PT  - JOURNAL ARTICLE
AU  - Galina P. Demyanenko
AU  - Vishwa Mohan
AU  - Xuying Zhang
AU  - Leann H. Brennaman
AU  - Katherine E.S. Dharbal
AU  - Tracy S. Tran
AU  - Paul B. Manis
AU  - Patricia F. Maness
TI  - Neural Cell Adhesion Molecule NrCAM Regulates Semaphorin 3F-Induced Dendritic Spine Remodeling
AID  - 10.1523/JNEUROSCI.1774-14.2014
DP  - 2014 Aug 20
TA  - The Journal of Neuroscience
PG  - 11274--11287
VI  - 34
IP  - 34
4099  - http://www.jneurosci.org/content/34/34/11274.short
4100  - http://www.jneurosci.org/content/34/34/11274.full
SO  - J. Neurosci.2014 Aug 20; 34
AB  - Neuron-glial related cell adhesion molecule (NrCAM) is a regulator of axon growth and repellent guidance, and has been implicated in autism spectrum disorders. Here a novel postsynaptic role for NrCAM in Semaphorin3F (Sema3F)-induced dendritic spine remodeling was identified in pyramidal neurons of the primary visual cortex (V1). NrCAM localized to dendritic spines of star pyramidal cells in postnatal V1, where it was coexpressed with Sema3F. NrCAM deletion in mice resulted in elevated spine densities on apical dendrites of star pyramidal cells at both postnatal and adult stages, and electron microscopy revealed increased numbers of asymmetric synapses in layer 4 of V1. Whole-cell recordings in cortical slices from NrCAM-null mice revealed increased frequency of mEPSCs in star pyramidal neurons. Recombinant Sema3F-Fc protein induced spine retraction on apical dendrites of wild-type, but not NrCAM-null cortical neurons in culture, while re-expression of NrCAM rescued the spine retraction response. NrCAM formed a complex in brain with Sema3F receptor subunits Neuropilin-2 (Npn-2) and PlexinA3 (PlexA3) through an Npn-2-binding sequence (TARNER) in the extracellular Ig1 domain. A trans heterozygous genetic interaction test demonstrated that Sema3F and NrCAM pathways interacted in vivo to regulate spine density in star pyramidal neurons. These findings reveal NrCAM as a novel postnatal regulator of dendritic spine density in cortical pyramidal neurons, and an integral component of the Sema3F receptor complex. The results implicate NrCAM as a contributor to excitatory/inhibitory balance in neocortical circuits.