Journal
NEURON
Volume 95, Issue 6, Pages 1365-+Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2017.08.022
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Funding
- NIH [R01 NS037585, R01 AA020183]
- Epilepsy Foundation
- Marie Sklodowska-Curie Actions-European Research Fellowship (H2020-MSCA-IF) [ID656657]
- Region Hauts-de-France (program VisionAIRR)
- NIH/NINDS [R01NS092466, R01NS092786]
- NINDS [R01 NS084920]
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Astrocytes produce and supply metabolic substrates to neurons through gap junction-mediated astroglial networks. However, the role of astroglial metabolic networks in behavior is unclear. Here, we demonstrate that perturbation of astroglial networks impairs the sleep-wake cycle. Using a conditional Cre-Lox system in mice, we show that knockout of the gap junction subunit connexin 43 in astrocytes throughout the brain causes excessive sleepiness and fragmented wakefulness during the nocturnal active phase. This astrocyte-specific genetic manipulation silenced the wake-promoting orexin neurons located in the lateral hypothalamic area (LHA) by impairing glucose and lactate trafficking through astrocytic networks. This global wakefulness instability was mimicked with viral delivery of Cre recombinase to astrocytes in the LHA and rescued by in vivo injections of lactate. Our findings propose a novel regulatory mechanism critical for maintaining normal daily cycle of wakefulness and involving astrocyte-neuron metabolic interactions.
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