A Role for Astroglial Calcium in Mammalian Sleep and Sleep Regulation

Ingiosi, Ashley M; Hayworth, Christopher R.; Harvey, Daniel O.; Singletary, Kristan G.; Rempe, Michael J.; Wisor, Jonathan P.; Frank, Marcos G.

doi:10.1016/j.cub.2020.08.052

Cited by 106 publications

(174 citation statements)

References 68 publications

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“…Recent evidence converges on a close connection of these functions with whole-brain processes and systemic regulation pathways. Thus, astrocytes respond to and are able to regulate systemic blood pressure (Marina et al, 2020); they significantly (up to 60%) change their volume during sleep or under anesthesia (Xie et al, 2013); astrocytes play an important role in the clearance of beta-amyloids, a process with mechanisms that are now being actively discussed (Iliff et al, 2012;Abbott et al, 2018;Semyachkina-Glushkovskaya et al, 2018;Mestre et al, 2020); both intracellular and network-level activity of astrocytes are significantly different in sleep and during wakefulness, and activates with locomotion (Bojarskaite et al, 2020;Ingiosi et al, 2020;McCauley et al, 2020). It is important to note that many of the mentioned astrocyte functions are not directly related to neural activity, but are governed by their own regulatory pathways (O'Donnell et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Verisokin

Verveyko

Postnov

et al. 2021

Front. Cell. Neurosci.

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Neuronal firing and neuron-to-neuron synaptic wiring are currently widely described as orchestrated by astrocytes—elaborately ramified glial cells tiling the cortical and hippocampal space into non-overlapping domains, each covering hundreds of individual dendrites and hundreds thousands synapses. A key component to astrocytic signaling is the dynamics of cytosolic Ca2+ which displays multiscale spatiotemporal patterns from short confined elemental Ca2+ events (puffs) to Ca2+ waves expanding through many cells. Here, we synthesize the current understanding of astrocyte morphology, coupling local synaptic activity to astrocytic Ca2+ in perisynaptic astrocytic processes and morphology-defined mechanisms of Ca2+ regulation in a distributed model. To this end, we build simplified realistic data-driven spatial network templates and compile model equations as defined by local cell morphology. The input to the model is spatially uncorrelated stochastic synaptic activity. The proposed modeling approach is validated by statistics of simulated Ca2+ transients at a single cell level. In multicellular templates we observe regular sequences of cell entrainment in Ca2+ waves, as a result of interplay between stochastic input and morphology variability between individual astrocytes. Our approach adds spatial dimension to the existing astrocyte models by employment of realistic morphology while retaining enough flexibility and scalability to be embedded in multiscale heterocellular models of neural tissue. We conclude that the proposed approach provides a useful description of neuron-driven Ca2+-activity in the astrocyte syncytium.

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Section: Introductionmentioning

confidence: 99%

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Verisokin

Verveyko

Postnov

et al. 2021

Front. Cell. Neurosci.

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“…These ‘peripheral’ and ‘central’ sleep homeostats may be synchronized by global changes in neuromodulators ( Frank, 2013 ). This view is supported by findings in mammals and invertebrates, where astrocytes have been shown to track sleep propensity and influence compensatory changes in sleep after SD ( Frank, 2013 ; Ingiosi et al, 2020 ; Liu et al, 2016 ; Blum et al, 2021 ; Halassa et al, 2009 ). Therefore, perhaps we haven't found the ‘sleep homeostat’ because we have been looking in the wrong place.…”

Section: Counterpointmentioning

confidence: 52%

Challenging sleep homeostasis

Frank

2021

Neurobiology of Sleep and Circadian Rhythms

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In this commentary, I play the Devil’s advocate and assume the title of High Contrarian. I intend to be provocative to challenge long-standing ideas about sleep. I blame all on Professor Craig Heller, who taught me to think this way as a graduate student in his laboratory. Scientists should fearlessly jump into the foaming edge of what we know, but also consider how safe are their intellectual harbors. There are many ideas we accept as ‘known’: that sleep is ubiquitous in the animal kingdom, that it serves vital functions, that it plays an essential role in brain plasticity. All of this could be wrong. As one example, I reexamine the idea that sleep is regulated by a mysterious ‘homeostat’ that determines sleep need based on prior wake time.

