Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex
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Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex. / Chattopadhyaya, Bidisha; Baho, Elie; Huang, Z Josh; Schachner, Melitta; Di Cristo, Graziella.
In: J NEUROSCI, Vol. 33, No. 14, 03.04.2013, p. 5957-68.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Neural cell adhesion molecule-mediated Fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex
AU - Chattopadhyaya, Bidisha
AU - Baho, Elie
AU - Huang, Z Josh
AU - Schachner, Melitta
AU - Di Cristo, Graziella
PY - 2013/4/3
Y1 - 2013/4/3
N2 - 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.
AB - 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.
KW - Analysis of Variance
KW - Animals
KW - Animals, Newborn
KW - Cerebral Cortex
KW - Female
KW - Gene Expression Regulation, Developmental
KW - Green Fluorescent Proteins
KW - Interneurons
KW - Male
KW - Mice
KW - Mice, Transgenic
KW - Neural Cell Adhesion Molecules
KW - Neural Inhibition
KW - Organ Culture Techniques
KW - Phosphopyruvate Hydratase
KW - Protein Isoforms
KW - Proto-Oncogene Proteins c-fyn
KW - Statistics, Nonparametric
KW - Synapses
KW - gamma-Aminobutyric Acid
U2 - 10.1523/JNEUROSCI.1306-12.2013
DO - 10.1523/JNEUROSCI.1306-12.2013
M3 - SCORING: Journal article
C2 - 23554477
VL - 33
SP - 5957
EP - 5968
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 14
ER -