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 (PZVgat) 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 PZVgat neurons actively maintain, as oppose to simply gate, SWS. To begin to experimentally address this knowledge gap, we asked whether activation of PZVgat neurons could attenuate or block the wake-promoting effects of two widely used wake-promoting psychostimulants, armodafinil or caffeine. We found that activation of PZVgat neurons completely blocked the behavioral and electrocortical wake-promoting action of armodafinil. In some contrast, activation of PZVgat neurons inhibited the behavioral, but not electrocortical, arousal response to caffeine. These results suggest that: (1) PZVgat neurons actively maintain, as oppose to simply gate, SWS and cortical slow-wave-activity; (2) armodafinil cannot exert its wake-promoting effects when PZVgat 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 PZVgat neurons are activated, inferring a shared and divergent circuit/molecular basis for mechanism of action; and 4) PZVgat neurons represent a key cell population for SWS induction and maintenance

Evidence that natural selection maintains genetic variation for sleep in Drosophila melanogaster

BACKGROUND: Drosophila melanogaster often shows correlations between latitude and phenotypic or genetic variation on different continents, which suggests local adaptation with respect to a heterogeneous environment. Previous phenotypic analyses of latitudinal clines have investigated mainly physiological, morphological, or life-history traits. Here, we studied latitudinal variation in sleep in D. melanogaster populations from North and Central America. In parallel, we used RNA-seq to identify interpopulation gene expression differences. RESULTS: We found that in D. melanogaster the average nighttime sleep bout duration exhibits a latitudinal cline such that sleep bouts of equatorial populations are roughly twice as long as those of temperate populations. Interestingly, this pattern of latitudinal variation is not observed for any daytime measure of activity or sleep. We also found evidence for geographic variation for sunrise anticipation. Our RNA-seq experiment carried out on heads from a low and high latitude population identified a large number of gene expression differences, most of which were time dependent. Differentially expressed genes were enriched in circadian regulated genes and enriched in genes potentially under spatially varying selection. CONCLUSION: Our results are consistent with a mechanistic and selective decoupling of nighttime and daytime activity. Furthermore, the present study suggests that natural selection plays a major role in generating transcriptomic variation associated with circadian behaviors. Finally, we identified genomic variants plausibly causally associated with the observed behavioral and transcriptomic variation. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12862-015-0316-2) contains supplementary material, which is available to authorized users