The role of ECM molecules in activity‐dependent synaptic development and plasticity

Abstract

Growth and guidance of neurites (axons and dendrites) during development is the prerequisite for the establishment of functional neural networks in the adult organism. In the adult, mechanisms similar to those used during development may regulate plastic changes that underlie important nervous system functions, such as memory and learning. There is now ever-increasing evidence that extracellular matrix (ECM)-associated factors are critically involved in the formation of neuronal connections during development, and their plastic changes in the adult. Here, we review the current literature on the role of ECM components in activity-dependent synaptic development and plasticity, with the major focus on the thrombospondin type I repeat (TSR) domain-containing proteins. We propose that ECM components may modulate neuronal development and plasticity by: 1) regulating cellular motility and morphology, thus contributing to structural alterations that are associated with the expression of synaptic plasticity, 2) coordinating transsynaptic signaling during plasticity via their cell surface receptors, and 3) defining the physical parameters of the extracellular space, thereby regulating diffusion of soluble signaling molecules in the extracellular space (ECS).

Plasticity of perisynaptic astroglia during synaptogenesis in the mature rat hippocampus

“…Here we demonstrate astroglia-free microdomains through which new filopodia might emerge to form synapses without contacting astroglial processes (Fiala et al, 1998;Harris et al, 1992). Regulation of the composition of the extracellular matrix, through secretion of proteases or reduced secretion of protease inhibitors from astroglia, might also be important to provide an unobstructed path for new spine outgrowth (Giau et al, 2005;Pavlov et al, 2004). Ongoing maintenance of these astroglia-free microdomains could be important for synaptic plasticity in the mature hippocampus.…”

Anterograde Jelly belly ligand to Alk receptor signaling at developing synapses is regulated by Mind the gap

“…Secreted trans-synaptic signaling ligands necessarily transverse and interact within the extracellular matrix (ECM), a complex milieu of secreted glycoproteins, proteoglycans and growth factors located within the synaptic cleft and adjacent perisynaptic domains (Dityatev and Schachner, 2003;Pavlov et al, 2004;Dityatev and Schachner, 2006). For example, the delivery of presynaptically secreted Wg and Wg-binding Evenness interrupted (Evi; Wntless -FlyBase) protein to postsynaptic Fz2 receptors occurs via large exosomes extruded through the cleft ECM domain (Korkut et al, 2009).…”

Mechanisms of Action and Persistent Neuroplasticity by Drugs of Abuse

“…The extracellular matrix (ECM) network is an active participant in brain function and neuroplasticity (reviewed in Pavlov et al, 2004). The ECM consists of various molecules (glycoproteins and proteoglycans) secreted by all cells that are assembled inside this matrix (Bosman and Stamenkovic, 2003).…”

“…ECM network regulates synaptogenesis, consolidation, strengthening, and maintenance of synapses (Fields and Itoh, 1996). During development, ECM participates in neuronal differentiation, neuronal movement, guidance for growing axons, and synaptogenesis (Pavlov et al, 2004). In the mature brain, ECM is crucial not only for anchoring of neurons and organization of brain regions (structural function) but also for transducing a wide range of signals to the neurons (Thalhammer and Cingolani, 2014).…”