Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival
- University College London, United Kingdom
- Iwate Medical University, Japan
- University of Heidelberg, Germany
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
William D Richardson
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).
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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Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival
eLife 6:e28080.
https://doi.org/10.7554/eLife.28080
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