Long-term multichannel recordings in Drosophila flies reveal distinct responses to deviant visual stimuli during sleep compared to wake

During sleep, behavioral responsiveness to external stimuli is decreased. This classical definition of sleep has been applied effectively across the animal kingdom to identify this common behavioral state in a growing list of creatures, from mammals to invertebrates. Yet it remains unclear whether decreased behavioral responsiveness during sleep is necessarily associated with decreased responsiveness in brain activity, especially in relative latecomers to the sleep field, such as insects. Here, we perform long-term multichannel electrophysiology in tethered Drosophila melanogaster flies exposed continuously to flashing visual stimuli. Flies were still able to sleep under these visual stimulation conditions, as determined by traditional immobility duration criteria for the field. Interestingly, local field potentials (LFPs) recorded in a transect through the fly brain failed to show any difference in amplitude during sleep compared to wake when the visual stimuli were invariant. In contrast, LFP responses were lower when visual stimuli were variable and of lower probability, especially in the central brain. Central brain responses to deviant stimuli were lowest during the deepest stage of sleep, characterized by more regular proboscis extensions. This shows that the sleeping fly brain processes low-probability visual stimuli in a different way than more repeated stimuli and presents Drosophila as a model system for studying the potential role of sleep in regulating predictive processing. SUMMARY STATEMENTThe sleeping fly brain still responds to visual stimuli. However, response amplitudes depend on stimulus history and probability, as well as recording location.