Paradoxical sleep in mice lacking M3 and M2/M4 muscarinic receptors

Acetylcholine is crucial for the regulation of paradoxical sleep (PS) and EEG theta activity. To determine the contribution of individual muscarinic receptors to these events, we analyzed the sleep-waking cycle and EEG activities of mice lacking functional M(3) or M(2)/M(4 )receptors. Daily PS amounts were significantly decreased in M3-/- (-22%) but not in M2/M4-/- mice. Further, the theta peak frequency for PS was significantly increased in both M2/M4-/- and M3-/- mice. This study supports the potential role of M(3) rather than M(2) and M(4) muscarinic receptors in the modulation of PS in mice and strengthens the idea that multiple muscarinic receptors contribute to the regulation of the EEG theta activity during PS.