Neural cell adhesion molecule-mediated fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex

Chattopadhyaya, B., Baho, E., Huang, Z. J., Schachner, M., Di Cristo, G. (2013) Neural cell adhesion molecule-mediated fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex. Journal of Neuroscience, 33 (14). pp. 5957-68. ISSN 0270-6474

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URL: http://www.ncbi.nlm.nih.gov/pubmed/23554477
DOI: 10.1523/JNEUROSCI.1306-12.2013

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > small molecules > GABA
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neocortical interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neocortical interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neocortical interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neocortical interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neocortical interneurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > neocortical interneurons

organs, tissues, organelles, cell types and functions > tissues types and functions > cerebral cortex
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > tissues types and functions > neural networks
bioinformatics > genomics and proteomics > small molecules
organs, tissues, organelles, cell types and functions > sub-cellular tissues: types and functions > synapse
CSHL Authors:
Communities: CSHL labs > Huang lab
Depositing User: Matt Covey
Date Deposited: 22 May 2013 19:09
Last Modified: 22 May 2013 19:09
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28307

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