Cold Inducible RNA-binding protein (CIRBP) adjusts clock gene expression and REM sleep recovery after sleep deprivation

Abstract

Sleep depriving mice affects clock gene expression, suggesting that these genes partake in sleep homeostasis. The mechanisms linking wakefulness to clock gene expression are, however, not well understood. We propose CIRBP because its rhythmic expression is i) sleep-wake driven and ii) necessary for high-amplitude clock gene expression in vitro. We therefore expect Cirbp knock-out (KO) mice to exhibit attenuated sleep-deprivation (SD) induced changes in clock gene expression, and consequently to differ in their sleep homeostatic regulation. Lack of CIRBP indeed blunted the SD-incurred changes in cortical expression of the clock gene Rev-erb whereas it amplified the changes in Per2 and Clock. Concerning sleep homeostasis, KO mice accrued only half the extra REM sleep wild-type (WT) littermates obtained during recovery. Unexpectedly, KO mice were more active during lights-off which was accompanied by an acceleration of theta oscillations. Thus, CIRBP adjusts cortical clock gene expression after SD and expedites REM sleep recovery.