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Astrocytes Play an Important Role in Maintaining Slow Wave Sleep

Astrocytes Play an Important Role in Maintaining Slow Wave Sleep content piece image
Astrocytes expressing a green calcium indicator GCaMP6f. Credit: Laura Bojarskaite, PhD candidate at GliaLab at Letten Center, Institute of Basic Medical Sciences, University of Oslo.
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Data presented by researchers from GliaLab at the Letten Centre at the University of Oslo lends further support that astrocytes are important to assure proper slow wave sleep. This finding that a non-neuronal cell type is crucial for appropriate slow wave sleep will guide future studies aimed at deciphering the mechanisms of and identifying novel treatment strategies for sleep disorders. The results have now been published in the journal Nature Communications and featured in Editors’ Highlights "From Brain to Behavior”.

Sleep is vital for our survival. Everyone can relate to how important sleep is for our optimal health simply by remembering how bad one feels after a single night of bad sleep. Yet even though sleep has been studied for over a century, the precise function of sleep and the mechanisms underlying many sleep disorders are still a mystery.

Sleep has mostly been investigated from the perspective of neurons, likely due to the lack of appropriate techniques to directly monitor non-neuronal cells in sleep. In the past couple of decades multiple studies have provided evidence that astrocytes, a star-shaped electrically non-excitable glial cell of the brain, as well might play a role in sleep, yet the signaling mechanisms that astrocytes employ in sleep have been mostly unknown.

The research group at University of Oslo formerly led by Professor Erlend A. Nagelhus, and now by Associate Professor Rune Enger, has demonstrated for the first time the activity patterns of astrocytes during natural sleep. One of the main signaling pathways of astrocytes are intracellular calcium increases. The team measured these calcium signals in astrocytes in the cortex of naturally sleeping mice using genetically encoded calcium indicators and in vivo two-photon microscopy. The authors found reduced calcium signaling during sleep as compared to when the mice are awake. However, there was still remaining activity during sleep which displayed different features in different sleep states.

Interestingly, astrocyte calcium activity increased upon sleep to wakefulness transitions and even preceded the neurophysiological (EEG) and behavioral (movement) signals upon waking from slow wave sleep. “This is a remarkable finding”, says shared first author Laura Bojarskaite, PhD candidate in neuroscience. “It demonstrates that astrocytes might be involved in orchestrating the waking up process”.

Such sleep-wake state specific activity suggests that astrocytes might be involved in sleep-wake state regulation. Therefore, the researchers next used a transgenic mouse line with impaired astrocyte calcium signaling and measured whether this would affect mice sleep patterns. The authors found that this manipulation disrupted slow wave sleep specifically and not rapid eye movement sleep. Mice with perturbed astrocyte calcium signaling had more microarousals (short awakenings) and shifted from one sleep state to another (slow wave sleep and intermediate state) more often, which interrupted their sleep and reduced its quality. “This means that astrocytic calcium signaling is important to maintain uninterrupted slow wave sleep and potentially to protect against waking up too often in the night”, says Bojarskaite. Interestingly, these mice also had more sleep spindles, which are signatures of particular type of neuronal activity associated with learning and memory. Too many sleep spindles are known to be associated with learning disabilities in humans and poor avoidance performance in rats.

Identifying new players involved in the regulation of slow wave sleep contributes to the understanding of the mechanisms and function of sleep as well as providing new targets for sleep disorders. One of the possible next steps for the group will be studying exactly how astrocyte calcium signals regulate slow wave sleep and sleep spindles.

Reference: Bojarskaite, L., Bjørnstad, D. M., Pettersen, K. H., Cunen, C., Hermansen, G. H., Åbjørsbråten, K. S., Chambers, A. R., Sprengel, R., Vervaeke, K., Tang, W., Enger, R., & Nagelhus, E. A. (2020). Astrocytic Ca 2+ signaling is reduced during sleep and is involved in the regulation of slow wave sleep. Nature Communications, 11(1), 3240. https://doi.org/10.1038/s41467-020-17062-2

This article has been republished from materials provided by researchers at the University of Oslo. Note: material may have been edited for length and content. For further information, please contact the cited source.