Critical Periods and Beyond: Dynamic Functions of Perineuronal Nets in Cognition, Development, and Disease

First discovered by Golgi, perineuronal nets (PNNs) are extracellular matrices that surround various neuron types in the nervous system. They have been found to emerge at the end of developmental critical periods and serve as “molecular brakes” on plasticity. Perineuronal nets have traditionally been studied in the context of sensory and cognitive plasticity, but recent studies extend their contributions to brain plasticity involved in substance use disorders, metabolism, neurodegeneration, and more. This review will summarize recent discoveries about the functions of PNNs across diverse circuits, contexts, and species, across different stages of life, and between disease and nondisease states and will integrate fundamental and clinical studies to identify conserved and novel functions of PNNs. Given the recent map of extensive PNN expression, we hope to encourage investigators researching diverse neural systems to examine PNN contributions to circuit function and behavior.