title: An unusually powerful mode of low-frequency sound interference due to defective hair bundles of the auditory outer hair cells.
abstract: 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.
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;Department of Otorhinolaryngology, Juntendo University Faculty of Medicine, Juntendo University, Tokyo 1138421, Japan;
authors.forename: Kazusaku
authors.initials: K
authors.lastname: Kamiya
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Vincent
authors.initials: V
authors.lastname: Michel
authors.affiliation: Laboratoire de Biophysique Sensorielle, Faculté de Médecine, and Biophysique Médicale, Centre Jean Perrin, Université d'Auvergne, 63000 Clermont-Ferrand, France;
authors.forename: Fabrice
authors.initials: F
authors.lastname: Giraudet
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Foucher
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Samantha
authors.initials: S
authors.lastname: Papal
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Isabelle
authors.initials: I
authors.lastname: Perfettini
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Sébastien
authors.initials: S
authors.lastname: Le Gal
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Verpy
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xia
authors.affiliation: Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, 30625 Hannover, Germany;
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
authors.affiliation: Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030; and.
authors.forename: Maria-Magdalena
authors.initials: MM
authors.lastname: Georgescu
authors.affiliation: Laboratoire de Biophysique Sensorielle, Faculté de Médecine, and Biophysique Médicale, Centre Jean Perrin, Université d'Auvergne, 63000 Clermont-Ferrand, France; aziz.el-amraoui@pasteur.fr christine.petit@pasteur.fr paul.avan@udamail.fr.
authors.forename: Paul
authors.initials: P
authors.lastname: Avan
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France; aziz.el-amraoui@pasteur.fr christine.petit@pasteur.fr paul.avan@udamail.fr.
authors.forename: Aziz
authors.initials: A
authors.lastname: El-Amraoui
authors.affiliation: Institut Pasteur, Génétique et Physiologie de l'Audition, 75015 Paris, France;Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche, UMR-S 1120 Paris, France;Sorbonne Universités, UPMC Univ Paris 06, Complexité Du Vivant, 75252 Paris Cedex 05, France;Collège de France, 75005 Paris, France aziz.el-amraoui@pasteur.fr christine.petit@pasteur.fr paul.avan@udamail.fr.
authors.forename: Christine
authors.initials: C
authors.lastname: Petit
mesh_terms: D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D018072:Hair Cells, Auditory, Outer / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D013016:Sound
chemical_list: D010750:Phosphoproteins; D017923:Sodium-Hydrogen Exchangers; C093376:sodium-hydrogen exchanger regulatory factor
keywords: Nherf2; Usher syndrome; hearing impairment; off-frequency detection; tail hypersensitivity