unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 111; no. 25; pp. 9307 - 9312
• Main Authors: Kamiya, Kazusaku, Michel, Vincent, Giraudet, Fabrice, Riederer, Brigitte, Foucher, Isabelle, Papal, Samantha, Perfettini, Isabelle, Le Gal, Sébastien, Verpy, Elisabeth, Xia, Weiliang, Seidler, Ursula, Georgescu, Maria-Magdalena, Avan, Paul, El-Amraoui, Aziz, Petit, Christine
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 24.06.2014; National Acad Sciences
• Subjects: Animals; Audio frequencies; Auditory Perception - physiology; Biological Sciences; Cells; Cochlea; Ears & hearing; Hair; Hair cells; Hair Cells, Auditory, Outer - cytology; Hair Cells, Auditory, Outer - metabolism; Human health and pathology; Life Sciences; Membranes; Mice; Mice, Knockout; Outer hair cells; Phosphoproteins - genetics; Phosphoproteins - metabolism; Protease inhibitors; Proteins; Rodents; Sensory Organs; Sodium-Hydrogen Exchangers - genetics; Sodium-Hydrogen Exchangers - metabolism; Sound; Stereocilia; Theatrical masks; Vibration; Nherf2; hearing impairment; tail hypersensitivity; Usher syndrome; off-frequency detection
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1405322111

A detrimental perceptive consequence of damaged auditory sensory hair cells consists in a pronounced masking effect exerted by low-frequency sounds, thought to occur when auditory threshold elevation substantially exceeds 40 dB. Here, we identified the submembrane scaffold protein Nherf1 as a hair-bundle component of the differentiating outer hair cells (OHCs). Nherf1 ⁻/⁻ mice displayed OHC hair-bundle shape anomalies in the mid and basal cochlea, normally tuned to mid- and high-frequency tones, and mild (22–35 dB) hearing-threshold elevations restricted to midhigh sound frequencies. This mild decrease in hearing sensitivity was, however, discordant with almost nonresponding OHCs at the cochlear base as assessed by distortion-product otoacoustic emissions and cochlear microphonic potentials. Moreover, unlike wild-type mice, responses of Nherf1 ⁻/⁻ mice to high-frequency (20–40 kHz) test tones were not masked by tones of neighboring frequencies. Instead, efficient maskers were characterized by their frequencies up to two octaves below the probe-tone frequency, unusually low intensities up to 25 dB below probe-tone level, and growth-of-masker slope (2.2 dB/dB) reflecting their compressive amplification. Together, these properties do not fit the current acknowledged features of a hypersensitivity of the basal cochlea to lower frequencies, but rather suggest a previously unidentified mechanism. Low-frequency maskers, we propose, may interact within the unaffected cochlear apical region with midhigh frequency sounds propagated there via a mode possibly using the persistent contact of misshaped OHC hair bundles with the tectorial membrane. Our findings thus reveal a source of misleading interpretations of hearing thresholds and of hypervulnerability to low-frequency sound interference.