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

Abstract

Study objectivesAstrocytes 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, whether alterations in intracellular Ca2+ concentration in astrocytes can affect sleep/wakefulness states and cortical oscillations in a brain region-dependent manner remain unclear. MethodsThe Ca2+ concentration in astrocytes was artificially increased using chemogenetics in mice. 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. ResultsThe activation of astrocytes in the hippocampus significantly decreased the total time of wakefulness and increased the total time of sleep. This had minimal effects 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. ConclusionsThese 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. Statement of SignificanceSleep is an instinctive behavior for many organisms. Recently, it has been reported that not only neurons, but also astrocytes, a type of glial cell, contribute to sleep/wakefulness states. Intracellular Ca2+ concentration, an indicator of astrocyte activity, fluctuates during sleep/wakefulness states. However, it is still unclear whether changes in Ca2+ concentration in astrocytes can affect sleep/wakefulness states. In this study, we utilized chemogenetics to activate astrocytes in mice. Our results showed that activation of astrocytes in the hippocampus causes decreased wakefulness, and that in the pons causes decreased REM sleep. Therefore, our findings demonstrate that the activation of astrocytes modulates sleep/wakefulness states in a brain region-dependent manner. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=112 SRC="FIGDIR/small/597103v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@100a766org.highwire.dtl.DTLVardef@1ee1d21org.highwire.dtl.DTLVardef@1ba8044org.highwire.dtl.DTLVardef@13af766_HPS_FORMAT_FIGEXP M_FIG C_FIG