Astrocytes at the heart of sleep: from genes to network dynamics.

Astrocytes have transcended their role from mere structural scaffolds to pivotal regulators of neural circuitry and sleep-wake dynamics. The strategic proximity of their fine processes to blood vessels and synapses positions them as key players in neurobiology, contributing to the tripartite synapse concept. Gap-junction proteins also enable astrocytes to form an extensive network interacting with neuronal assemblies to influence sleep physiology. Recent advances in genetic engineering, neuroimaging and molecular biology have deepened our understanding of astrocytic functions. This review highlights the different mechanisms by which astrocytes regulate sleep, notably through transcriptomic and morphological changes, as well as gliotransmission, whereby intracellular calcium (Ca) dynamics plays a significant role in modulating the sleep-wake cycle. In vivo optogenetic stimulation of astrocytes indeed induces ATP release, which is subsequently degraded into adenosine, modulating neuronal excitability in sleep-wake regulatory brain regions. Astrocytes also participate in synaptic plasticity, potentially modulating sleep-associated downscaling, a process essential for memory consolidation and preventing synaptic saturation. Although astrocytic involvement in synaptic maintenance is well supported, the precise molecular mechanisms linking these processes to sleep regulation remain to be elucidated. By highlighting astrocytes' multiple roles in sleep physiology, these insights deepen our understanding of sleep mechanisms and pave the way for improving sleep quality.