Developmental regulation of GABAergic interneuron branching and synaptic development in the prefrontal cortex by soluble neural cell adhesion molecule.
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.
Brennaman
Leann Hinkle
LH
Department of Biochemistry and Biophysics, and Silvio Conte Center for Schizophrenia Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
Maness
Patricia F
PF
D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017397:Prefrontal Cortex / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D017434:Protein Structure, Tertiary / Q000235:genetics; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D019006:Neural Cell Adhesion Molecules; D005680:gamma-Aminobutyric Acid