THE CONTRIBUTION OF THE ECM TO THE MECHANICAL PROPERTIES OF THE BRAIN AND DENDRITIC SPINE FORMATION

Neuronal plasticity, an essential mechanism underlying learning and memory, declines during adulthood. This reduction is partly mediated by the perineuronal extracellular matrix (ECM) consisting of chondroitin sulfate proteoglycans (CSPG) and hyaluronic acid, which restricts structural remodeling of synaptic contacts. ECM maturation correlates with altered brain tissue mechanics, which may contribute to reduced neuronal plasticity. The objective of this study is to investigate the contribution of the CSPG-containing ECM to the mechanical properties of the brain tissue and the impact of ECM mechanics on the formation of dendritic spines. We used atomic force microscopy and Brillouin microscopy on adult mouse brain sections to measure the stiffness of the mouse cortex in a layer-by-layer approach, considering the heterogeneity of the ECM. Additionally, the effect of ECM digestion using chondroitinase ABC, an enzyme that digests the chondroitin sulfates from the CSPGs, on the tissue mechanics were examined. Increased stiffness was found to correlate with higher ECM density, thereby underscoring the mechanical contribution of ECM. Further, we investigated the influence of OHA/GEL (oxidized hyaluronan) hydrogel stiffness on dendritic spine formation and morphology. To do so, synaptic actin intensity and dendritic protrusions of neurons were analyzed under various mechanical conditions. We observed that a softer environment is conducive to spine elongation. Together, this data suggests that CSPG-containing ECM determines the mechanical properties of the brain, which strongly impacts dendritic spine morphology.