Connexin 43-Mediated Astroglial Metabolic Networks Contribute to the Regulation of the Sleep-Wake Cycle
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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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At the syncytium scale, groups of astrocytes form functional domains via gap-junction connectivity that match neuronal activity domains and may coordinate excitability and support energetic demands of functional neuronal ensembles.
“third, a syncytium scale, at which groups of astrocytes form, via dynamic gap-junction connectivity, functional domains matching domains of neuronal activity and may coordinate the excitability and support the energetic demands of the functional neuronal ensembles 40, 79”
From Astrocyte function from information processing to cognition and cognitive impairment (2019) · cites this paper as [40]
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Self-citation
- Authors
- Clasadonte, J., Scemes, E., Wang, Z., Boison, D., & Haydon, P. G.
- Affiliations
- Albert Einstein College of Medicine (US)
- Legacy Health (US)
- Tufts University (US)
- Corresponding author
- Haydon, Philip G.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 95
- Issue
- 6
- Pages
- 1365-1380.e5
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC5617118
- OpenAlex
- W2752703006
- Cited by
- 200
- References
- 70
- Citations by year
- 2026: 18 · 2025: 14 · 2024: 20 · 2023: 23 · 2022: 29 · 2021: 27 · 2020: 23 · 2019: 20 · 2018: 24 · 2017: 2
- FWCI
- 10.83
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Rutgers University Community Repository (Rutgers University) (submittedVersion)
- Funders
- NIH
- Epilepsy Foundation
- Marie Skłodowska-Curie Actions—European Research Fellowship (H2020-MSCA-IF-2014, ID656657)
- Région Hauts-de-France
- VisionAIRR
- NIH/NINDS (R01NS092466, R01NS092786)
- NINDS (R01 NS084920)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Connexins and lens biology
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- connexin 43, astrocytes, sleep-wake cycle, gap junctions, orexin neurons, lateral hypothalamus, excessive sleepiness, wakefulness
- MeSH terms
- Orexins, Animals, Astrocytes, Glucose, Hypothalamic Area, Lateral, Neurons, Sleep, Wakefulness, Gap Junctions, Connexin 43, Mice, Knockout, Lactic Acid, Mice
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