Otoconin-90 deletion leads to imbalance but normal hearing: A comparison with other otoconia mutants

• Published in: Neuroscience Vol. 153; no. 1; pp. 289 - 299
• Main Authors: Zhao, X, Jones, S.M, Yamoah, E.N, Lundberg, Y. Wang
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 22.04.2008; Elsevier
• Subjects: adaptation; Adaptation, Physiological - genetics; Adaptation, Physiological - physiology; Animals; balance; Biological and medical sciences; compensation; Ear and associated structures. Auditory pathways and centers. Hearing. Vocal organ. Phonation. Sound production. Echolocation; Evoked Potentials - physiology; Extracellular Matrix Proteins - genetics; Fundamental and applied biological sciences. Psychology; hearing; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Mutant Strains; Neurology; otoconia; Otolithic Membrane - abnormalities; Otolithic Membrane - physiopathology; Otolithic Membrane - ultrastructure; Postural Balance - physiology; Vertebrates: nervous system and sense organs; Vestibular Diseases - genetics; Vestibular Diseases - pathology; Vestibular Diseases - physiopathology; vestibule; Vestibule, Labyrinth - abnormalities; Vestibule, Labyrinth - physiopathology; Vestibule, Labyrinth - ultrastructure; multivariate analysis of variance; Otop1; LFA; adaptation; phosphate-buffered saline; peripheral nervous system; otopetrin 1; vestibule; ethylene diamine tetra acetate; left–right alternation; otoconin-90; balance; PNS; FFT; hearing; VsEPs; ABRs; MANOVA; OL; wt; NADPH oxidase 3; vestibular evoked potentials; PBS; scanning electron microscopy; EDTA; fast Fourier transform; Oc90; overlap; otoconia; distortion product otoacoustic emissions; DPOAEs; Nox3; compensation; SEM; wild type; auditory brainstem responses; dB peSPL; decibel peak equivalent sound pressure level; Otoconia; Hearing; Mutation; Adaptation
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2008.01.055

Abstract Our sense of gravitation and linear acceleration is mediated by stimulation of vestibular hair cells through displacement of otoconia in the utricle and saccule (the gravity receptor organ). We recently showed that otoconin-90 (Oc90) deletion led to formation of giant otoconia. In the present study, we determined the extent to which the giant otoconia affected balance and gravity receptor sensory input and compared the findings with other otoconia mutants. We employed a wide spectrum of balance behavioral tests, including reaching and air-righting reflexes, gait, swimming, beam-crossing, rotorod latencies, and a direct measure of gravity receptor input, vestibular evoked potentials (VsEPs). All tests on homozygous adult mutants consistently ranked the order of imbalance as (from worst to best) Nox3het <otopetrin 1tlt <Oc90 null<Oc90 wild type and C57Bl/6 mice using systematic statistical comparisons of the frequency of occurrence or the severity of abnormal functions. This order coincides with the degree of otoconia deficiencies and is consistent with VsEP measures. Notably, all mice (except Nox3het ) showed remarkable learned adaptation to peripheral vestibular deficits by staying on the rotating rod significantly longer in each successive trial, and the rate and extent of such learned improvements ranked the same order as their initial balance ability. Despite the vestibular morbidity, Oc90 null mice had normal hearing, as measured by auditory brainstem responses (ABRs) and distortion products of otoacoustic emissions (DPOAEs). The study demonstrates that the remnant otoconia mass in Oc90 nulls does stimulate the gravity receptor organs, which was likely responsible for the improved balance performance relative to strains with absent otoconia. Furthermore, the combination of direct electrophysiological measures and a series of behavioral tests can be used to interpret the imbalance severity arising from altered inputs from the gravity receptor end organ.