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“…Several recent studies measuring astrocyte Ca 2+ concentrations during the various sleep/wakefulness states have been reported (Bojarskaite et al, 2020; Ingiosi et al, 2020). These results are in very good agreement with our results showing that astrocytes Ca 2+ concentrations/signals decrease during sleep and increase during wakefulness.…”

Section: Discussionmentioning

confidence: 99%

“…However, astrocytic Ca 2+ dynamics in natural sleep has been poorly understood, although an imaging study demonstrated that general anesthesia disrupts astrocyte Ca 2+ signaling in mice (Thrane et al, 2012). Recent studies have recorded astrocyte Ca 2+ changes during sleep/wakefulness in mice, but to date, data has been limited to that of only the cortex (Bojarskaite et al, 2020; Ingiosi et al, 2020). Accumulating evidence shows that astrocytes are heterogeneous with respect to their transcriptomes and functions among various brain regions as well as among various types of neurons (Chai et al, 2017; Morel et al, 2017; Zeisel et al, 2018; Batiuk et al, 2020; Bayraktar et al, 2020; Lozzi et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Region-specific and state-dependent astrocyte Ca²⁺dynamics during the sleep-wake cycle in mice

Tsunematsu

Sakata

Sanagi

et al. 2020

Preprint

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Neural activity is diverse, and varies depending on brain regions and sleep/wakefulness states. However, whether astrocyte activity differs between sleep/wakefulness states, and whether there are differences in astrocyte activity among brain regions remain poorly understood. In this study, we recorded astrocyte intracellular calcium (Ca2+) concentrations of mice during sleep/wakefulness states in the cortex, hippocampus, hypothalamus, cerebellum, and pons using fiber photometry. For this purpose, male transgenic mice in which their astrocytes specifically express the genetically encoded ratiometric Ca2+ sensor YCnano50 were used. We demonstrated that Ca2+ levels in astrocytes significantly decrease during Rapid Eye Movement (REM) sleep and increase after the onset of wakefulness. In contrast, differences in Ca2+ levels during non-Rapid Eye Movement (NREM) sleep were observed among different brain regions, and no significant decrease was observed in the hypothalamus and pons. Further analyses focusing on the transition between sleep/wakefulness states and correlation analysis with episode duration of REM showed that Ca2+ dynamics differed among brain regions, suggesting the existence of several clusters. To quantify region-specific Ca2+ dynamics, principal component analysis was performed to uncover three clusters; i.e., the first comprised the cortex and hippocampus, the second comprised the cerebellum, and the third comprised the hypothalamus and pons. Our study demonstrated that astrocyte Ca2+ levels change substantially according to sleep/wakefulness states. These changes were generally consistent, unlike neural activity. However, we also clarified that Ca2+ dynamics varies depending on the brain region, implying that astrocytes may play various physiological roles in sleep.Significance statementSleep is an instinctive behavior of many organisms. In the previous five decades, the mechanism of the neural circuits controlling sleep/wakefulness states and the neural activities associated with sleep/wakefulness states in various brain regions have been elucidated. However, whether astrocytes, which are a type of glial cell, change their activity during different sleep/wakefulness states is poorly understood. Here, we demonstrated that dynamic changes in intracellular Ca2+ concentrations occur in the cortex, hippocampus, hypothalamus, cerebellum, and pons of genetically modified mice during natural sleep. Further analyses demonstrated that Ca2+ dynamics slightly differ among different brain regions, implying that the physiological roles of astrocytes in sleep/wakefulness might vary depending on the brain region.

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A Role for Astroglial Calcium in Mammalian Sleep and Sleep Regulation

Cited by 106 publications

References 68 publications

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Challenging sleep homeostasis

Region-specific and state-dependent astrocyte Ca²⁺dynamics during the sleep-wake cycle in mice

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A Role for Astroglial Calcium in Mammalian Sleep and Sleep Regulation

Cited by 106 publications

References 68 publications

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Modeling of Astrocyte Networks: Toward Realistic Topology and Dynamics

Challenging sleep homeostasis

Region-specific and state-dependent astrocyte Ca2+dynamics during the sleep-wake cycle in mice

Contact Info

Product

Resources

About

Region-specific and state-dependent astrocyte Ca²⁺dynamics during the sleep-wake cycle in mice