Polysialic acid (PSA) fulfills several criteria for a molecule involved in structural plasticity, including expression in regions capable of plasticity, re-expression in structures undergoing synaptic rearrangement in the adult, downregulation following innervation, and regulation by activity. In addition, removal of PSA reduces the capacity for structural plasticity. PSA may be paradigmatic for other large polymeric carbohydrates, such as glycosaminoglycans and proteoglycans, which also are highly charged and can be extensively hydrated. These carbohydrates may affect structural plasticity by altering cell-cell and/or cell-matrix interactions by increasing intermolecular spacing through hydration.