PHYSIOLOGY AND PHARMACOLOGY OF CHOLINERGIC AND GABAERGIC BASAL FOREBRANE NEURONS

这项研究的长期目标是了解 胆碱能前脑基底核团在正常行为和某些情况下的分布 老年痴呆症和阿尔茨海默病等疾病。在……里面 特别是，胆碱能神经元和GABA能神经元的作用 组成感兴趣的内侧隔/斜角带(MS/DB)核 因为他们参与了一些现象，比如控制 海马节律性慢活动(theta节律)与空间 学习。 人们对其基本生理学和药理学知之甚少。 基底前脑神经元。电生理学的最新发现 表达胆碱乙酰转移酶的MS/DB神经元的特性 为更详细的胆碱能药理研究开辟了道路 神经元。GABA能MS/DB神经元的特征仍有待进一步研究 就这样吧。这项提议的重点是使用体外前脑 结合细胞内记录的切片制备 记录神经元的技术和双重标记以确定基本的 GABA能MS/DB神经元的膜生理学及其开始探索 胆碱能和推测的GABA能MS/DB神经元的药理学。 更具体地说，将讨论以下问题： 1.GABA能的主动膜和被动膜特性是什么 MS/DB神经元？这些神经元将通过细胞内注射进行标记 生物细胞素结合核探针或cDNAs的原位杂交 GAD基因的探针。 2.去极化背后的离子机制是什么 神经降压素和去甲肾上腺素对胆碱能MS/DB神经元的影响 如初步数据所示？神经降压素的哪些亚型和 去甲肾上腺素受体参与了吗？ 3.神经生长因子对成熟胆碱能MS/DB有明显的去极化作用吗 神经元，如已报道的胚胎胆碱能神经元？如果是的话， 涉及哪些受体亚型？ 这些问题将围绕一个共同的主题进行探讨， 神经节律、膜振荡及其机制的研究。 由于MS/DB区是大脑皮层的起搏中心之一 节奏性活动涉及学习、记忆和认知，我们将 关注节律性起搏器和 GABA能和胆碱能神经元的爆发式放电行为。

The long range goal of this research is to understand the role of cholinergic basal forebrain nuclei in normal behavior and in certain diseases such as senile dementia and Alzheimer's disease. In particular, the roles of cholinergic and GABAergic neurons which compose the medial septal/diagonal band (MS/DB) nuclei are of interest because of their involvement in such phenomena as the control of hippocampal rhythmic slow activity (theta rhythms) and spatial learning. Very little is known about the basic physiology and pharmacology of basal forebrain neurons. Recent findings on the electrophysiological properties of MS/DB neurons which express choline acetyltransferase has opened the way for more detailed pharmacological studies on cholinergic neurons. The characterization of GABAergic MS/DB neurons is still to be done. The focus of this proposal is to use the in vitro forebrain slice preparation in combination with intracellular recording techniques and double labeling of recorded neurons to define the basic membrane physiology of GABAergic MS/DB neurons and to begin to explore the pharmacology of cholinergic and presumed GABAergic MS/DB neurons. More specifically, the following questions will be addressed: 1. What are the active and passive membrane properties of GABAergic MS/DB neurons? These neurons will be labeled by intracellular injection of biocytin followed by in situ hybridization of riboprobes or cDNA probes to GAD mRNA. 2. What are the ionic mechanisms which underlie the depolarizing effects of neurotensin and norepinephrine on cholinergic MS/DB neurons, as demonstrated in preliminary data? What subtypes of neurotensin and norepinephrine receptors are involved? 3. Does nerve growth factor acutely depolarize mature cholinergic MS/DB neurons as has been reported for embryonic cholinergic neurons? If so, what receptor subtypes are involved? These questions will be pursued with an attention to a common theme, that of neuronal rhythms, membrane oscillations and their mechanisms. Since the MS/DB region is one of the pacemaker centers for cortical rhythmic activities involved in learning, memory and cognition, we will focus on membrane properties which underlie rhythmic pacemaker and burst firing behavior in GABAergic and cholinergic neurons.