RT Journal Article SR Electronic T1 A two-process model of Drosophila sleep reveals an inter-dependence between circadian clock speed and the rate of sleep pressure decay JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.08.12.503775 DO 10.1101/2022.08.12.503775 A1 Abhilash, Lakshman A1 Shafer, Orie Thomas YR 2023 UL http://biorxiv.org/content/early/2023/08/10/2022.08.12.503775.abstract AB Sleep is controlled by two processes – a circadian clock that regulates its timing and a homeostat that regulates the drive to sleep. Drosophila has been an insightful model for understanding both processes. For four decades, Borbély and Daan’s two-process model has provided a powerful framework for understanding how circadian and homeostatic processes regulate sleep. However, the field of fly sleep has not employed such a model as a framework for the investigation of sleep. To this end, we have adapted the two-process model to the fly and establish its utility by showing that it can provide empirically testable predictions regarding the circadian and homeostatic control of fly sleep. We show that the ultradian rhythms previously reported for loss-of-function clock mutants are a predictable consequence of a functional sleep homeostat in the absence of a functioning circadian system. We find that a model in which the circadian clock speed and homeostatic rates act without influencing each other provides imprecise predictions regarding how clock speed influences the strength of sleep rhythms and the amount of daily sleep. We also find that quantitatively good fits between empirical values and model predictions were achieved only when clock speeds were positively correlated with rates of decay of sleep pressure. Our results indicate that longer sleep bouts better reflect the homeostatic process than the current definition of sleep as any inactivity lasting five minutes or more. This two-process model represents a powerful framework for future work on the molecular and physiological regulation of fly sleep.Competing Interest StatementThe authors have declared no competing interest.