HIPPOCAMPAL ASTROCYTES' CONTROL OF BRAIN RHYTHMS

Cortical astrocyte calcium activity is essential in modulating sleep depth and state transitions (Bojarskaite et al., 2020, Nat Comms; Vaidyanathan et al., 2021, Nat Comms). However, due to the highly heterogeneous nature and brain-state specificity of astrocytic activity, it is unclear if astrocytic modulation of sleep transitions is reflected in other brain areas than the cortex. A region of utmost interest for investigating astrocytic activity during sleep is the hippocampus, where sleep-specific patterns of neuronal activity are linked to complex behavioral outputs such as consolidation of memories. Therefore, our aim was to quantify and modulate the calcium dynamics of hippocampal astrocytes throughout the sleep-wake cycle in mice. For this study, we used wild-type mice transfected with either genetically encoded calcium pumps (CalEx) or a calcium-activity optogenetic enhancer (Melanopsin) in the CA1 layer of the hippocampus. Mice were implanted with a chronic hippocampal imaging window and ECoG electrodes for sleep-metrics quantification, and hippocampal astrocytes were imaged using two-photon microscopy across the entire sleep-wake cycle. We categorized locomotion, wakefulness in the presence or absence of whisking, NREM, intermediate-state sleep, and REM as behavioral states. Our findings revealed a decrease in calcium signaling during sleep compared to wakefulness in both genotypes, and we introduced a new methodology for precise control of hippocampal calcium dynamics during sleep.