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

ABSTRACT: We previously reported that acute and selective activation of GABA-releasing parafacial zone (PZ^Vgat) 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^Vgat neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZ^Vgat 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^Vgat neurons completely blocked the behavioral and electrocortical wake-promoting action of armodafinil. In some contrast, activation of PZ^Vgat neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZ^Vgat neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) armodafinil cannot exert its wake-promoting effects when PZ^Vgat 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^Vgat neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZ^Vgat neurons represent a key cell population for SWS induction and maintenance.

SUBMITTER: Anaclet C 

PROVIDER: S-EPMC5729562 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature