Astrocytic modulation of sleep homeostasis and cognitive consequences of sleep loss.
Astrocytes modulate neuronal activity by releasing chemical transmitters via a process termed gliotransmission. The role of this process in the control of behavior is unknown. Since one outcome of SNARE-dependent gliotransmission is the regulation of extracellular adenosine and because adenosine promotes sleep, we genetically inhibited the release of gliotransmitters and asked if astrocytes play an unsuspected role in sleep regulation. Inhibiting gliotransmission attenuated the accumulation of sleep pressure, assessed by measuring the slow wave activity of the EEG during NREM sleep, and prevented cognitive deficits associated with sleep loss. Since the sleep-suppressing effects of the A1 receptor antagonist CPT were prevented following inhibition of gliotransmission and because intracerebroventricular delivery of CPT to wild-type mice mimicked the transgenic phenotype, we conclude that astrocytes modulate the accumulation of sleep pressure and its cognitive consequences through a pathway involving A1 receptors.
Halassa
Michael M
MM
Department of Neuroscience, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
Florian
Cedrick
C
Fellin
Tommaso
T
Munoz
James R
JR
Lee
So-Young
SY
Abel
Ted
T
Haydon
Philip G
PG
Frank
Marcos G
MG
D000241:Adenosine / Q000378:metabolism*; D058916:Adenosine A1 Receptor Antagonists; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002450:Cell Communication / Q000502:physiology; D003072:Cognition Disorders / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D049452:Green Fluorescent Proteins / Q000235:genetics; D006706:Homeostasis / Q000502:physiology; D007276:Injections, Intraventricular; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D043682:Receptor, Adenosine A1 / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D019076:Transgenes
D058916:Adenosine A1 Receptor Antagonists; D043682:Receptor, Adenosine A1; D050600:SNARE Proteins; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D000241:Adenosine