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Elife. 2017 Jun 13;6. pii: e28080. doi: 10.7554/eLife.28080.

Signalling through AMPA receptors on oligodendrocyte precursors promotes myelination by enhancing oligodendrocyte survival.

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Wolfson Institute for Biomedical Research, University College London, London, United Kingdom.
Department of Neuroscience, Physiology and Pharmacology, University College London, London, United Kingdom.
The Center for Electron Microscopy and Bio-Imaging Research and Department of Physiology, Iwate Medical University, Morioka, Japan.
Max-Planck Research Group at the Institute for Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany.
Department of Clinical Neurobiology, Deutches Krebforschungzentrum, University of Heidelberg, Heidelberg, Germany.


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.


AMPA receptor; conditional knockout; developmental biology; glutamate; internode length; mouse; neuroscience; oligodendrocyte; stem cells; survival

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