Persistent cortical plasticity by upregulation of chondroitin 6-sulfation

• Published in: Nature neuroscience Vol. 15; no. 3; pp. 414 - 422
• Main Authors: Miyata, Shinji, Komatsu, Yukio, Yoshimura, Yumiko, Taya, Choji, Kitagawa, Hiroshi
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.03.2012; Nature Publishing Group
• Subjects: 631/378/2571; 631/378/2613; 631/443/376; 631/80/79/750; Action Potentials - drug effects; Action Potentials - genetics; Age Factors; Aggrecans - metabolism; Amphetamines - pharmacology; Animal Genetics and Genomics; Animals; Animals, Newborn; Astrocytes - metabolism; Bacterial Proteins - genetics; Bacterial Proteins - metabolism; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Carbohydrate Sulfotransferases; Cells, Cultured; Cerebral cortex; Chlorocebus aethiops; Chondroitin; Chondroitin Sulfate Proteoglycans - metabolism; Chondroitin Sulfates - genetics; Chondroitin Sulfates - metabolism; Electroporation - methods; Functional Laterality - physiology; Gene Expression Regulation, Developmental - genetics; Gene Expression Regulation, Developmental - physiology; Humans; In Vitro Techniques; Luminescent Proteins - genetics; Luminescent Proteins - metabolism; Mice; Mice, Transgenic; Nerve Tissue Proteins - metabolism; Neurobiology; Neuronal Plasticity - genetics; Neuronal Plasticity - physiology; Neurosciences; Otx Transcription Factors - metabolism; Parvalbumins - metabolism; Patch-Clamp Techniques; Physiological aspects; Plant Lectins - metabolism; Receptors, N-Acetylglucosamine - metabolism; Sensory Deprivation - physiology; Sulfates; Sulfotransferases - genetics; Time Factors; Up-Regulation - genetics; Up-Regulation - physiology; Vesicular Glutamate Transport Protein 2 - metabolism; Visual Cortex - cytology; Visual Cortex - drug effects; Visual Cortex - physiology; Visual Pathways - metabolism; Japan
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.3023

The authors report that a developmental increase in the 4-sulfation/6-sulfation ratio of chondroitin sulfate proteoglycans modulates the maturity of parvalbumin-expressing interneurons and leads to the termination of the critical period for ocular dominance plasticity in the mouse visual cortex. 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.