Cortical plasticity is most evident during a critical period in early life, but the mechanisms that restrict plasticity after the critical period are poorly understood. We found that a developmental increase in the 4-sulfation/6-sulfation (4S/6S) ratio of chondroitin sulfate proteoglycans (CSPGs), which are components of the brain extracellular matrix, leads to the termination of the critical period for ocular dominance plasticity in the mouse visual cortex. Condensation of CSPGs into perineuronal nets that enwrapped synaptic contacts on parvalbumin-expressing interneurons was prevented by cell-autonomous overexpression of chondroitin 6-sulfation, which maintains a low 4S/6S ratio. Furthermore, the increase in the 4S/6S ratio was required for the accumulation of Otx2, a homeoprotein that activates the development of parvalbumin-expressing interneurons, and for functional maturation of the electrophysiological properties of these cells. Our results indicate that the critical period for cortical plasticity is regulated by the 4S/6S ratio of CSPGs, which determines the maturation of parvalbumin-expressing interneurons.
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We thank T. Maruyama and F. Murakami for technical advises on the VEP recordings and in utero electroporation, respectively. This work was funded by a Grant-in-Aid for Scientific Research-B 21390025 (to H.K.), grants from the Scientific Research on Innovative Areas (23110003 and 23110004 to H.K. and Y.K.), and a Young Scientists grant (21890286 to S.M.) from Ministry of Education, Culture, Sports, Science & Technology, Japan.
The authors declare no competing financial interests.
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Miyata, S., Komatsu, Y., Yoshimura, Y. et al. Persistent cortical plasticity by upregulation of chondroitin 6-sulfation. Nat Neurosci 15, 414–422 (2012). https://doi.org/10.1038/nn.3023
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