HIPPOCAMPAL PLASTICITY AND ACUTE ETHANOL

此应用程序的总体目标是确定角色 海马区的特定皮质下输入可能在介导 酒精对这一结构的急性醉酒作用，这是大脑的一个区域 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 乙醇作用于大鼠脑内的电生理研究 海马体。此外，这些调查将提供新的信息 关于乙醇对外在调制输入的作用 海马体，只有在完整的准备中才能观察到。我们的建议 研究旨在检验三个主要假设：1) 海马区表现出局部和细胞特异性对急性脑缺血的敏感性 令人陶醉的酒精水平；2)皮层下对 海马区选择性地影响乙醇对复发的作用 齿状回的抑制和可塑性；3)多巴胺， 起源于腹侧被盖神经元的投射部位、功能 作为神经递质在神经药理作用中的作用 海马体上的乙醇。我们将使用电生理分析 急性局部和全身乙醇对大鼠海马神经元的影响 在体麻醉状态下的单位活动和突触诱发事件 老鼠。我们将研究原位微电泳法的效果。 皮质下内侧隔和腹侧被盖区的乙醇 有相关输入到海马体的结构，关于复发 乙醇和乙醇对内侧隔和腹侧被盖区的抑制作用 中枢三个亚区传入诱发反应的条件性研究 并将确定乙醇与主要脑组织的相互作用 这些通路的神经递质：乙酰胆碱、GABA和多巴胺。 我们假设这种活体海马区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 与认知有关的回路及其神经化学底物 以及乙醇的增强性能。

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.