Chronic ethanol abuse leads to long-term changes in sleep circuitry that last well beyond the cessation of ethanol administration. Two brain regions are particularly important for the initiation and maintenance of sleep. The suprachiasmatic nucleus (SCN) is the primary initiator of sleep/wake cycles and the thalamus is involved in the generation and maintenance of brain rhythms that occur during sleep. The following specific aims will serve as the training vehicle and will seek to determine the cellular and molecular influence of ethanol on sleep and circadian rhythms.
Aim 1 : Behavioral alterations in chronic drinkers. I hypothesize a decrease in total sleep time and shifts in circadian phase (delays) in chronic drinkers and animals administered ethosuximide.
Aim 2 : Molecular alterations in chronic drinkers. I hypothesize that the changes in sleep and circadian rhythms observed in Aim 1, will be correlated with changes in gene (increased) and protein (decreased) expression in both thalamic and SCN T channel isoforms, as well as in SCN molecular clock genes and proteins (attenuation and loss of pronounced rhythmicity of gene and protein expression).
Aim 3 : Electrophysiological characterization of the T-channel in chronic drinking mice. I hypothesize a neuroadaptational decrease in T-current that may underlie the decrease in spindle wave oscillations reported in alcoholic patients. This research will afford me the opportunity to understand how chronic ethanol consumption alters the mechanisms underlying the reported disruptions in sleep circuitry.
| Nordskog, B K; Hammarback, J A; Godwin, D W (2006) Diurnal gene expression patterns of T-type calcium channels and their modulation by ethanol. Neuroscience 141:1365-73 |
