The role of hippocampal astrocytes in sleep

Recent studies have revealed an essential contribution of cortical astrocyte calcium activity in regulation of sleep depth and state transitions (Bojarskaite et al., 2020, Nat Comms; Vaidyanathan et al., 2021, Nat Comms). However, astrocytic activity is highly heterogeneous across brain regions, and it is unclear if astrocytes mediate sleep transitions in a brain region specific manner. A region of utmost interest to investigate astrocytic activity during sleep is the hippocampus, which not only display high astrocytic heterogeneity (Viana et al., 2023, Glia), but also shows sleep-specific patterns of neuronal activity linked to complex behavioral output, such as consolidation of memories. Therefore, our aim is to investigate the activity of hippocampal astrocytes throughout the sleep-wake cycle. For this study, we used wildtype and Itpr2-/- mice that were transfected with genetically encoded calcium indicators (GCaMP6f) in the hippocampus. Additionally, these mice were equipped with a chronic hippocampal window, as well as LFP and ECoG electrodes. Hippocampal astrocytes were imaged using two-photon microscopy, together with electrophysiological recordings across the entire sleep-wake cycle, including NREM, intermediate state sleep, microarousals and REM sleep. Our findings reveal a decrease in calcium signaling during sleep compared to wakefulness in both genotypes. Calcium signals also vary across the different sleep phases and we are currently analyzing this relationship.