PHYSIOLOGY OF CHOLINERGIC BASAL FOREBRAIN NEURONS

胆碱能基底前脑神经元的生理学

• 批准号: 3119144
• 负责人: WILLIAM H GRIFFITH
• 金额: $ 6.31万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-01-01 至 1992-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3119144
• 关键词: Alzheimer's disease; electrophysiology; guinea pigs; muscarinic receptor; neurons; neuropharmacology; neurophysiology; parasympathetic nervous system; prosencephalon; synapses; voltage /patch clamp

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.

阿尔茨海默氏病和阿尔茨海默氏型老年痴呆症是 病因不明的使人衰弱的神经系统疾病。 一个 大量的解剖和组织化学数据 可以表明基底核中的胆碱能神经元 前脑在疾病过程中受损。 然而，非常 人们对这些细胞的正常生理机能知之甚少 较少发生的病理生理过程。 的匮乏 电生理数据是由于无法清楚地 分离并鉴定胆碱能神经元。 最近有一个方法 被开发来克服这些困难，使用 细胞内双标记程序可特异性识别 胆碱能神经元。 体外豚鼠脑切片 包括基底前脑胆碱能核的制剂 也已被开发出来。 将使用以下方法研究神经元 细胞内记录、电压钳和定量 药理学技术。 全细胞膜片钳技术 还将用于研究急性细胞生理学 解离的细胞。 本提案的总体目标是 研究两者的细胞生理学和药理学 胆碱能和非胆碱能神经元位于基底层 前脑核。 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。 假设这些细胞类型显着 细胞特性和响应方面不同 将测试潜在的治疗药物。 定量 有关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的起点 胆碱能病理生理学的细胞模型。 长期目标 研究胆碱能的生理/药理学变化 神经元在病理生理条件下并发展潜力 治疗阿尔茨海默病和老年痴呆症。