Ca2+signaling in astrocytes is sleep-wake state specific and modulates sleep

Summary Astrocytic Ca 2+ signaling has been intensively studied in health and disease but remains uncharacterized in sleep. Here, we employed a novel activity-based algorithm to assess astrocytic Ca 2+ signals in the barrel cortex of awake and naturally sleeping mice while monitoring neuronal Ca 2+ activity, brain rhythms and behavior. We discovered that Ca 2+ signaling in astrocytes exhibits distinct features across the sleep-wake cycle and is reduced in sleep compared to wakefulness. Moreover, an increase in astrocytic Ca 2+ signaling precedes transitions from slow-wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Genetic ablation of a key astrocytic Ca 2+ signaling pathway resulted in fragmentation of slow-wave sleep, yet increased the frequency of sleep spindles. Our findings suggest a role for astrocytic Ca 2+ signaling in modulating sleep.