Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation

Sebastian C. Holst, Alexandra Sousek, Katharina Hefti, Sohrab Saberi-Moghadam, Alfred Buck, Simon M. Ametamey, Milan Scheidegger, Paul Franken, Anke Henning, Erich Seifritz, Mehdi Tafti, Hans Peter Landolt

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Increased sleep time and intensity quantified as low-frequency brain electrical activity after sleep loss demonstrate that sleep need is homeostatically regulated, yet the underlying molecular mechanisms remain elusive. We here demonstrate that metabotropic glutamate receptors of subtype 5 (mGluR5) contribute to the molecular machinery governing sleep-wake homeostasis. Using positron emission tomography, magnetic resonance spectroscopy, and electroencephalography in humans, we find that increased mGluR5 availability after sleep loss tightly correlates with behavioral and electroencephalographic biomarkers of elevated sleep need. These changes are associated with altered cortical myo-inositol and glycine levels, suggesting sleep loss-induced modifications downstream of mGluR5 signaling. Knock-out mice without functional mGluR5 exhibit severe dysregulation of sleep-wake homeostasis, including lack of recovery sleep and impaired behavioral adjustment to a novel task after sleep deprivation. The data suggest that mGluR5 contribute to the brain’s coping mechanisms with sleep deprivation and point to a novel target to improve disturbed wakefulness and sleep.

Original languageEnglish (US)
Article numbere28751
JournaleLife
Volume6
DOIs
StatePublished - Oct 5 2017
Externally publishedYes

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Holst, S. C., Sousek, A., Hefti, K., Saberi-Moghadam, S., Buck, A., Ametamey, S. M., Scheidegger, M., Franken, P., Henning, A., Seifritz, E., Tafti, M., & Landolt, H. P. (2017). Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation. eLife, 6, [e28751]. https://doi.org/10.7554/eLife.28751.001