Direct Intracellular Signaling by the Carboxy terminus of NMDA Receptor GluN2 Subunits Regulates Dendritic Morphology in Hippocampal CA1 Pyramidal Neurons. (1st January 2019)

• Record Type: Journal Article
• Authors: Keith, Rachel E.; Azcarate, Jessica M.; Keith, Matthew J.; Hung, Carey W.; Badakhsh, Maryam F.; Dumas, Theodore C.
• Is Part Of: Neuroscience. Volume 396(2019)
• Page Start: 138
• Page End: 153
• Publication Date: 2019-01-01
• Subjects: CaMKII calmodulin-dependent protein kinase II -- CTD carboxy-terminal domain -- eGFP enhanced green fluorescent protein -- NMDARs N-methyl-d-aspartate receptors -- NTD amino-terminal domain -- PBS phosphate-buffered saline -- TMDs transmembrane domains; NMDA -- dendritic morphology -- protein signaling -- GluN2 -- transgenic -- development; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.11.021
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: eGFP expression reveals a greater dendritic arbor extent than Golgi-Cox staining. Gender differences in morphology were found solely in Golgi-Cox-stained neurons. ABc mice have a longer total arbor path, average apical length and total basal length. BAc mice and wildtype mice did not differ in neuron morphology. NMDAR-dependent intracellular signaling regulates dendritic morphology. Abstract: N-methyl-d -aspartate receptors (NMDARs) are glutamatergic receptors that take part in excitatory synaptic transmission and drive functional and structural neuronal plasticity, including activity-dependent changes in dendritic morphology. Forebrain NMDARs contribute to neuronal plasticity in at least two ways: through calcium-mediated processes or via direct intracellular postsynaptic signaling. Both properties are regulated by the GluN2 subunits. However, the separate contributions of these properties to the regulation of dendritic morphology are unknown. We created transgenic mice that express chimeric GluN2 subunits and examined the impact on pyramidal cell dendritic morphology in hippocampal region CA1. Golgi-Cox impregnation and transgenic expression of green fluorescent protein were employed to visualize dendritic arbors. In adult mice with a predominantly native GluN2A background, overexpression of the GluN2B carboxy terminus increased the total path of the dendritic arbor without affecting branch number or tortuosity. Overexpressing the amino terminus and transmembrane domains of GluN2B had little effect. It may be inferred from these results that NMDAR-dependent intracellular signaling regulates dendritic morphology of hippocampal pyramidal cells more so than calcium conductance dynamics. The findings add to the understanding of NMDAR-mediated signaling in hippocampal neurons and support re-investigation of the molecular underpinnings of NMDAR involvement in postnatal dendrite maturation.