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

Publication ,  Journal Article
Chattopadhyaya, B; Baho, E; Huang, ZJ; Schachner, M; Di Cristo, G
Published in: J Neurosci
April 3, 2013

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.

Duke Scholars

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

April 3, 2013

Volume

33

Issue

14

Start / End Page

5957 / 5968

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Statistics, Nonparametric
  • Proto-Oncogene Proteins c-fyn
  • Protein Isoforms
  • Phosphopyruvate Hydratase
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Neural Cell Adhesion Molecules
 

Citation

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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. J Neurosci, 33(14), 5957–5968. https://doi.org/10.1523/JNEUROSCI.1306-12.2013
Chattopadhyaya, Bidisha, Elie Baho, Z Josh Huang, Melitta Schachner, and Graziella Di Cristo. “Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.J Neurosci 33, no. 14 (April 3, 2013): 5957–68. https://doi.org/10.1523/JNEUROSCI.1306-12.2013.
Chattopadhyaya B, Baho E, Huang ZJ, Schachner M, Di Cristo G. Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex. J Neurosci. 2013 Apr 3;33(14):5957–68.
Chattopadhyaya, Bidisha, et al. “Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.J Neurosci, vol. 33, no. 14, Apr. 2013, pp. 5957–68. Pubmed, doi:10.1523/JNEUROSCI.1306-12.2013.
Chattopadhyaya B, Baho E, Huang ZJ, Schachner M, Di Cristo G. Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex. J Neurosci. 2013 Apr 3;33(14):5957–5968.

Published In

J Neurosci

DOI

EISSN

1529-2401

Publication Date

April 3, 2013

Volume

33

Issue

14

Start / End Page

5957 / 5968

Location

United States

Related Subject Headings

  • gamma-Aminobutyric Acid
  • Synapses
  • Statistics, Nonparametric
  • Proto-Oncogene Proteins c-fyn
  • Protein Isoforms
  • Phosphopyruvate Hydratase
  • Organ Culture Techniques
  • Neurology & Neurosurgery
  • Neural Inhibition
  • Neural Cell Adhesion Molecules