Cellular Mechanisms of Ethanol's Influence on Sleep

Carden, Williams

Abstract

Sleep disturbances are common in alcoholic patients, with a number of serious health consequences. The best understood brain rhythm is the spindle waves associated with Stage II sleep, and this specific form of sleep is enhanced with acute alcohol administration. Perhaps the most promising brain region in which to explore alcohol influences on sleep, the thalamus, has been so far ignored. The thalamus is a primary generator of sleep/wake cycles and the brain rhythms that are the hallmark of sleep staging. The mechanisms underlying spindle wave generation depend on a low threshold calcium current (T-current), and dynamic reciprocal connections between excitatory thalamocortical neurons and inhibitory thalamic reticular neurons. The T-current plays such a pivotal role in the generation and maintenance of spindle waves that ethanol's interaction with the T-current is the focus of this proposal. The following specific aims will serve as the training vehicle, and will seek to determine the influence of ethanol on spindle wave circuitry of the thalamus:
Aim 1 : The influence of acute ethanol exposure on the T-current of thalamocortical and thalamic reticular neurons will be examined using an in vitro brain slice preparation. Hypothesis: Ethanol will enhance the T-current in these two neuronal populations, an effect seen in preliminary studies.
Aim 2 : The effect of chronic ethanol exposure on the T-current of thalamocortical and thalamic reticular neurons will be examined using an in vitro brain slice preparation. Hypothesis: Chronic ethanol exposure will result in neuroadaptational decrease in the T-current, which may underlie the decrease in spindle activity seen in alcoholic patients. This research is an opportunity to work out the cellular mechanisms underlying reported perturbations of sleep rhythms by acute and chronic ethanol exposure in a new, yet well-characterized and accessible model system.