Developmental regulation of GABAergic interneuron branching and synaptic development in the prefrontal cortex by soluble neural cell adhesion molecule

Mol Cell Neurosci. 2008 Apr;37(4):781-93. doi: 10.1016/j.mcn.2008.01.006. Epub 2008 Jan 17.


Neural cell adhesion molecule, NCAM, is an important regulator of neuronal process outgrowth and synaptic plasticity. Transgenic mice that overexpress the soluble NCAM extracellular domain (NCAM-EC) have reduced GABAergic inhibitory and excitatory synapses, and altered behavioral phenotypes. Here, we examined the role of dysregulated NCAM shedding, modeled by overexpression of NCAM-EC, on development of GABAergic basket interneurons in the prefrontal cortex. NCAM-EC overexpression disrupted arborization of basket cells during the major period of axon/dendrite growth, resulting in decreased numbers of GAD65- and synaptophysin-positive perisomatic synapses. NCAM-EC transgenic protein interfered with interneuron branching during early postnatal stages when endogenous polysialylated (PSA) NCAM was converted to non-PSA isoforms. In cortical neuron cultures, soluble NCAM-EC acted as a dominant inhibitor of NCAM-dependent neurite branching and outgrowth. These findings suggested that excess soluble NCAM-EC reduces perisomatic innervation of cortical neurons by perturbing axonal/dendritic branching during cortical development.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cells, Cultured
  • Humans
  • Interneurons / cytology
  • Interneurons / physiology*
  • Mice
  • Mice, Transgenic
  • Neural Cell Adhesion Molecules / biosynthesis
  • Neural Cell Adhesion Molecules / genetics
  • Neural Cell Adhesion Molecules / physiology*
  • Prefrontal Cortex / cytology
  • Prefrontal Cortex / embryology*
  • Prefrontal Cortex / physiology*
  • Protein Structure, Tertiary / genetics
  • Synapses / genetics
  • Synapses / physiology*
  • gamma-Aminobutyric Acid / physiology*


  • Neural Cell Adhesion Molecules
  • gamma-Aminobutyric Acid