title: Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.
abstract: GABAergic basket interneurons form perisomatic synapses, which are essential for regulating neural networks, and their alterations are linked to various cognitive dysfunction. Maturation of basket synapses in postnatal cortex is activity dependent. In particular, activity-dependent downregulation of polysialiac acid carried by the neural cell adhesion molecule (NCAM) regulates the timing of their maturation. Whether and how NCAM per se affects GABAergic synapse development is unknown. Using single-cell genetics to knock out NCAM in individual basket interneurons in mouse cortical slice cultures, at specific developmental time periods, we found that NCAM loss during perisomatic synapse formation impairs the process of basket cell axonal branching and bouton formation. However, loss of NCAM once the synapses are already formed did not show any effect. We further show that NCAM120 and NCAM140, but not the NCAM180 isoform, rescue the phenotype. Finally, we demonstrate that a dominant-negative form of Fyn kinase mimics, whereas a constitutively active form of Fyn kinase rescues, the effects of NCAM knockdown. Altogether, our data suggest that NCAM120/NCAM140-mediated Fyn activation promotes GABAergic synapse maturation in postnatal cortex.
authors.affiliation: CHU Sainte Justine Research Center, University of Montreal, Montreal, Quebec H3T 1C5, Canada.
authors.forename: Bidisha
authors.initials: B
authors.lastname: Chattopadhyaya
authors.forename: Elie
authors.initials: E
authors.lastname: Baho
authors.forename: Z Josh
authors.initials: ZJ
authors.lastname: Huang
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
authors.forename: Graziella
authors.initials: G
authors.lastname: Di Cristo
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology; D009924:Organ Culture Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051076:Proto-Oncogene Proteins c-fyn / Q000235:genetics / Q000378:metabolism*; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D019006:Neural Cell Adhesion Molecules; D020033:Protein Isoforms; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005680:gamma-Aminobutyric Acid; C494960:Fyn protein, mouse; D051076:Proto-Oncogene Proteins c-fyn; D010751:Phosphopyruvate Hydratase
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