LOCAL ETHANOL ACTIONS ON CNS NEURONS IN BEHAVING ANIMALS

这是香农奖，为这项研究提供部分支持 项目低于指定研究所的资助范围，但 都在最优秀的边缘。香农奖旨在提供 支持测试该方法的可行性；开发进一步的测试 并改进研究方法；进行二次分析或可用 数据集；或执行可演示PI的离散项目 研究能力或为已经功成名就的 申请。下面的摘要摘自原始文件 由首席调查员提交。 描述：这个项目的长期目标是阐明 急性心肌梗死的一些细胞和分子机制 酒精对认知缺陷的调节作用。这是一个 复杂的任务，因为它需要使用表现良好的动物和 同时，对乙醇行动的监测特别是对 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。 自己和远程药物对其他突触连接的大脑的作用 地区，当地和全身注射乙醇的影响 应该进行检查和比较。这样的实验不能进行 用传统的神经科学方法。相反，目前的项目 提供了一种新颖的研究策略，具体如下： 首先，该项目将利用最近开发的组合方法 自由活动中的单细胞记录和脑内微透析 老鼠。第二，该项目将重点放在海马区的检查上 放置细胞，这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 当酒精作用于中枢神经系统时，它会损害海马区的放电 放置单元格，主要是通过对单元格本身的本地操作。至 检验这一假设，将追求三个具体目标。 在特定目标1中，乙醇在燃烧过程中的局部作用 大鼠海马区细胞和中间神经元的测定 进行空间导航。乙醇将通过以下途径在当地使用 海马内微透析，以及海马区内细胞的激发 将检查透析区。在具体目标2中， 全身性(腹膜)注射乙醇对大鼠点燃的影响 大鼠海马区细胞和中间神经元的测定 进行空间导航。在特定目标3中，海马区 乙醇在局部使用后的浓度 将确定微透析及其全身给药。这 神经化学研究将确保在特定目标下产生的数据 将对1和2进行适当的比较和解释。

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.