Activation of the GABAergic Parafacial Zone Maintains Sleep and Counteracts the Wake-Promoting Action of the Psychostimulants Armodafinil and Caffeine.

We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZ) neurons in behaving mice produces slow-wave-sleep (SWS), even in the absence of sleep deficit, suggesting that these neurons may represent, at least in part, a key cellular substrate underlying sleep drive. It remains, however, to be determined if PZ neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZ neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, armodafinil or caffeine. We found that activation of PZ neurons completely blocked the behavioral and electrocortical wake-promoting action of armodafinil. In some contrast, activation of PZ neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZ neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) armodafinil cannot exert its wake-promoting effects when PZ neurons are activated, intimating a possible shared circuit/molecular basis for mechanism of action; (3) caffeine can continue to exert potent cortical desynchronizing, but not behavioral, effects when PZ neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZ neurons represent a key cell population for SWS induction and maintenance.