Chondroitin 4-O-sulfation regulates hippocampal perineuronal nets and synaptic plasticity

Perineuronal nets (PNNs) are specialized, lattice-like extracellular matrix (ECM) structures that condense around subpopulations of neurons and control critical periods of brain plasticity. Chondroitin sulfate proteoglycans (CSPGs) are major structural components of PNNs, and the sulfation patterns found on their glycan chains change dynamically throughout development into adulthood. We generated a brain-specific knockout of the chondroitin 4-O-sulfotransferase gene Chst11 to investigate the role of 4-O-sulfated CS motifs that predominate in adulthood. We found that CS 4-O-sulfation regulates PNN density, synapse formation, and hippocampal cognitive functions. CS 4-O-sulfation may therefore represent a novel target for the modulation of synaptic plasticity and study of neurodegenerative and psychiatric disorders.