏 电生理数据的结果是由于无法清楚地 分离并鉴定胆碱能神经元。 最近，一种方法 为了克服这些困难，开发了一种 细胞内双标记方法， 胆碱能神经元 离体豚鼠脑片 包含基底前脑胆碱能核的制剂 也得到了发展。 神经元将使用 细胞内记录、电压钳和定量 药理学技术 全细胞膜片钳技术 也将被用于研究急性心肌梗死的细胞生理学。 分离的细胞 本提案的总体目标是 研究细胞生理学和药理学， 位于基底节内的胆碱能和非胆碱能神经元 前脑核团 电压依赖性电导，突触 这些神经元的机制和药理学敏感性将 被研究。 假设这些细胞类型明显 不同的细胞特性， 将测试潜在的治疗药物。 定量 关于胆碱能神经元生理学的信息将 成为未来药理学研究和未来 胆碱能病理生理学的细胞模型。 长期目标 是为了研究胆碱能神经的生理/药理学变化， 病理生理条件下的神经元和发展潜力 阿尔茨海默病和老年痴呆症的治疗方法。

Alzheimer's disease and senile dementia of the Alzheimer's type are debilitating neurological disorders with unknown etiologies. A significant quantity of anatomical and histochemical data are available to suggest that cholinergic neurons in the basal forebrain are damaged during the disease process. However, very little is known about the normal physiology of these cells, much less the pathophysiological processes that occur. The paucity of electrophysiological data results from the inability to clearly separate and identify cholinergic nerons. A method has recently been developed to overcome these difficulties using an intracellular double-labelling procedure to specifically identify cholinergic neurons. An in vitro guinea pig brain slice preparation that includes cholinergic nuclei of the basal forebrain has also been developed. Neurons will be studied using intracellular recording, voltage-clamp and quantitative pharmacological techniques. Whole-cell patch-clamping techniques will also be used to study the cellular physiology of acutely dissociated cells. The overall goals of the present proposal are to study the cellular physiology and pharamacology of both cholinergic and noncholinergic neurons located within basal forebrain nuclei. The voltage-dependent conductances, synaptic mechanisms and pharmacological sensitivity of these neurons will be studied. The hypotheses that these cell types are markedly different in terms of cellular properties and in response to potential therapeutic drugs will be tested. Quantitative information concerning the physiology of cholinergic neurons will be a starting point for future pharmacological studies and future cellular models of cholinergic pathophysiology. Long range goals are to study physiological/pharmacological changes in cholinergic neurons under pathophysiological conditons and to develop potential treatments for Alzheimer's disease and senile dementia.