Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait

Guangsen Shi; Chen Yin; Zenghua Fan; Lijuan Xing; Yulia Mostovoy; Pui-Yan Kwok; Liza H Ashbrook; Andrew D Krystal; Louis J Ptáček; Ying-Hui Fu

doi:10.1016/j.cub.2020.09.071

Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait

Curr Biol. 2021 Jan 11;31(1):13-24.e4. doi: 10.1016/j.cub.2020.09.071. Epub 2020 Oct 15.

Authors

Affiliations

¹ Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA.
² Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA.
³ Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143, USA; Department of Dermatology, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA.
⁴ Department of Psychiatry, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA.
⁵ Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: ljp@ucsf.edu.
⁶ Department of Neurology, University of California, San Francisco, San Francisco, CA 94143, USA; Institute for Human Genetics, University of California, San Francisco, San Francisco, CA 94143, USA; Weill Institute for Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA 94143, USA. Electronic address: ying-hui.fu@ucsf.edu.

PMID: 33065013
DOI: 10.1016/j.cub.2020.09.071

Abstract

Sufficient and efficient sleep is crucial for our health. Natural short sleepers can sleep significantly shorter than the average population without a desire for more sleep and without any obvious negative health consequences. In searching for genetic variants underlying the short sleep trait, we found two different mutations in the same gene (metabotropic glutamate receptor 1) from two independent natural short sleep families. In vitro, both of the mutations exhibited loss of function in receptor-mediated signaling. In vivo, the mice carrying the individual mutations both demonstrated short sleep behavior. In brain slices, both of the mutations changed the electrical properties and increased excitatory synaptic transmission. These results highlight the important role of metabotropic glutamate receptor 1 in modulating sleep duration.

Keywords: loss-of-function; mGluR1; short-sleep.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Animals
DNA Mutational Analysis
Excitatory Postsynaptic Potentials / physiology
Exome Sequencing
Female
Hippocampus / physiology
Humans
Male
Mice
Mice, Transgenic
Models, Animal
Mutation
Neuronal Plasticity / physiology
Patch-Clamp Techniques
Pedigree
Polysomnography
Receptors, Metabotropic Glutamate / genetics*
Receptors, Metabotropic Glutamate / metabolism
Sleep / genetics*
Time Factors

Substances

GRM1 protein, human
Receptors, Metabotropic Glutamate
metabotropic glutamate receptor type 1

Abstract

Publication types

MeSH terms

Substances

Grants and funding