ASTROCYTIC-NEURONAL INTERACTIONS ACROSS SLEEP-WAKE STATES SHAPE HOMEOSTATIC REGULATION

Sleep is a highly conserved behavioral state that is essential for brain function, plasticity, and network stability. Cortical regions are composed of pyramidal neurons and inhibitory interneuron populations whose activity is tightly structured across vigilance states, including state-specific dynamics that support cortical plasticity during REM sleep (Aime et al., 2022). While neuronal activity across sleep and wakefulness has been extensively characterized, the role of extra-neuronal cellular elements remains less well understood. Astrocytes are increasingly recognized as active regulators of neural circuit function and important contributors to sleep regulation, yet their interactions with defined neuronal subcircuits across sleep stages remain unexplored.
Using a combination of calcium imaging approaches, including miniscope recordings and dual-color fiber photometry, together with EEG monitoring, sleep deprivation paradigms, and astrocyte-specific chemogenetic manipulation, we investigated astrocytic network dynamics across sleep and wakefulness. With this approach, we could show that astrocyte activity patterns differ between associative and sensory cortices and are selectively reshaped following sleep deprivation. Moreover, astrocytes display region-dependent dynamics that track distinct neuronal populations - namely PV and SST interneurons as well as pyramidal cells - depending on vigilance state. Together, these results underscore the importance of astrocytes as active regulators of neuronal circuit dynamics essential for sleep regulation and homeostatic adaptation, and highlight astrocyte-neuron interactions as a critical dimension for a more complete understanding of sleep function.