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

Abstract

Astrocytic Ca 2+ 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 Ca 2+ signals in the neocortex of awake and naturally sleeping mice while monitoring neuronal Ca 2+ activity, brain rhythms and behavior. We show that astrocytic Ca 2+ signals exhibit distinct features across the sleep-wake cycle and are reduced during 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. Finally, genetic ablation of an important astrocytic Ca 2+ 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 Ca 2+ signaling in regulating slow wave sleep.

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“… 8 New studies done by Erlend Nagelhus and colleagues also show that Ca2+ signalling is essential in the regulation of slow wave sleep. 9 All of these new studies support that astrocytes are key elements in the regulation of brain function. Emerging evidence indicates that disturbed sleep might be among the strongest risk factors for development of neurodegenerative diseases.…”

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“…One major contributor to the pathogenesis of AD is neuroinflammation although its role in AD is not entirely known. However, accumulating evidence points to microglial and astrocytes whose regulation of CNS response to injury through pro or anti-inflammatory signals have been strongly implicated [ 285 , 286 , 287 ]. It is postulated the Aβ plaques stimulate astrocytes and microglial to secrete pro-inflammatory cytokines, chemokines, and reactive oxygen species whose chronic presence dysregulate the immune response that furthers neurodegeneration.…”

Deformable mirror-based axial scanning for two-photon mammalian brain imaging

“…These include astrocytes, the largest class of non-neuronal brain cells which are largely electrically silent but which exhibit spatiotemporally rich Ca 2þ dynamics. 4,5 These astrocytic Ca 2þ dynamics have been shown to be critical for astrocytic regulation of brain states related to sleep 4,6 and attention. 7 To expand our understanding of the roles of astrocytes in neural circuits, there is a need to develop optical tools that are tailored specifically to capture astrocytic Ca 2þ physiology.…”