IN VIVO ELECTROPHYSIOLOGY OF ETHANOL-NMDA INTERACTIONS

这项提案的目的是调查 乙醇对N-甲基-D-天冬氨酸诱发的体内神经元活动的影响。这 Proposal在我们实验室进行了最近的活体研究，表明 在广泛的行为相关剂量范围内，乙醇会抑制 N-甲基-D-天冬氨酸(NMDA)的兴奋作用 内侧隔区的神经元。这一发现表明，两者都存在 乙醇敏感和乙醇不敏感NMDA激活的神经元 内侧隔。这项提议将检验假设的含义，即 同时存在乙醇敏感和乙醇不敏感的NMDA激活 通过研究1)乙醇是否特异性地抑制大脑中的神经元 NMDA受体激动剂引起的内侧隔神经元活动 谷氨酸受体的亚型，或者，如果不是，是否在 海人酸激动剂和海人酸激动剂激活的神经元对乙醇敏感 合格谷氨酸受体亚型，2)乙醇中是否存在差异 NMDA激活的内侧隔区神经元的敏感性是由于局部 神经回路的效应或效应，以及3)酒精敏感和 酒精不敏感的NMDA激活神经元存在于特定的大脑部位 除内侧隔外，如果是，神经元所占比例 根据NMDA的不同，这些部位对乙醇的敏感度会有系统地变化 受体亚群分布。第三种方法允许测试 假设乙醇不能抑制对细胞的反应 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.