Molecular mechanisms of sleep homeostasis in flies and mammals

Sleep is homeostatically regulated with sleep pressure accumulating with the increasing duration of prior wakefulness. Yet, a clear understanding of the molecular components of the homeostat, as well as the molecular and cellular processes they sense and control to regulate sleep intensity and duration, remain a mystery. Here,we will discuss the cellular and molecular basis of sleep homeostasis, first focusing on the best homeostatic sleep marker in vertebrates, slow wave activity; second, moving to the molecular genetic analysis of sleep homeostasis in the fruit fly Drosophila; and, finally, discussing more systemic aspects of sleep homeostasis.