Dynamic changes in GABA(A )receptors on basal forebrain cholinergic neurons following sleep deprivation and recovery

BACKGROUND: The basal forebrain (BF) cholinergic neurons play an important role in cortical activation and arousal and are active in association with cortical activation of waking and inactive in association with cortical slow wave activity of sleep. In view of findings that GABA(A )receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABA(A)Rs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep. RESULTS: In the brains of rats under sleep control (SC), sleep deprivation (SD) or sleep recovery (SR) conditions in the 3 hours prior to sacrifice, we examined immunofluorescent staining for β(2–3 )subunit GABA(A)Rs on choline acetyltransferase (ChAT) immunopositive (+) cells in the magnocellular BF. In sections also stained for c-Fos, β(2–3 )GABA(A)Rs were present on ChAT+ neurons which expressed c-Fos in the SD group alone and were variable or undetectable on other ChAT+ cells across groups. In dual-immunostained sections, the luminance of β(2–3 )GABA(A)Rs over the membrane of ChAT+ cells was found to vary significantly across conditions and to be significantly higher in SD than SC or SR groups. CONCLUSION: We conclude that membrane GABA(A)Rs increase on cholinergic cells as a result of activity during sustained waking and reciprocally decrease as a result of inactivity during sleep. These changes in membrane GABA(A)Rs would be associated with increased GABA-mediated inhibition of cholinergic cells following prolonged waking and diminished inhibition following sleep and could thus reflect a homeostatic process regulating cholinergic cell activity and thereby indirectly cortical activity across the sleep-waking cycle.