Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation
- University of Zürich, Switzerland
- University of Lausanne, Switzerland
- University Hospital Zürich, Switzerland
- Swiss Federal Institute of Technology, Switzerland
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.
Article and author information
Author details
Hans-Peter Landolt
Funding
Swiss National Science Foundation (320030_135414)
- Hans-Peter Landolt
Universität Zürich (Sleep & Health)
- Hans-Peter Landolt
NCCR Neural Plasticity and Repair
- Erich Seifritz
- Hans-Peter Landolt
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: All animal experiments were carried out in accordance with the regulations of the Swiss Federal and State of Vaud Veterinary Offices (No. 2699.0).
Human subjects: All experimental procedures were conducted in accordance with the declaration of Helsinki (1964) and approved by the cantonal (ethics committee for research on human subjects of the canon of Zurich [Reference Nr. EK-Nr. 786] and Swiss federal authorities for research on human (Swiss Federal Institute of Public Health, Reference Nr. 464-0002-6/08.005701) subjects.
Copyright
© 2017, Holst et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation
eLife 6:e28751.
https://doi.org/10.7554/eLife.28751
