| First Author | Bell BJ | Year | 2020 |
| Journal | bioRxiv | Mgi Jnum | J:312000 |
| Mgi Id | MGI:6782385 | Doi | 10.1101/2020.03.12.989921 |
| Citation | Bell BJ, et al. (2020) A clock-driven neural network critical for arousal. bioRxiv |
| abstractText | The daily cycling of sleep and arousal states are among the most prominent biological rhythms under circadian control. While much is known about the core circadian clock1,2, how this clock regulates sleep and arousal remains poorly understood3. In Drosophila, we previously characterized WIDE AWAKE (WAKE), a clock-output molecule that promotes sleep at night4,5. Here, we show that the function of WAKE is conserved in mice and that mWAKE+ neurons comprise a clock-regulated arousal system. Besides the suprachiasmatic nucleus (SCN), mWAKE is expressed in the dorsomedial hypothalamus (DMH) and other arousal-related regions. mWAKE mutants exhibit increased spiking of mWAKE+ neurons and increased behavioural arousal at night. In the DMH, mWAKE labels a novel circuit that promotes wakefulness and is required for rapid eye-movement sleep. Single-cell sequencing, immunostaining, and patch-clamp experiments reveal that mWAKE+ neurons constitute a glutamatergic/gabaergic population that projects widely, receives neuromodulatory input, and acts on neuromodulatory neurons. Strikingly, broad chemogenetic silencing of mWAKE+ cells leads to profound loss of behavioural responsiveness and low amplitude, low frequency electroencephalography waveforms. These findings suggest that the genetic mechanisms regulating circadian control of sleep and arousal are conserved across >500 million years of evolution and define a clock-regulated neural network critical for arousal. |
