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Neuron. 2017 Sep 13;95(6):1365-1380.e5. doi: 10.1016/j.neuron.2017.08.022. Epub 2017 Aug 31.

Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle.

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Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA; Inserm, Laboratory of Development and Plasticity of the Neuroendocrine Brain, Jean-Pierre Aubert Research Center, U1172, Lille, France; University of Lille, FHU 1000 days for Health, School of Medicine, Lille, France. Electronic address:
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, USA.
Robert Stone Dow Neurobiology Laboratories, Legacy Research Institute, Portland, OR, USA.
Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA. Electronic address:


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.


EEG; astrocytic metabolic networks; gap junction; lactate; orexin neuron; sleep-wake cycle

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