Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

Abstract

Brain cells are immersed in a complex structure forming the extracellular matrix. The composition of the matrix gradually matures during postnatal development, as the brain circuitry reaches its adult form. The fully developed extracellular environment stabilizes neuronal connectivity and decreases cortical plasticity as highlighted by the demonstration that treatments degrading the matrix are able to restore synaptic plasticity in the adult brain. The mechanisms through which the matrix inhibits cortical plasticity are not fully clarified. Here we show that a prominent component of the matrix, chondroitin sulfate proteoglycans (CSPGs), restrains morphological changes of dendritic spines in the visual cortex of adult mice. By means of in vivo and in vitro two-photon imaging and electrophysiology, we find that after enzymatic digestion of CSPGs, cortical spines become more motile and express a larger degree of structural and functional plasticity.

Enhanced cognitive flexibility in reversal learning induced by removal of the extracellular matrix in auditory cortex

“…Growing evidence supports the view that dynamic ECM changes may be involved in providing important cues for synaptic stabilization or reorganization in the adult brain (2,16). For instance, lack of components of the ECM in adult mice correlates with altered synaptic activity and plasticity (12,14,35). In our study, we have demonstrated that enzymatic ECM removal in ACx of adult Mongolian gerbils did not influence cortex-dependent learning of a new task or memory retrieval of an already established discrimination strategy.…”

“…On a more general account, our data show that the ECM might serve an important function for the regulation of stability and plasticity in learning-relevant synaptic networks. Recent findings implicate that structural changes in cortical circuits at the level of dendritic spines and individual synaptic rearrangements provide long-term information storage of prior experiences (12). On this microscopic level, the release or activation of ECM-removing or -modifying enzymes can indeed promote necessary neuronal adaptations to regulate learning-related plastic changes.…”

“…instance, by leading to increased motility of postsynaptic spines (12). Recently, we demonstrated in vitro that a decrease of the perisynaptic ECM also modulates synapses at the functional level by enhancing lateral diffusion of glutamate receptors on the neuronal surface, which impacts synaptic short-term plasticity (10).…”

“…Enzymatic degradation of the ECM in adult animals has been demonstrated to restore such forms of developmental (juvenile) plasticity with respect to topographical map plasticity in the visual cortex (4), fearresponse-mediating circuits in the amygdala (5), spinal cord injuries (6,7), and song learning circuits of zebra finches (8). In addition, enzymatic ECM removal altered several forms of synaptic plasticity in vitro and in vivo (9)(10)(11)(12). However, even though structural stability of networks acquired during developmental phases is essential for neuronal efficiency, mechanisms allowing synaptic remodeling are key events during learning and memory formation throughout life (13).…”

Simultaneous two-photon imaging of intracellular chloride concentration and pH in mouse pyramidal neurons in vivo

“…injection of urethane (1-1.5 g/kg). Craniotomy (2-to 3-mm diameter) was performed as described elsewhere, and the dura mater was removed to reduce light scattering (58). A custom-made steel head post with a central imaging chamber was glued to the skull.…”