Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland; CRPP Sleep and Health, Zürich Center for Interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland
Alexandra Sousek
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland; Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
Katharina Hefti
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland
Sohrab Saberi-Moghadam
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
Alfred Buck
Division of Nuclear Medicine, University Hospital Zürich, Zürich, Switzerland
Simon M Ametamey
Center for Radiopharmaceutical Sciences of ETH, Zürich, Switzerland; Paul Scherrer Institut, Zürich, Switzerland; University Hospital of Zürich, Zürich, Switzerland
Milan Scheidegger
Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland; Institute for Biomedical Engineering, University of Zürich and ETH Zürich, Zürich, Switzerland
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland
Anke Henning
Center for Radiopharmaceutical Sciences of ETH, Zürich, Switzerland; Paul Scherrer Institut, Zürich, Switzerland; University Hospital of Zürich, Zürich, Switzerland
Erich Seifritz
CRPP Sleep and Health, Zürich Center for Interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland; Department of Psychiatry, Psychotherapy and Psychosomatics, Psychiatric Hospital, University of Zürich, Zürich, Switzerland
Center for Integrative Genomics, University of Lausanne, Lausanne, Switzerland; Department of Physiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland
Institute of Pharmacology and Toxicology, University of Zürich, Zürich, Switzerland; CRPP Sleep and Health, Zürich Center for Interdisciplinary Sleep Research, University of Zürich, Zürich, Switzerland
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.
