Astrocytic Ca2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep

Daniel M. Bjørnstad,Anna R. Chambers,Erlend A. Nagelhus,Gudmund Horn Hermansen,Koen Vervaeke,Laura Bojarskaite,Knut Sindre Åbjørsbråten,Wannan Tang,Rolf Sprengel,Rune Enger,Klas H. Pettersen,Céline Cunen

doi:10.1038/s41467-020-17062-2

Abstract

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. Here, we employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. We show that astrocytic Ca2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during sleep compared to wakefulness. Moreover, an increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Finally, genetic ablation of an important astrocytic Ca2+ signaling pathway impairs slow wave sleep and results in an increased number of microarousals, abnormal brain rhythms, and an increased frequency of slow wave sleep state transitions and sleep spindles. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep.

Highlights

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep
We show that Ca2+ signaling in astrocytes is reduced during sleep compared to wakefulness and exhibits distinct characteristics across sleep states
Imaging was performed at a frame rate of 30 Hz, in accordance with recent reports underscoring the importance of high image acquisition rates for capturing fast populations of astrocytic Ca2+ events[17]

Summary

Introduction

Astrocytic Ca2+ signaling has been intensively studied in health and disease but has not been quantified during natural sleep. We employ an activity-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca2+ activity, brain rhythms and behavior. An increase in astrocytic Ca2+ signaling precedes transitions from slow wave sleep to wakefulness, with a peak upon awakening exceeding the levels during whisking and locomotion. Our findings demonstrate an essential role for astrocytic Ca2+ signaling in regulating slow wave sleep. We characterize astrocytic Ca2+ signaling in mice during natural head-fixed sleep using an automated activity-based analysis tool. We show that Ca2+ signaling in astrocytes is reduced during sleep compared to wakefulness and exhibits distinct characteristics across sleep states. An increase in astrocytic Ca2+ signaling precedes transition from slow wave sleep (SWS)—but not rapid eye movement (REM) sleep—to wakefulness. Our data indicate a role for astrocytic Ca2+ signaling in regulating SWS

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Conclusion