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

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.