A clock-dependent brake for rhythmic arousal in the dorsomedial hypothalamus.

ABSTRACT: Circadian clocks generate rhythms of arousal, but the underlying molecular and cellular mechanisms remain unclear. In Drosophila, the clock output molecule WIDE AWAKE (WAKE) labels rhythmic neural networks and cyclically regulates sleep and arousal. Here, we show, in a male mouse model, that mWAKE/ANKFN1 labels a subpopulation of dorsomedial hypothalamus (DMH) neurons involved in rhythmic arousal and acts in the DMH to reduce arousal at night. In vivo Ca²⁺ imaging reveals elevated DMH^mWAKE activity during wakefulness and rapid eye movement (REM) sleep, while patch-clamp recordings show that DMH^mWAKE neurons fire more frequently at night. Chemogenetic manipulations demonstrate that DMH^mWAKE neurons are necessary and sufficient for arousal. Single-

SUBMITTER: Liu Q 

PROVIDER: S-EPMC10567910 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature