LOCAL ETHANOL ACTIONS ON CNS NEURONS IN BEHAVING ANIMALS

这是一个香农奖提供部分支持的研究 项目不属于指定机构的资助范围，但 在优秀的边缘。香农奖旨在提供 支持测试方法的可行性;支持进一步测试 和完善研究技术;进行二次分析或提供 数据集;或进行可以证明PI的离散项目 研究能力或为已经优秀的 应用程序.以下摘要摘自原始文件 由主要经销商提交。 描述：本项目的长期目标是阐明 一些细胞和分子机制的潜在急性 酒精调节认知缺陷的作用。 这是一 这是一项复杂的任务，因为它需要使用行为动物， 与此同时，对乙醇行动的监测， 大脑中认知系统的神经元。 此外，由于细胞 乙醇的作用是局部药物作用于细胞的净结果 自身和远程药物作用于其他突触连接的大脑 区域，局部和全身给予乙醇的影响 应该进行检查和比较。 这样的实验是无法进行的 用传统的神经科学方法 相反，本项目 提出了一种新的研究策略，具体如下： 首先，该项目将利用最近开发的方法， 单细胞记录和脑内微透析技术在自由活动中的应用 大鼠 第二，该项目将重点放在海马的检查上， 位置细胞，它们显然是大脑认知系统的一部分。 根据初步研究，该项目的中心假设是 当乙醇作用于中枢神经系统时， 放置单元格，主要是通过对单元格本身的局部操作。 到 为了检验这一假设，将追求三个具体目标。 在具体目标1中，研究了乙醇对燃烧的局部作用。 将在大鼠中测定海马定位细胞和中间神经元 执行空间导航。 乙醇将通过以下方式在当地使用： 海马内微透析，以及海马内细胞的放电。 将检查透析区域。 在具体目标2中， 全身（腹膜内）给予乙醇， 将在大鼠中测定海马定位细胞和中间神经元 执行空间导航。 在具体目标3中，海马 乙醇浓度后，其局部应用与 将确定微透析及其全身给药。 这 神经化学研究将确保特定目标中生成的数据 1和2将进行比较和适当的解释。

THIS IS A SHANNON AWARD PROVIDING PARTIAL SUPPORT FOR THE RESEARCH PROJECTS THAT FALL SHORT OF THE ASSIGNED INSTITUTE'S FUNDING RANGE BUT ARE IN THE MARGIN OF EXCELLENCE. THE SHANNON AWARD IS INTENDED TO PROVIDE SUPPORT TO TEST THE FEASIBILITY OF THE APPROACH; DEVELOP FURTHER TESTS AND REFINE RESEARCH TECHNIQUES; PERFORM SECONDARY ANALYSIS OR AVAILABLE DATA SETS; OR CONDUCT DISCRETE PROJECTS THAT CAN DEMONSTRATE THE PI'S RESEARCH CAPABILITIES OR LEND ADDITIONAL WEIGHT TO AN ALREADY MERITORIOUS APPLICATION. THE ABSTRACT BELOW IS TAKEN FROM THE ORIGINAL DOCUMENT SUBMITTED BY THE PRINCIPAL INVESTIGATOR. DESCRIPTION: The long-term objective of this project is to elucidate some of the cellular and molecular mechanisms underlying the acute actions of alcohol that mediate cognitive deficits. This is a complicated task, because it requires the use of behaving animals and at the same time the monitoring of ethanol actions specifically on the neurons of the cognitive system in brain. Moreover, since the cellular effects of ethanol are the net results of local drug actions on the cells themselves and remote drug actions on other, synaptically connected brain areas, the effects of both locally and systemically administered ethanol should be examined and compared. Such experiments cannot be conducted with traditional neuroscience methods. Instead, the present project offers a novel research strategy, which is as follows: First, the project will utilize the recently developed method of combined single cell recording and intracerebral microdialysis in freely behaving rats. Second, the project will focus on the examination of hippocampal place cells, which are clearly parts of the cognitive system in brain. Based on preliminary studies, the central hypothesis of this project is that when ethanol acts in CNS, it impairs the firing of hippocampal place cells, principally via local actions on the cells themselves. To test this hypothesis, three specific aims will be pursued. In Specific Aim 1, the local actions of ethanol on the firing of hippocampal place cells and interneurons will be determined in rats performing spatial navigation. Ethanol will be applied locally via intrahippocampal microdialysis, and the firing of the cells within the dialysis area will be examined. In Specific Aim 2, the effects of systemic (intraperitoneal) administration of ethanol on the firing of hippocampal place cells and interneurons will be determined in rats performing spatial navigation. In Specific Aim 3, the hippocampal concentrations of ethanol after both its local applications with microdialysis and its systemic administrations will be determined. This neurochemical study will assure that the data generated in Specific Aims 1 and 2 will be compared and interpreted appropriately.