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

Nature Neuroscience volume 14, pages 1430–1438 (2011)Cite this article

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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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Figure 1: DHPG increases rectification of AMPARs in CG4 OPCs.
Figure 2: DHPG increases single-channel conductance of AMPARs in CG4 OPCs.
Figure 3: mGluR-induced AMPAR plasticity is developmentally regulated in native OPCs.
Figure 4: ATP reduces AMPAR rectification in native OPCs.
Figure 5: TARPs are expressed in OPCs.
Figure 6: TARPs control mGluR-induced AMPAR plasticity.
Figure 7: mGluR activation increases synaptic CP-AMPARs in cerebellar NG2-positive 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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  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.

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Correspondence to Mark Farrant or Stuart G Cull-Candy.

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Zonouzi, M., Renzi, M., Farrant, M. et al. Bidirectional plasticity of calcium-permeable AMPA receptors in oligodendrocyte lineage cells. Nat Neurosci 14, 1430–1438 (2011). https://doi.org/10.1038/nn.2942

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