1. Developmental Biology
  2. Neuroscience
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Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival

  1. Eleni Kougioumtzidou
  2. Takahiro Shimizu
  3. Nicola B Hamilton
  4. Koujiro Tohyama
  5. Rolf Sprengel
  6. Hannah Monyer
  7. David Attwell  Is a corresponding author
  8. William D Richardson  Is a corresponding author
  1. University College London, United Kingdom
  2. Iwate Medical University, Japan
  3. University of Heidelberg, Germany
Research Article
  • Cited 51
  • Views 2,894
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Cite this article as: eLife 2017;6:e28080 doi: 10.7554/eLife.28080

Abstract

Myelin, made by oligodendrocytes, is essential for rapid information transfer in the central nervous system. Oligodendrocyte precursors (OPs) receive glutamatergic synaptic input from axons but how this affects their development is unclear. Murine OPs in white matter express AMPA receptor (AMPAR) subunits GluA2, GluA3 and GluA4. We generated mice in which OPs lack both GluA2 and GluA3, or all three subunits GluA2/3/4, which respectively reduced or abolished AMPAR-mediated input to OPs. In both double- and triple-knockouts OP proliferation and number were unchanged but ~25% fewer oligodendrocytes survived in the subcortical white matter during development. In triple knockouts, this shortfall persisted into adulthood. The oligodendrocyte deficit resulted in ~20% fewer myelin sheaths but the average length, number and thickness of myelin internodes made by individual oligodendrocytes appeared normal. Thus, AMPAR-mediated signalling from active axons stimulates myelin production in developing white matter by enhancing oligodendrocyte survival, without influencing myelin synthesis per se.

Article and author information

Author details

  1. Eleni Kougioumtzidou

    Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. Takahiro Shimizu

    Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  3. Nicola B Hamilton

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Koujiro Tohyama

    The Center for Electron Microscopy and Bio-Imaging Research, Iwate Medical University, Morioka, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Rolf Sprengel

    Institute for Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Hannah Monyer

    Department of Clinical Neurobiology, University of Heidelberg, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. David Attwell

    Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom
    For correspondence
    d.attwell@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3618-0843
  8. William D Richardson

    Wolfson Institute for Biomedical Research, University College London, London, United Kingdom
    For correspondence
    w.richardson@ucl.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7261-2485

Funding

Wellcome (100269/Z/12/Z)

  • William D Richardson

Japan Society for the Promotion of Science (24650181)

  • Koujiro Tohyama

Wellcome (108726/Z/15/Z)

  • William D Richardson

Wellcome (099222/Z/12/Z)

  • David Attwell

Wellcome (089591/Z/09/Z)

  • Eleni Kougioumtzidou

European Research Council (293544)

  • William D Richardson

German Research Foundation (SFB636/A4)

  • Rolf Sprengel

German Research Foundation (SFB1134/B01)

  • Rolf Sprengel

German Research Foundation (SFB 1158/A05)

  • Rolf Sprengel

Japan Society for the Promotion of Science (25245069)

  • Koujiro Tohyama

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 pre-approved by the UCL Ethical Committee and authorized by the Home Office of the UK Government in accordance with Animals (Scientific Procedures) Act 1986., under Project Licences PPL 70/7299 and PPL 70/8976 (D. Attwell) and PPL 70/7614 (W.D. Richardson).

Reviewing Editor

  1. Carol A Mason, Columbia University, United States

Publication history

  1. Received: April 25, 2017
  2. Accepted: June 7, 2017
  3. Accepted Manuscript published: June 13, 2017 (version 1)
  4. Version of Record published: June 26, 2017 (version 2)

Copyright

© 2017, Kougioumtzidou 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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