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Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells

Nature Neuroscience volume 14, pages 14301438 (2011) | Download Citation

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Abstract

Oligodendrocyte precursor cells (OPCs), a major glial cell type that gives rise to myelinating oligodendrocytes in the CNS, express calcium-permeable AMPA receptors (CP-AMPARs). Although CP-AMPARs are important for OPC proliferation and neuron-glia signaling, they render OPCs susceptible to ischemic damage in early development. We identified factors controlling the dynamic regulation of AMPAR subtypes in OPCs from rat optic nerve and mouse cerebellar cortex. We found that activation of group 1 mGluRs drove an increase in the proportion of CP-AMPARs, reflected by an increase in single-channel conductance and inward rectification. This plasticity required the elevation of intracellular calcium and used PI3K, PICK-1 and the JNK pathway. In white matter, neurons and astrocytes release both ATP and glutamate. Unexpectedly, activation of purinergic receptors in OPCs decreased CP-AMPAR expression, suggesting a capacity for homeostatic regulation. Finally, we found that stargazin-related transmembrane AMPAR regulatory proteins, which are critical for AMPAR surface expression in neurons, regulate CP-AMPAR plasticity in OPCs.

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  • 20 October 2011

    In the HTML version of this article initially published online, the name of one of the corresponding authors was incorrect. The error has been corrected for the HTML version of this article.

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Acknowledgements

We thank I. Coombs, C. Bats, C. Shelley, D. Soto and D. Studniarczyk for invaluable help and discussion. We are grateful to E. Molnar (Bristol University) for CG4-OPC cells, D. Attwell and C. Reynell (University College London) for providing NG2-DsRed mice, R. Nicoll (University of California, San Francisco) for TARP cDNA (rat, γ-2), J. Wood (University College London) for GFP-PICK-1 inhibitor peptide, M. Watanabe (Hokkaido University) for antibody to TARP γ-2, B. Clark (University College London) for antibody to calbindin, and D. Cutler and M. Marsh (Laboratory for Molecular Cell Biology, University College London) for generous help and access to equipment. This work was supported by a Wellcome Trust Programme grant (S.G.C.-C. and M.F.). M.Z. was in receipt of a Medical Research Council (Laboratory for Molecular Cell Biology, University College London) studentship.

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Affiliations

  1. Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

    • Marzieh Zonouzi
    • , Massimiliano Renzi
    • , Mark Farrant
    •  & Stuart G Cull-Candy

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Contributions

M.Z. performed electrophysiology and molecular experiments on cultured cells. M.R. and M.Z. performed slice recordings. M.F. and M.Z. analyzed the data. All of the authors contributed to the design and interpretation of experiments. S.G.C.-C. and M.F. supervised the project. M.Z., M.F. and S.G.C.-C. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Mark Farrant or Stuart G Cull-Candy.

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DOI

https://doi.org/10.1038/nn.2942

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