Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex.
J Neurosci
; 33(14): 5957-68, 2013 Apr 03.
Article
en En
| MEDLINE
| ID: mdl-23554477
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.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Sinapsis
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Corteza Cerebral
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Moléculas de Adhesión de Célula Nerviosa
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Proteínas Proto-Oncogénicas c-fyn
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Ácido gamma-Aminobutírico
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Interneuronas
Límite:
Animals
Idioma:
En
Revista:
J Neurosci
Año:
2013
Tipo del documento:
Article
País de afiliación:
Canadá