The Extracellular Matrix and Synapses

Extracellular matrix (ECM) molecules, derived from both neurons and glial cells, are secreted and accumulate in the extracellular space to regulate various aspects of pre- and postsynaptic differentiation, the maturation of synapses, and their plasticity. The emerging mechanisms comprise interactions of agrin, integrin ligands, and reelin, with their cognate cell-surface receptors being coupled to tyrosine kinase activities. These may induce the clustering of postsynaptic receptors and changes in their composition and function. Furthermore, direct interactions of laminins, neuronal pentraxins, and tenascin-R with voltage-gated Ca(2+) channels, alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA), and gamma-aminobutyric acid(B) (GABA(B)) receptors, respectively, shape the organization and function of different subsets of synapses. Some of these mechanisms significantly contribute to the induction of long-term potentiation in excitatory synapses, either by the regulation of Ca(2+) entry via N-methyl-D-aspartate receptors or L-type Ca(2+) channels, or by the control of GABAergic inhibition.