Insights Into Sleep Homeostasis From A Drosophila Genetic Screen For Sleep Rebound Mutants

Sleep rebound – the increase in sleep that follows sleep deprivation (SD) – is a hallmark of homeostatic sleep regulation that is conserved across the animal kingdom. However, both the mechanisms that underlie sleep rebound and its relationship to other forms of homeostatic sleep regulation remain unclear. To identify mechanisms important for sleep rebound, we developed a novel method of inducing SD in Drosophila by thermogenetically activating wake-promoting neurons. We then used this method to conduct a large-scale genetic screen to identify Drosophila mutants with reduced sleep rebound. In Chapter 1, we discuss the use of Drosophila melanogaster as a model organism in sleep research. In Chapter 2, we discuss results of the genetic screen, where we find that sleep rebound and habitual sleep amount are controlled by separate genetic factors. In Chapter 3, we present data suggesting that mutants with reduced sleep rebound experience a milder wake-promoting stimulus during the sleep deprivation period compared to control flies, and that this difference in the strength of the wake-promoting stimulus is likely responsible for the reduced rebound phenotype. In Chapter 4, we discuss the implications of these data, and future directions to explore a model where homeostatic plasticity in the neural circuit used to produce sleep loss is responsible for subsequent rebound. These findings have important implications for our understanding of sleep and provide a model for homeostatic sleep regulation that could apply to mammalian systems