Michael Halassa, Ph.D.

Department of Neuroscience
University of Pennsylvania

"Astrocytic Adenosine Controls Mammalian Sleep Homeostasis."

Astrocytes are known to modulate synaptic transmission and neuronal activity by the release of chemical transmitters in a process termed gliotransmission. However, the roles of gliotransmission in the control of mammalian behavior are not known. Since SNARE-dependent gliotransmission is known to regulate extracellular adenosine and adenosine exerts sleep promoting effects, we used a conditional genetic system to inhibit gliotransmission to determine if astrocytes play an unsuspected role in sleep regulation. Following sleep deprivation, there is a compensatory increase in total sleep time and sleep continuity that we demonstrate are prevented by the inhibition of gliotransmission. Inhibition of gliotransmission attenuated A1 receptor-dependent inhibition of cortical synaptic transmission and selectively blocked the sleep-suppressing effects of the A1 receptor antagonist CPT. Chronic in vivo administration of CPT to wildtype mice mimicked the transgenic phenotype by preventing the homeostatic response to sleep deprivation. This study provides the first evidence that astrocytes and gliotransmission play an essential role in a complex mammalian behavior, and we identify glial-dependent A1 receptor activation as a critical pathway underlying the effects of sleep deprivation.