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Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum

Abstract

We found that demyelinated axons formed functional glutamatergic synapses onto adult-born NG2+ oligodendrocyte progenitor cells (OPCs) migrating from the subventricular zone after focal demyelination of adult mice corpus callosum. This glutamatergic input was substantially reduced compared with endogenous callosal OPCs 1 week after lesion and was lost on differentiation into oligodendrocytes. Therefore, axon–oligodendrocyte progenitor synapse formation is a transient and regulated step that occurs during remyelination of callosal axons.

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Figure 1: Adult-born SVZ NG2-positive cells display synaptic currents after migrating into a demyelinated lesion of the corpus callosum.
Figure 2: Synaptically connected SVZ-derived OPCs give rise to oligodendrocytes.
Figure 3: Glutamatergic synaptic transmission between axons and NG2-positive cells is reduced 1 week after demyelination.

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Acknowledgements

We thank F. Gage (Salk Institute) and J. Goldman (Columbia University) for the pNIT-GFP retrovirus, A. Nishiyama (University of Connecticut) for the NG2-dsRed mouse and D. Rowitch (University of California San Francisco) for antibody to Olig2. We are particularly grateful to J. Corbin for discussion and to R. McCarter for help with statistical analysis. This work was supported by grants from the US National Institutes of Health (R01NS045702 and R01NS045702 to V.G., K99NS057944 to A.A. and Intellectual and Developmental Disabilities Research Center P30HD40677). A.E. was supported by a Postdoctoral Fellowship from the Department of Education and Science of the Spanish Government.

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A.E. and J.-M.M. designed, performed and analyzed all of the experiments. A.A. helped with the LPC injection experiments and with the preparation of the retrovirus. V.G. designed the experiments with A.E. and J.-M.M. supervised the project and wrote the manuscript with A.E. and J.-M.M.

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Correspondence to Vittorio Gallo.

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The authors declare no competing financial interests.

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Supplementary Figures 1–6 and Supplementary Methods (PDF 2713 kb)

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Etxeberria, A., Mangin, JM., Aguirre, A. et al. Adult-born SVZ progenitors receive transient synapses during remyelination in corpus callosum. Nat Neurosci 13, 287–289 (2010). https://doi.org/10.1038/nn.2500

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