Cortical regulation of two-stage rapid eye movement sleep

Rapid eye movement (REM) sleep is a sleep state characterized by skeletal muscle paralysis and cerebral cortical activation. Yet, global cortical dynamics and their role in regulating REM sleep remain unclear. Here we show that in mice, REM sleep is accompanied by highly patterned cortical activity waves, with the retrosplenial cortex (RSC) as a major initiation site. Two-photon imaging of layer 2/3 pyramidal neurons of the RSC revealed two distinct patterns of population activities during REM sleep. These activities encoded two sequential REM sleep substages, characterized by contrasting facial movement and autonomic activity and by distinguishable electroencephalogram theta oscillations. Closed-loop optogenetic inactivation of RSC during REM sleep altered cortical activity dynamics and shortened REM sleep duration via inhibition of the REM substage transition. These results highlight an important role for the RSC in dictating cortical dynamics and regulating REM sleep progression.