Jiso Hong 1, David E. Lozano 1, Kevin T. Beier 2, Shinjae Chung 1 & Franz Weber 1 *
1Department of Neuroscience, Perelman School of Medicine, Chronobiology and Sleep Institute, University of Pennsylvania, Philadelphia, PA, USA.
2Department of Physiology and Biophysics, School of Medicine, University of California, Irvine, Irvine, CA, USA.
*Corresponding author: correspondence to Franz Weber
Rapid eye movement (REM) sleep is accompanied by intense cortical activity, underlying its wake-like electroencephalogram. The neural activity inducing REM sleep is thought to originate from subcortical circuits in brainstem and hypothalamus. However, whether cortical neurons can also trigger REM sleep has remained unknown. Here we show in mice that the medial prefrontal cortex (mPFC) strongly promotes REM sleep. Bidirectional optogenetic manipulations demonstrate that excitatory mPFC neurons promote REM sleep through their projections to the lateral hypothalamus and regulate phasic events, reflected in accelerated electroencephalogram theta oscillations and increased eye movement density during REM sleep. Calcium imaging reveals that the majority of lateral hypothalamus-projecting mPFC neurons are maximally activated during REM sleep and a subpopulation is recruited during phasic theta accelerations. Our results delineate a cortico-hypothalamic circuit for the top-down control of REM sleep and identify a critical role of the mPFC in regulating phasic events during REM sleep.