Extracellular matrix molecules and synaptic plasticity

Key Points In animals, organized groups of cells are surrounded by an extracellular matrix (ECM) of collagens, proteoglycans and glycoproteins. These molecules not only interact with each other, but they also activate signal transduction pathways, which coordinate cell proliferation, migration and differentiation. In addition to its roles in development and regeneration in the nervous system, the ECM is involved in physiological processes in the adult brain, such as synaptic plasticity. This review focuses on this lesser-known function of ECM molecules in the adult nervous system. Synaptic plasticity is the phenomenon by which the efficacy of synaptic transmission varies in an activity-dependent manner. A transient increase in synaptic efficacy is called short-term potentiation, whereas the persistent enhancement or reduction of synaptic strength of stimulated synapses are known as long-term potentiation (LTP) or long-term depression (LTD), respectively. Because of the complexity and diversity of synaptic plasticity mechanisms, it is not difficult to imagine that more than one ECM molecule would affect synapse formation and synaptic modifications in the adult. To identify the best candidates, this review proposes a series of criteria that need to be fulfilled to show that an ECM molecule is required for synaptic plasticity. ECM molecules that have been implicated in synaptic plasticity include laminins, reelin, heparin-binding growth-associated molecule (HB-GAM), neuronal activity-regulated pentraxin (Narp), tenascin-R, tenascin-C, and the chondroitin sulphate proteoglycans brevican and neurocan. All of the ECM molecules that have been studied so far promote LTP in the CA1 region of the hippocampus, except for HB-GAM, which inhibits it. Short-term potentiation was typically not affected after manipulation of ECM molecules, except for reelin, which increased short-term potentiation. These findings raise the question of how the effects of ECM molecules on synaptic plasticity are linked to developmental events. The sprouting of neurites that is stimulated by some of these molecules could promote the formation of new synapses, but it is equally conceivable that the barrier functions of certain ECM molecules are required for stabilization of nascent contacts. Interactions between cells and the extracellular matrix (ECM) have long been accepted to have pivotal roles in neural development and regeneration. Recent data also support the involvement of several ECM m