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Elife. 2017 Oct 5;6. pii: e28751. doi: 10.7554/eLife.28751.

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

Author information

1
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland.
2
CRPP Sleep and Health, Zürich Center for Interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland.
3
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland.
4
Division of Nuclear Medicine, University Hospital Zürich, Zürich, Switzerland.
5
Center for Radiopharmaceutical Sciences of ETH, Zürich, Switzerland.
6
Paul Scherrer Institut, Zürich, Switzerland.
7
University Hospital of Zürich, Zürich, Switzerland.
8
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland.
9
Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland.
10
Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland.
#
Contributed equally

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.

KEYWORDS:

PET-MRS; Y-maze; fragile X syndrome; human; molecular imaging; mouse; neuroscience; plasticity marker; working memory

PMID:
28980941
PMCID:
PMC5644949
DOI:
10.7554/eLife.28751
[Indexed for MEDLINE]
Free PMC Article

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