LINKING PRESYNAPTIC PLASTICITY TO SLEEP HOMEOSTASIS AND EVOLUTION

Sleep is a highly conserved behavior that rapidly adapts to environmental change. Yet, the expression of sleep homeostasis varies widely across species and populations. Sleep plasticity and homeostatic regulation have been linked to changes in synaptic transmission, but the underlying mechanisms remain poorly understood. In particular, it is unclear how sleep modulates specific synaptic properties and how this coupling is shaped by distinct evolutionary pressures across populations. Here, we integrated high-resolution sleep phenotyping, synaptic physiology, and comparative evolutionary analyses in Drosophila melanogaster larvae to investigate the relationship between sleep behavior, synaptic plasticity, and evolution. We observed robust sleep deprivation and a homeostatic sleep rebound following both temperature elevation and aversive auditory stimulation. Sleep deprivation and rebound were driven by changes in sleep episode number, indicating changes in sleep quality. Strikingly, electrophysiological recordings at the larval neuromuscular junction revealed that sleep deprivation increases action potential-evoked presynaptic release following thermal or auditory stimulation. Moreover, presynaptic release decreased compared to controls during the homeostatic sleep rebound, suggesting bidirectional presynaptic plasticity. D. melanogaster populations experimentally adapted to high temperature for X generations showed neither sleep loss nor rebound under thermal challenge, consistent with evolutionary modulation of behavioral plasticity. Together, these results link sleep homeostasis to presynaptic plasticity and suggest that sleep behavior is shaped by evolutionary pressure.