Astrocytes influence sleep expression and regulation, but the cellular signaling pathways involved in these processes are poorly defined. We proposed that astrocytes detect and integrate a neuronal signal that accumulates during wakefulness, thereby leading to increased sleep drive. Noradrenaline (NA) satisfies several criteria for a waking signal integrated by astrocytes. We therefore investigated the role of NA signaling in astrocytes in mammalian sleep. We conditionally knocked out (cKO) β2-adrenergic receptors (β2-AR) selectively in astrocytes in mice and recorded electroencephalographic and electromyographic activity under baseline conditions and in response to sleep deprivation (SDep). cKO of astroglial β2-ARs increased active phase siesta duration under baseline conditions and reduced homeostatic compensatory changes in sleep consolidation and non-rapid eye movement slow-wave activity (SWA) after SDep. Overall, astroglial NA β2-ARs influence mammalian sleep homeostasis in a manner consistent with our proposed model of neuronal-astroglial interactions.
Keywords: adrenergic receptor; astrocyte; homeostasis; noradrenaline; siesta; sleep; sleep deprivation.