International Journal of Molecular Sciences Review An Extracellular Perspective on CNS Maturation: Perineuronal Nets and the Control of Plasticity Daniela Carulli 1,2,* and Joost Verhaagen 1 1 Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Royal Academy of Arts and Sciences, 1105 BA Amsterdam, The Netherlands;
[email protected] 2 Department of Neuroscience Rita Levi-Montalcini and Neuroscience Institute Cavalieri Ottolenghi, University of Turin, 10040 Turin, Italy * Correspondence:
[email protected] Abstract: During restricted time windows of postnatal life, called critical periods, neural circuits are highly plastic and are shaped by environmental stimuli. In several mammalian brain areas, from the cerebral cortex to the hippocampus and amygdala, the closure of the critical period is dependent on the formation of perineuronal nets. Perineuronal nets are a condensed form of an extracellular matrix, which surrounds the soma and proximal dendrites of subsets of neurons, enwrapping synaptic terminals. Experimentally disrupting perineuronal nets in adult animals induces the reactivation of critical period plasticity, pointing to a role of the perineuronal net as a molecular brake on plasticity as the critical period closes. Interestingly, in the adult brain, the expression of perineuronal nets is remarkably dynamic, changing its plasticity-associated conditions, including memory processes. In this review, we aimed to address how perineuronal nets contribute to the maturation of brain circuits and the regulation of adult brain plasticity and memory processes in physiological and pathological conditions. Citation: Carulli, D.; Verhaagen, J. An Extracellular Perspective on CNS Keywords: perineuronal net; critical period; chondroitin sulfate proteoglycans; learning; memory; Maturation: Perineuronal Nets and Alzheimer’s disease; drug addiction the Control of Plasticity.