IN VIVO ELECTROPHYSIOLOGY OF ETHANOL-NMDA INTERACTIONS

本提案的目的是研究 乙醇对体内N-甲基-D-天冬氨酸诱发的神经元活性的影响。 这 该提案在我们的实验室进行了最近的体内研究， 乙醇，在广泛的行为相关剂量范围内， N-甲基-D-天冬氨酸（NMDA）的兴奋作用，仅在一个子集， 内侧隔的神经元 这一发现表明， 脑中乙醇敏感和乙醇不敏感的NMDA激活神经元 内侧隔 这一提议将检验以下假设的含义： 存在乙醇敏感和乙醇不敏感的NMDA激活 通过研究1）乙醇是否特异性抑制 NMDA受体激动剂诱发的内侧隔神经元活动 谷氨酸受体的亚型，或者，如果不是， 乙醇敏感性发生在由红藻氨酸激动剂激活的神经元中， 使君子酸谷氨酸受体亚型，2）是否差异乙醇 NMDA激活的内侧隔神经元的敏感性是由于局部 影响或神经回路的影响，以及3）是否乙醇敏感， 乙醇不敏感的NMDA激活的神经元存在于选定的脑部位 如果是的话，神经元的比例 对乙醇的敏感性在这些部位系统地变化，这取决于NMDA 受体亚群分布 第三种方法允许测试 的假设，即缺乏抑制乙醇的反应， 一些内侧隔神经元中的NMDA是由于存在两种类型的 NMDA受体，一个对乙醇敏感，另一个对乙醇不敏感。

The goal of this proposal is to investigate the inhibitory effects of ethanol on N-methyl-D-aspartate-evoked neuronal activity in vivo. This proposal pursues recent in vivo studies in our laboratory showing that ethanol, throughout a wide range of behaviorally relevant doses, inhibits the excitatory effects of N-methyl-D-aspartate (NMDA) in only a subset of neurons in the medial septum. This finding indicates that there exist both ethanol-sensitive and ethanol-insensitive NMDA-activated neurons in the medial septum. This proposal will test implications of the hypothesis that there exist both ethanol-sensitive and ethanol-insensitive NMDA activated neurons in brain by investigating 1) whether ethanol specifically inhibits medial septa] neuronal activity evoked by agonists of the NMDA receptor subtype of the glutamate receptor or, if not, whether differences in ethanol sensitivity occur in neurons activated by agonists of kainate and quisqualate glutamate receptor subtypes, 2) whether differences in ethanol sensitivity of NMDA-activated medial septa] neurons are due to local effects or effects of neural circuits, and 3) whether ethanol-sensitive and ethanol-insensitive NMDA-activated neurons exist at selected brain sites other than the medial septum and, if so, whether the proportion of neurons sensitive to ethanol varies systematically at these sites depending on NMDA receptor subpopulation distributions. This third approach permits testing of the hypothesis that the lack of inhibition by ethanol of responses to NMDA in some medial septal neurons is due to the presence of two types of NMDA receptors, one ethanol-sensitive, the other ethanol-insensitive.