title: Developmental regulation of GABAergic interneuron branching and synaptic development in the prefrontal cortex by soluble neural cell adhesion molecule.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, and Silvio Conte Center for Schizophrenia Research, University of North Carolina School of Medicine, Chapel Hill, NC 27599, USA.
authors.forename: Leann Hinkle
authors.initials: LH
authors.lastname: Brennaman
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Maness
mesh_terms: 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*
chemical_list: D019006:Neural Cell Adhesion Molecules; D005680:gamma-Aminobutyric Acid