Many synapses in the mature CNS are wrapped by a dense extracellular matrix (ECM). Using single-particle tracking and fluorescence recovery after photobleaching, we found that this net-like ECM formed surface compartments on rat primary neurons that acted as lateral diffusion barriers for AMPA-type glutamate receptors. Enzymatic removal of the ECM increased extrasynaptic receptor diffusion and the exchange of synaptic AMPA receptors. Whole-cell patch-clamp recording revealed an increased paired-pulse ratio as a functional consequence of ECM removal. These results suggest that the surface compartments formed by the ECM hinder lateral diffusion of AMPA receptors and may therefore modulate short-term synaptic plasticity.
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We thank C. Poujol and P. Legros for help with video microscopy, C. Breillat, B. Tessier and D. Bouchet for expert technical assistence, J. Falk for NrCAM and GPI-GFP constructs, M. Carta and P. Opazo for support with the slice cultures, O. Kobler for help with three-dimensional image processing, and A. Triller and A. Fejtová for very helpful discussions. This work was supported by grants from the Centre National de la Recherche Scientifique, the Conseil Régional d'Aquitaine, the Ministère de la Recherche, the Fondation pour la Recherche Médicale, the European Commission (CT-2005-005320), the Deutsche Forschungsgemeinschaft (GU230/5-2/5-3), a Max Planck award from the A.v. Humboldt Foundation and the Max Planck Society. During part of the work, R.F. was supported by a fellowship from the Swiss National Fonds.
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Frischknecht, R., Heine, M., Perrais, D. et al. Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity. Nat Neurosci 12, 897–904 (2009). https://doi.org/10.1038/nn.2338
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