The objective of the proposed research is to study the effects of acute doses of ethanol on the electrical parameters of neuronal membrane and the mechanisms leading to the long-term effects of ethanol. The electrical membrane properties are essential parameters of neuronal integration in the central nervous system. This concept of integration deals with the effectiveness of synaptic inputs and their summation in the dendrites, and relies on the electrotonic properties of neuronal membrane. Although acute ethanol intoxication causes deficits in memory and information processing, very little is known about the effects of ethanol on neuronal integration. Preliminary studies in the hippocampus have suggested that clinically relevant acute doses of ethanol (20 to 100mM) increase the membrane capacitance of CA1 pyramidal cells. However, the determination of the electrical membrane properties requires detailed analysis of the morphological and electrical structure of the neurons studied. Therefore, the first objective is to measure the acute effects of clinically relevant doses of ethanol (20 to 100mM) on the electrical membrane properties of granule cells in the dentate gyrus using the in-vitro hippocampal slice preparation. This preparation is particularly useful, because it allows direct access to the neurons for intracellular records, morphological identification of the same cell, and the ethanol containing solution can be applied directly on the tissue slice. The second objective is to analyze the effect of ethanol on neuronal integration with computer modeling techniques applied to th granule cells. Powerful computer models of neurons have been developed to accurately simulate neuronal behavior. The effects of ethanol on the membrane properties and other electrophysiological parameters will be implemented to study the interaction between both acute and long-term effects of ethanol and neuronal integration. Chronic ethanol treatment (5 months) also affects the membrane electrotonic parameters and particularly a decrease in the membrane specific capacitance of granule cells was measured. However, the mechanisms leading to the development of long-term effects are unknown. Acute tolerance (adaptation during the course of a single ethanol exposure) has been reported to share the same mechanisms with chronic tolerance (adaptation during continuous presence of ethanol). The final objective is to measure the electrical neuronal parameters during this acute tolerance phase in order to understand the process leading to long-term effects of ethanol.
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