Experimentally induced active and quiet sleep engage non-overlapping transcriptional programs in Drosophila

Abstract

Sleep in mammals is broadly classified into two different categories: rapid eye movement (REM) sleep and slow wave sleep (SWS), and accordingly REM and SWS are thought to achieve a different set of functions. The fruit fly Drosophila melanogaster is increasingly being used as a model to understand sleep functions, although it remains unclear if the fly brain also engages in different kinds of sleep as well. Here, we compare two commonly used approaches for studying sleep experimentally in Drosophila: optogenetic activation of sleep-promoting neurons and provision of a sleep-promoting drug, Gaboxadol. We find that these different sleep-induction methods have similar effects on increasing sleep duration, but divergent effects on brain activity. Transcriptomic analysis reveals that drug-induced deep sleep (‘quiet’ sleep) mostly downregulates metabolism genes, whereas optogenetic ‘active’ sleep upregulates a wide range of genes relevant to normal waking functions. This suggests that optogenetics and pharmacological induction of sleep in Drosophila promote different features of sleep, which engage different sets of genes to achieve their respective functions.

Multivariate classification of multichannel long-term electrophysiology data identifies different sleep stages in fruit flies

“…In addition, the effect observed during induced sleep was only observed in the central channels, whereas the spontaneous sleep effects appear to at least cover the entire hemisphere from center to periphery. This shows that genetically induced sleep in flies can produce notably different electrophysiological signatures than spontaneous sleep, consistent with several previous similar observations ( 12 , 17 , 36 – 38 ). For the rest of this current study, we focus on spontaneous sleep.…”

“…Our multichannel recordings also revealed that changes in sleep physiology are likely to encompass the entire fly brain, from the optic lobes to the central complex. This is consistent with a recent study where we found that experimentally induced “quiet” and active sleep engaged different whole-brain transcriptional programs ( 36 ). That the whole insect brain “sleeps” is also consistent with other studies, although this has not been previously demonstrated using a comprehensive multichannel approach.…”

“…This suggests that PEs occurring during sleep are qualitatively different from identical PE events occurring during wake. This suggests that the brain activity state [e.g., quiet or deep sleep ( 17 , 36 )] overrides the neural correlates associated with the same behavior occurring during wake.…”