Morphology, GluR1 and GRIP-C localization differ in octopus cells of C57BL6 and B6Cast mice

Abstract

The C57BL6 mouse (B6) is homozygous for the gene for age-related hearing loss (ahl/ahl) and shows normal adult-like hearing before subtle changes in hearing begin at about 30 days of age. The B6Cast mouse is congenic to B6, having the wild type allele for normal hearing from Castaneous Ei on a B6 background. It has normal hearing throughout most of its lifespan. This study characterized the morphology of octopus cell (OC) somata in the posterior-ventral cochlear nucleus and of synaptic terminals on the OC somata in 8-week-old B6 and B6Cast mice, and the immunolocalization of antibodies to GluR1 (glutamate receptor subunit 1) and GRIP-C (glutamate receptor interacting protein-C terminus). By 8 weeks of age there are significant changes in the morphology of OCs and synaptic terminals around their somata in B6 mice compared to B6Cast mice. The distribution of immunoreactivity for the proteins GluR1 and GRIP is also significantly different in B6 mice from that in B6Cast mice. The modest degenerative changes reported in some B6 outer hair cells of the basal turn at this age do not seem adequate to explain the major changes observed in most OCs at a time when physiological studies show that many measures of the animals’ hearing are still near normal. The findings suggest that changes in the α-amino-3-hydroxy-5-methyl-4-isoxazole glutamate receptor subunits and/or their binding proteins are part of the phenotype of ahl, and may reflect a role of the glutamate receptor pathway in the mechanism of ahl.