Matrix metalloproteinases regulate the formation of dendritic spine head protrusions during chemically induced long-term potentiation

PLoS One. 2013 May 16;8(5):e63314. doi: 10.1371/journal.pone.0063314. Print 2013.

Abstract

Dendritic spines are are small membranous protrusions that extend from neuronal dendrites and harbor the majority of excitatory synapses. Increasing evidence has shown that matrix metalloproteinases (MMPs), a family of extracellularly acting and Zn(2+)-dependent endopeptidases, are able to rapidly modulate dendritic spine morphology. Spine head protrusions (SHPs) are filopodia-like processes that extend from the dendritic spine head, representing a form of postsynaptic structural remodeling in response to altered neuronal activity. Herein, we show that chemically induced long-term potentiation (cLTP) in dissociated hippocampal cultures upregulates MMP-9 activity that controls the formation of SHPs. Blocking of MMPs activity or microtubule dynamics abolishes the emergence of SHPs. In addition, autoactive recombinant MMP-9, promotes the formation of SHPs in organotypic hippocampal slices. Furthermore, spines with SHPs gained postsynaptic α-amino-3-hydroxyl-5-methyl-4-isoxazole propionic acid (AMPA) receptors upon cLTP and the synaptic delivery of AMPA receptors was controlled by MMPs. The present results strongly imply that MMP-9 is functionally involved in the formation of SHPs and the control of postsynaptic receptor distribution upon cLTP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Dendritic Spines / metabolism*
  • Long-Term Potentiation / physiology*
  • Matrix Metalloproteinase 9 / metabolism
  • Matrix Metalloproteinases / metabolism*
  • Microtubules / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, AMPA / metabolism

Substances

  • Receptors, AMPA
  • Matrix Metalloproteinases
  • Matrix Metalloproteinase 9

Grants and funding

Research was supported by ERA-NET NEURON MODDIFSYN (J.W. and L.K.), AXREGEN grant 214003 (Z.S.), and Ministry of Science and Higher Education grant IP2011 060671 (J.W.). M.B. was partially supported by the European Regional Development Fund POIG 01.01.02.-00-008/08. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.