Cortical astrocytes independently regulate sleep depth and duration via separate GPCR pathways

Non-rapid eye movement (NREM) sleep, characterized by slow-wave electrophysiological activity, underlies several critical functions, including learning and memory. However, NREM sleep is heterogeneous, varying in duration, depth, and spatially across the cortex. While these NREM sleep features are thought to be largely independently regulated, there is also evidence that they are mechanistically coupled. To investigate how cortical NREM sleep features are controlled, we examined the astrocytic network, comprising a cortex-wide syncytium that influences population-level neuronal activity. We quantified endogenous astrocyte activity in mice over natural sleep and wake, then manipulated specific astrocytic G-protein-coupled receptor (GPCR) signaling pathways in vivo. We find that astrocytic Gi- and Gq-coupled GPCR signaling separately control NREM sleep depth and duration, respectively, and that astrocytic signaling causes differential changes in local and remote cortex. These data support a model in which the cortical astrocyte network serves as a hub for regulating distinct NREM sleep features.

Methods
Adult mice were injected with viruses to express the Ca2+ indicator GCaMP6f in cortical astrocytes and/or the Gi- or Gq-DREADD in cortical astrocytes. Mice were also implanted with LFP, EEG, and EMG electrodes. In all experiments, simultaneous electrophysiology and 2-photon imaging was performed. Data provided here include raw electrophysiology data for each recording in all experiments (“ephysData”). Additionally, astrocyte Ca2+ data is provided (“aquaData”) that has been processed using the event detection software, Astrocyte Quantitative Analysis (AQuA, Wang et al., 2019).