Ketema Paul: University of California, Los Angeles

Sleep loss can severely impair cognitive performance, yet the ability to recover from sleep loss is not well understood. Sleep regulatory mechanisms are assumed to lie exclusively within the brain mainly due to the strong behavioral manifestations of sleep. Whole-body disruptions of circadian biological clocks in mice are known to impair several aspects of sleep. Surprisingly, we found that circadian-dependent sleep phenotypes were not rescued by restoring clock function in the brains of these mice. Instead, we found that most of the impaired sleep phenotypes could be rescued by restoring circadian clock function exclusively in skeletal muscle. Additionally, selective overexpression or knockout of core circadian gene Bmal1 in skeletal muscle had distinct and opposing effects on sleep traits. The most robust effects of Bmal1 manipulation in skeletal muscle tissue were on the ability to recover from sleep loss. Overall, these results suggest that molecular mechanisms in the periphery in general, and skeletal muscle tissue in particular, have regulatory influences on sleep-wake mechanisms in the brain.