Is REM sleep a paradoxical state?: Different neurons are activated in the cingulate cortices and the claustrum during wakefulness and paradoxical sleep hypersomnia

Michel Jouvet proposed in 1959 that REM sleep is a paradoxical state since it was characterized by the association of a cortical activation similar to wakefulness (W) with muscle atonia. Recently, we showed using cFos as a marker of activity that cortical activation during paradoxical sleep (PS) was limited to a few limbic cortical structures in contrast to W during which all cortices were strongly activated. However, we were not able to demonstrate whether the same neurons are activated during PS and W and to rule out that the activation observed was not linked with stress induced by the flowerpot method of PS deprivation. In the present study, we answered to these two questions by combining tdTomato and cFos immunostaining in the innovative TRAP2 transgenic mice exposed one week apart to two periods of W (W-W mice), PS rebound (PSR-PSR) or a period of W followed by a period of PSR (W-PSR mice). Using such method, we showed that different neurons are activated during W and PSR in the anterior cingulate (ACA) and rostral and caudal retrosplenial (rRSP and cRSP) cortices as well as the claustrum (CLA) previously shown to contain a large number of activated neurons after PSR. Further, the distribution of the neurons during PSR in the rRSP and cRSP was limited to the superficial layers while it was widespread across all layers during W. Our results clearly show at the cellular level that PS and W are two completely different states in term of neocortical activation.