1. Cerebral mGluR5 availability contributes to elevated sleep need and behavioral adjustment after sleep deprivation
- Author
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Erich Seifritz, Paul Franken, Alfred Buck, Katharina Hefti, Mehdi Tafti, Hans-Peter Landolt, Anke Henning, Sebastian C. Holst, Milan Scheidegger, Simon M. Ametamey, Alexandra Sousek, Sohrab Saberi-Moghadam, University of Zurich, and Landolt, Hans-Peter
- Subjects
0301 basic medicine ,Mouse ,10050 Institute of Pharmacology and Toxicology ,Electroencephalography ,Gene Knockout Techniques ,Mice ,0302 clinical medicine ,2400 General Immunology and Microbiology ,Homeostasis ,Biology (General) ,fragile X syndrome ,Mice, Knockout ,medicine.diagnostic_test ,Metabotropic glutamate receptor 5 ,General Neuroscience ,2800 General Neuroscience ,Brain ,General Medicine ,Animals ,Brain/physiology ,Brain Chemistry ,Receptor, Metabotropic Glutamate 5/genetics ,Receptor, Metabotropic Glutamate 5/metabolism ,Sleep ,Sleep Deprivation ,Wakefulness ,PET-MRS ,Y-maze ,human ,molecular imaging ,mouse ,neuroscience ,plasticity marker ,working memory ,Sleep in non-human animals ,Medicine ,medicine.symptom ,Research Article ,Human ,QH301-705.5 ,Science ,Receptor, Metabotropic Glutamate 5 ,610 Medicine & health ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,1300 General Biochemistry, Genetics and Molecular Biology ,medicine ,General Immunology and Microbiology ,Working memory ,business.industry ,Sleep deprivation ,030104 developmental biology ,Metabotropic glutamate receptor ,10054 Clinic for Psychiatry, Psychotherapy, and Psychosomatics ,570 Life sciences ,biology ,business ,Neuroscience ,030217 neurology & neurosurgery - 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.
- Published
- 2017