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Brain extracellular matrix affects AMPA receptor lateral mobility and short-term synaptic plasticity


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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Figure 1: Development of ECM structures in cultured hippocampal neurons.
Figure 2: Mobility of GluR1-containing AMPA receptors labeled with antibodies to GluR1 coupled to quantum dots outside and inside of ECM structures.
Figure 3: FRAP experiments reveal different mobilities of AMPAR before and after ECM removal.
Figure 4: ECM-based surface compartments restrict AMPAR diffusion.
Figure 5: ECM removal enhances exchange between synaptic and extrasynaptic AMPARs without altering intrasynaptic mobility.
Figure 6: Synaptic short-term plasticity is altered after ECM removal.


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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.

Author information




R.F. and M.H. designed and performed all experiments and assembled a first draft of the manuscript. D.P. performed outside-out patch experiments. C.I.S., D.C. and E.D.G. formulated the working hypothesis and wrote the corresponding grant applications. All authors contributed steadily to the discussion of the actual experiments and to the writing of the manuscript.

Corresponding authors

Correspondence to Daniel Choquet or Eckart D Gundelfinger.

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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).

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