Molecular Mechanisms of Sleep Homeostasis in Flies and Mammals

Abstract

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.

Figure 1.

Model for the relationship between sleep and the immune system. In both flies and mammals, loss of sleep increases expression of nuclear factor κB (NF-κB) in mammals by increasing cytokine expression and in Drosophila through unknown mechanisms. The same immune/inflammation molecules are increased by infection. Cytokines or NF-κB, in turn, increase sleep in both systems, and increased sleep is associated with increased survival. IL-1, Interleukin 1; TNF-α, tumor necrosis factor α.