Abstract
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.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Action Potentials / drug effects
-
Action Potentials / genetics
-
Age Factors
-
Aggrecans / metabolism
-
Amphetamines / pharmacology
-
Animals
-
Animals, Newborn
-
Astrocytes / metabolism
-
Bacterial Proteins / genetics
-
Bacterial Proteins / metabolism
-
Carbohydrate Sulfotransferases
-
Cells, Cultured
-
Chlorocebus aethiops
-
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
-
Neuronal Plasticity / genetics
-
Neuronal Plasticity / physiology*
-
Otx Transcription Factors / metabolism
-
Parvalbumins / metabolism
-
Patch-Clamp Techniques
-
Plant Lectins / metabolism
-
Receptors, N-Acetylglucosamine / metabolism
-
Sensory Deprivation / physiology
-
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
Substances
-
Aggrecans
-
Amphetamines
-
Bacterial Proteins
-
Chondroitin Sulfate Proteoglycans
-
Luminescent Proteins
-
N-methyl-N-propyl amphetamine
-
Nerve Tissue Proteins
-
Otx Transcription Factors
-
Otx2 protein, mouse
-
Parvalbumins
-
Plant Lectins
-
Receptors, N-Acetylglucosamine
-
Vesicular Glutamate Transport Protein 2
-
wisteria lectin
-
yellow fluorescent protein, Bacteria
-
Chondroitin Sulfates
-
Sulfotransferases