GABAergic parafacial zone is a medullary slow–wave–sleep promoting center

Work in animals and humans suggest the existence of a slow–wave sleep (SWS) promoting/EEG synchronizing center in the mammalian lower brainstem. While sleep–active GABAergic neurons in the medullary parafacial zone (PZ) are needed for normal SWS, it remains unclear if these neurons can initiate and maintain SWS or EEG slow wave activity (SWA) in behaving mice. We used genetically targeted activation and optogenetic–based mapping to uncover the downstream circuitry engaged by SWS–promoting PZ neurons, and we show that this circuit uniquely and potently initiates SWS and EEG SWA, regardless of the time of day. PZ neurons monosynaptically innervate and release synaptic GABA onto parabrachial neurons that in turn project to and release synaptic glutamate onto cortically–projecting neurons of the magnocellular basal forebrain; hence a circuit substrate is in place through which GABAergic PZ neurons can potently trigger SWS and modulate the cortical EEG.