Synaptically released matrix metalloproteinase activity in control of structural plasticity and the cell surface distribution of GluA1-AMPA receptors

PLoS One. 2014 May 22;9(5):e98274. doi: 10.1371/journal.pone.0098274. eCollection 2014.


Synapses are particularly prone to dynamic alterations and thus play a major role in neuronal plasticity. Dynamic excitatory synapses are located at the membranous neuronal protrusions called dendritic spines. The ability to change synaptic connections involves both alterations at the morphological level and changes in postsynaptic receptor composition. We report that endogenous matrix metalloproteinase (MMP) activity promotes the structural and functional plasticity of local synapses by its effect on glutamate receptor mobility and content. We used live imaging of cultured hippocampal neurons and quantitative morphological analysis to show that chemical long-term potentiation (cLTP) induces the permanent enlargement of a subset of small dendritic spines in an MMP-dependent manner. We also used a superresolution microscopy approach and found that spine expansion induced by cLTP was accompanied by MMP-dependent immobilization and synaptic accumulation as well as the clustering of GluA1-containing AMPA receptors. Altogether, our results reveal novel molecular and cellular mechanisms of synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Animals
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Humans
  • Matrix Metalloproteinases / metabolism*
  • Neuronal Plasticity*
  • Rats, Wistar
  • Receptors, AMPA / metabolism*
  • Synapses / enzymology*


  • Receptors, AMPA
  • Matrix Metalloproteinases
  • glutamate receptor ionotropic, AMPA 1

Grants and funding

Research was supported by ERA-NET NEURON MODDIFSYN and the National Science Centre (Dec-2011/01/D/NZ3/00163). This work was partially supported by EU FP7 Project, GA No 264173 (Bio-Imagine). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.