This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sleep perturbations by ethanol play a key role in the progression of alcoholism, and are predictive of relapse. For some insomniacs, the sedative effects of ethanol are the pathway to bedtime alcohol consumption and eventual abuse. Continued abuse of ethanol leads to long-term changes in neuronal sleep circuitry that last well beyond the cessation of ethanol administration. The overall goal of this project is to determine key molecular events that underlie cellular adaptation of sleep circuitry to alcohol, and to correlate them with functional changes in sleep physiology. The thalamus is an integral participant in the generation of sleep/wake cycles and the brain rhythms that occur during sleep. One of the best understood of these rhythms is the thalamic spindle oscillation associated with Stage II sleep. In alcoholics, spindle waves are diminished and are replaced with less-restful random eye movement (REM) sleep. Understanding the fate of spindle wave sleep is thus a vital question that directly relates to the reinforcement effects of ethanol, since some alcoholics return to drinking in an effort to improve the quality of their sleep. The spindle waves generated by thalamocortical relay cells are the output of a complex network oscillation that is propagated throughout the brain. The engine that allows spindle waves to flow through the brain is a low threshold calcium current mediated by T-type calcium channels. Based on our previous studies thalamic T-type calcium channels appear particularly sensitive to ethanol exposure and the disruption of their function and/or availability may provide a cellular mechanism to explain why the sleep of alcoholics is disrupted. To test this hypothesis, we are examining whether the electrophysiological properties and/or the relative expression of the thalamic T channels are affected in Long-Evans rats undergoing chronic ethanol self-administration.
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