PT  - JOURNAL ARTICLE
AU  - Abhilash, Lakshman
AU  - Shafer, Orie Thomas
TI  - Circadian Regulation of Sleep in <em>Drosophila</em>: Insights from a Two-Process Model
AID  - 10.1101/2022.08.12.503775
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.08.12.503775
4099  - http://biorxiv.org/content/early/2022/08/15/2022.08.12.503775.short
4100  - http://biorxiv.org/content/early/2022/08/15/2022.08.12.503775.full
AB  - Sleep is largely controlled by two processes – a circadian clock that regulates its timing and a homeostat that regulates the drive to sleep. Drosophila has been a useful model for understanding the molecular and neuronal control of circadian rhythms, and more recently, also for the homeostatic control of sleep. Consequently, mechanisms underlying both the circadian and the homeostatic processes regulating sleep have been characterized. Borbély and Daan’s two-process model has provided a powerful quantitative framework for understanding how circadian and homeostatic processes converge to regulate sleep for four decades. Despite the clear utility of this model for understanding mammalian sleep regulation, the field of fly sleep has not employed a formal two-process model as a framework for the investigation of sleep control. To this end, we have adapted the two-process model to fly sleep. In this study, we establish the utility of this model by showing that it can provide empirically testable predictions regarding both the circadian and homeostatic control of fly sleep. Using this model, 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. Though a two-process model in which the circadian and homeostatic components act independently captures most aspects of sleep remarkably well, we found that increasing the rates of sleep pressure changes when circadian clocks run faster produced better fits between predicted and observed sleep rhythms. Finally, our results indicate that longer sleep bouts better reflect the homeostatic process than the current unitary definition of sleep as any bout of inactivity lasting five minutes or more. This simple two-process model represents a powerful theoretical framework for future work on the molecular and physiological regulation of fly sleep.Competing Interest StatementThe authors have declared no competing interest.