Abstract
BackgroundThe 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 GABAA receptors (Rs) and inhibitory transmission undergo dynamic changes as a function of prior activity, we investigated whether the GABAARs on cholinergic cells might undergo such changes as a function of their prior activity during waking vs. sleep.ResultsIn 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 β2–3 subunit GABAARs on choline acetyltransferase (ChAT) immunopositive (+) cells in the magnocellular BF. In sections also stained for c-Fos, β2–3 GABAARs 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 β2–3 GABAARs 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.ConclusionWe conclude that membrane GABAARs 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 GABAARs 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.
Highlights
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
C-Fos and GABAAR immunostaining in cholinergic cells across conditions Within sections triple-immunostained for c-Fos, choline acetyltransferase (ChAT) and β2–3GABAARs, ChAT immunopositive (+) cells which expressed c-Fos were present in sleep deprivation (SD) brains within the magnocellular preoptic nucleus (MCPO) in small numbers and virtually absent in sleep in control (SC) and sleep recovery (SR) brains, as previously reported for all BF cholinergic nuclei [5]
In the SD brains, c-Fos+/ChAT+ cells appeared positively immunostained for the β2–3 GABAAR, which was concentrated over the plasma membrane of the cell (Fig. 1A)
Summary
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. Recorded and labeled using the juxtacellular technique, the cholinergic neurons discharge maximally in association with cortical activation during active waking and rapid eye movement (REM) sleep [3,4] They cease firing in association with cortical slow wave activity during quiet, non-REM (NREM) sleep. As evidenced by increases in the amount of sleep and in the power of slow wave activity that occur following deprivation, sleep is considered to be under homeostatic control [11,12,13] Such control could be determined by similar processes that serve to maintain long term stability in the excitability and activity of neurons and their circuits [14,15]. We envisaged that the changes in activity that occur in specific cell groups during waking and sleep could be associated with dynamic changes in GABAARs and resulting inhibition
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