A novel mode of off-frequency hearing as a result of defective outer hair cells hair bundles unveiled by Nherf1-/- mice

Abstract

Nherf1, a PDZ-domain-containing protein, was identified in the hair bundle in differentiating outer hair cells (OHCs). Nherf1-/- mice showed apparently mild hearing-threshold elevations at mid/high sound frequencies, associated to OHC hair-bundle shape anomalies, prominent in the basal cochlea. This mild impact on hearing sensitivity was discordant with the finding of almost non-responding OHCs in the basal cochlea as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Unlike normal mice, responses of Nherf1-/- mice to high-frequency test tones were not masked by tones of neighboring frequencies. Efficient masker tones displayed unusual characteristics: maximal efficiency at lower frequencies (up to two octaves lower than the test tone), and at low levels (up to 25 dB below test-tone level). This, and the relative growth of the masker and test tones, suggests that mid-high frequency tones of moderate intensity are detected off-frequency, in the functionally unaffected apical cochlear region. Our results establish that Nherf1 is critical for hair bundle morphogenesis and reveal a novel mode of off-frequency detection, probably involving the persistent contact between OHCs and the tectorial membrane. These findings suggest how to circumvent major pitfalls in hearing assessment of some patients, by avoiding misleading interpretations of hearing thresholds.