Sleep and circadian rhythms: Evolutionary entanglement and local regulation

Circadian rhythms evolved within single cell organisms and serve to regulate rest-activity cycles in most single-cell and multiple-cell organisms. In contrast, sleep is a network emergent property found in animals with a nervous system. Rhythms and sleep are much entangled involving shared regulatory molecules such as adenosine, ATP, cytokines, neurotrophins, and nitric oxide. These molecules are activity-dependent and act locally to initiate regulatory events involved in rhythms, sleep, and plasticity.