Chemogenetic activation of astrocytes modulates sleep-wakefulness states in a brain region-dependent manner.

Abstract

Study objectives: Astrocytes change their intracellular calcium (Ca²⁺) concentration during sleep/wakefulness states in mice. Furthermore, the Ca²⁺ dynamics in astrocytes vary depending on the brain region. However, it remains unclear whether alterations in astrocyte activity can affect sleep-wake states and cortical oscillations in a brain region-dependent manner.

Methods: Astrocyte activity was artificially manipulated in mice using chemogenetics. Astrocytes in the hippocampus and pons, which are 2 brain regions previously classified into different clusters based on their Ca²⁺ dynamics during sleep-wakefulness, were focused on to compare whether there are differences in the effects of astrocytes from different brain regions.

Results: The chemogenetic activation of astrocytes in the hippocampus significantly decreased the total time of wakefulness and increased the total time of sleep. This had little effect on cortical oscillations in all sleep-wakefulness states. On the other hand, the activation of astrocytes in the pons substantially suppressed rapid eye movement (REM) sleep in association with a decreased number of REM episodes, indicating strong inhibition of REM onset. Regarding cortical oscillations, the delta wave component during non-REM sleep was significantly enhanced.

Conclusions: These results suggest that astrocytes modulate sleep-wakefulness states and cortical oscillations. Furthermore, the role of astrocytes in sleep-wakefulness states appears to vary among brain regions.