PHYSIOLOGY AND PHARMACOLOGY OF CHOLINERGIC AND GABAERGIC BASAL FOREBRANE NEURONS

这项研究的长期目标是了解 胆碱能基底前脑核在正常行为和某些 老年痴呆症、阿尔茨海默病等疾病。 在 特别是，胆碱能和GABA能神经元的作用， 构成内侧隔/斜角带（MS/DB）核团的细胞核是感兴趣的 因为他们参与了诸如控制 海马节律性慢活动（θ节律）和空间 学习 对它的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神经元的性质具有 为更详细的胆碱能药物药理学研究开辟了道路 神经元GABA能MS/DB神经元的特征仍有待进一步研究。 就这么定了这项提案的重点是利用体外前脑 与细胞内记录相结合切片制备 技术和双标记记录的神经元，以确定基本的 GABA能MS/DB神经元的膜生理学，并开始探索 胆碱能和推测的GABA能MS/DB神经元的药理学。 具体而言，将讨论以下问题： 1. GABA能的主动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 随后进行核糖核酸探针或cDNA的原位杂交 GAD mRNA的探针。 2.去极化的离子机制是什么 神经降压素和去甲肾上腺素对胆碱能MS/DB神经元的作用， 初步数据显示，？什么样的神经降压素亚型和 与去甲肾上腺素受体有关吗 3.神经生长因子急性去分化成熟胆碱能MS/DB 胚胎胆碱能神经元的研究如果是这样的话， 涉及哪些受体亚型？ 这些问题将在关注一个共同主题的情况下加以探讨， 神经元节律、膜振荡及其机制。 由于MS/DB区是皮层起搏中心之一， 节奏活动参与学习，记忆和认知，我们将 专注于作为节律性起搏器基础的膜特性， GABA能和胆碱能神经元的爆发放电行为。

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.