Mark Wu, MD, PhD
Associate Professor of Neurology,
Johns Hopkins University
Host: Nirao Shah
While the molecular underpinnings of the core circadian clock are now well-established, how this oscillator regulates downstream behaviors is less understood. Arguably the most prominent of these downstream behaviors are sleep/wake states. Over the past decade, our lab has been studying the molecular and circuit mechanisms by which the circadian clock regulates sleep and arousal. From a large-scale forward genetic screen in Drosophila, we identified a novel clock output molecule named WIDE AWAKE (WAKE). We have shown that WAKE acts downstream of the clock to regulate sleep by rhythmically tuning the activity of arousal-promoting clock neurons. We now show that these mechanisms are conserved in mammals. Moreover, using chemogenetic, optogenetic, and electrophysiological approaches, we have characterized the regulation and function of WAKE+ circuits in mice. These data suggest that WAKE defines a novel neural circuit in mice that bidirectionally interacts with neuromodulatory networks and is required for arousal. Together, these studies establish conserved mechanisms by which the circadian clock regulates sleep and reveal a new neural network that is essential for arousal.
 Masashi Tabuchi, Joseph D. Monaco, Grace Duan, Benjamin Bell, Sha Liu, Qili Liu,1 Kechen Zhang,and Mark N. Wu. Clock-Generated Temporal Codes Determine Synaptic Plasticity to Control Sleep. Cell 175 1-15. 2018 DOI: 10.1016/j.cell.2018.09.016