Calcineurin goes to sleep

The need for sleep is evolutionarily conserved across animals. During sleep, animals give up opportunities for food, water, and sex, and become more vulnerable to predation. Although we know why we eat, drink, or reproduce, we do not yet know why we sleep. The ubiquity of sleep across species suggests 1) an ancient origin of sleep, perhaps coincident with the evolution of the first nervous system(s), and 2) that sleep must provide an essential function, or functions, maintained through hundreds of millions of years of animal evolution. Increasingly, sleep is understood to be a fundamental pillar of health, as insufficient sleep amount or quality increases the risk of numerous neuropsychiatric, metabolic, and immune conditions. Therefore, understanding the molecular basis for the need to sleep remains an essential research question to advance basic biology and human health. In this issue of PNAS, Yin et al. use mice to identify the evolutionarily conserved phosphatase calcineurin as a critical regulator of baseline sleep and homeostatic increase in sleep depth following sleep deprivation. Indeed, Yin et al. showed that increased or decreased calcineurin activity in neurons drives a striking increase (~100%) or decrease (~70%) in baseline sleep respectively, and near abrogation of homeostatic sleep response upon calcineurin ablation.