HIPPOCAMPAL PLASTICITY AND ACUTE ETHANOL

此应用程序的总体目标是确定 海马体的特定皮层下输入可能在介导 酒精对这个结构的急性中毒作用， 已知对乙醇的神经药理学高度敏感。 这些 体内研究将补充更普遍的体外研究 电生理学研究乙醇作用于 海马体。 此外，这些调查将提供新的信息， 关于乙醇对细胞外调节输入的作用， 海马，仅在完整的制备物中可观察到。 我们提出的 研究旨在验证三个主要假设：1） 海马表现出区域和细胞特异性的急性敏感性 酒精中毒水平; 2）皮层下输入到 海马选择性地影响乙醇对复发性 齿状回的抑制和可塑性; 3）多巴胺， 起源于腹侧被盖神经元投射部位，功能 作为神经药理学作用中的关键神经递质， 乙醇对海马体的影响 我们将采用电生理分析 急性局部和全身乙醇对海马单个神经元的影响， 单位活动和突触诱发事件在体内麻醉 大鼠 我们将研究原位微电泳 乙醇在内侧隔和腹侧被盖区，皮质下 结构与相关的输入到海马，对复发性 抑制和乙醇对内侧隔和腹侧被盖区的影响 条件反射的传入诱发反应的三个子区域的 海马，并将确定乙醇与主要的相互作用， 这些途径的神经递质：乙酰胆碱，GABA和多巴胺。 我们假设这种体内海马模型提供了一种独特的 有机会分析乙醇对区域和地方的作用 电路和它们的神经化学底物与认知 和乙醇的增强性能。

The overall objective of this application is to determine the role specific subcortical inputs to the hippocampus may have in mediating the acute intoxicating actions of ethanol on this structure, a brain region known to be highly sensitive to the neuropharmacology of ethanol. These in vivo studies will complement the more prevalent in vitro electrophysiological investigations of ethanol actions on the hippocampus. Moreover, these investigation will provide new information regarding ethanol actions on extrinsic modulatory inputs to the hippocampus, only observable in the intact preparation. Our proposed studies are designed to test three major hypotheses: 1) That the hippocampus exhibits regional and cell specific sensitivity to acute intoxicating levels of ethanol; 2) The subcortical inputs to the hippocampus selectively influence the actions of ethanol on recurrent inhibition and plasticity in the dentate gyrus; and 3) That dopamine, originating from ventral tegmental neuronal projection sites, functions as a critical neurotransmitter in the neuropharmacological actions of ethanol on the hippocampus. We will employ electrophysiological analysis of the effects of acute local and systemic ethanol on hippocampal single- unit activity and synaptically-evoked events in the in vivo anesthetized rat. We will investigate the effects of in situ microelectrophoretic ethanol in the medial septum and ventral tegmental area, subcortical structures with relevant input to the hippocampus, on recurrent inhibition and ethanol on medial septum and ventral tegmental area conditioning of afferent-evoked responses in the three sub-regions of the hippocampus and will determine the interaction of ethanol with the major neurotransmitter of these pathways: acetylcholine, GABA and dopamine. We hypothesize that this in vivo hippocampal model provides a unique opportunity to analyze the actions of ethanol on regional and local circuitry and their neurochemical substrates implicated in the cognitive and reinforcing properties of ethanol.