Multiple indices of the 'bounce' phenomenon obtained from the same human ears.

Loud low-frequency sounds can induce temporary oscillatory changes in cochlear sensitivity, which have been termed the 'bounce' phenomenon. The origin of these sensitivity changes has been attributed to slow fluctuations in cochlear homeostasis, causing changes in the operating points of the outer hair cell mechano-electrical and electro-mechanical transducers. Here, we acquired three objective and subjective measures resulting in a comprehensive dataset of the bounce phenomenon in each of 22 normal-hearing human subjects. We analysed the level and phase of cubic and quadratic distortion product otoacoustic emissions and the auditory thresholds before and after presentation of a low-frequency stimulus (30 Hz sine wave, 120 dB SPL, 90 s) as a function of time. In addition, the perceived loudness of temporary, tinnitus-like sensations occurring in all subjects after cessation of the low-frequency stimulus was tracked over time. The majority of the subjects (70 %) showed a significant, biphasic change of quadratic, but not cubic, distortion product otoacoustic emissions of about 3-4 dB. Eighty-six percent of the tested subjects showed significant alterations of hearing thresholds after low-frequency stimulation. Four different types of threshold changes were observed, namely monophasic desensitisations (the majority of cases), monophasic sensitisations, biphasic alterations with initial sensitisation and biphasic alterations with initial desensitisation. The similar duration of the three bounce phenomenon measures indicates a common origin. The current findings are consistent with the hypothesis that slow oscillations of homeostatic control mechanisms and associated operating point shifts within the cochlea are the source of the bounce phenomenon.

Frequency-dependent properties of the tectorial membrane facilitate energy transmission and amplification in the cochlea.

The remarkable sensitivity, frequency selectivity, and dynamic range of the mammalian cochlea relies on longitudinal transmission of minuscule amounts of energy as passive, pressure-driven, basilar membrane (BM) traveling waves. These waves are actively amplified at frequency-specific locations by a mechanism that involves interaction between the BM and another extracellular matrix, the tectorial membrane (TM). From mechanical measurements of isolated segments of the TM, we made the important new (to our knowledge) discovery that the stiffness of the TM is reduced when it is mechanically stimulated at physiologically relevant magnitudes and at frequencies below their frequency place in the cochlea. The reduction in stiffness functionally uncouples the TM from the organ of Corti, thereby minimizing energy losses during passive traveling-wave propagation. Stiffening and decreased viscosity of the TM at high stimulus frequencies can potentially facilitate active amplification, especially in the high-frequency, basal turn, where energy loss due to internal friction within the TM is less than in the apex. This prediction is confirmed by neural recordings from several frequency regions of the cochlea.

Analysis of the mouse mutant Cloth-ears shows a role for the voltage-gated sodium channel Scn8a in peripheral neural hearing loss.

Deafness is the most common sensory disorder in humans and the aetiology of genetic deafness is complex. Mouse mutants have been crucial in identifying genes involved in hearing. However, many deafness genes remain unidentified. Using N-ethyl N-nitrosourea (ENU) mutagenesis to generate new mouse models of deafness, we identified a novel semi-dominant mouse mutant, Cloth-ears (Clth). Cloth-ears mice show reduced acoustic startle response and mild hearing loss from approximately 30 days old. Auditory-evoked brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) analyses indicate that the peripheral neural auditory pathway is impaired in Cloth-ears mice, but that cochlear function is normal. In addition, both Clth/Clth and Clth/+ mice display paroxysmal tremor episodes with behavioural arrest. Clth/Clth mice also show a milder continuous tremor during movement and rest. Longitudinal phenotypic analysis showed that Clth/+ and Clth/Clth mice also have complex defects in behaviour, growth, neurological and motor function. Positional cloning of Cloth-ears identified a point mutation in the neuronal voltage-gated sodium channel alpha-subunit gene, Scn8a, causing an aspartic acid to valine (D981V) change six amino acids downstream of the sixth transmembrane segment of the second domain (D2S6). Complementation testing with a known Scn8a mouse mutant confirmed that this mutation is responsible for the Cloth-ears phenotype. Our findings suggest a novel role for Scn8a in peripheral neural hearing loss and paroxysmal motor dysfunction.

Origin of the bell-like dependence of the DPOAE amplitude on primary frequency ratio.

For low and medium sound pressure levels (SPLs), the amplitude of the distortion product otoacoustic emission (DPOAE) recorded from guinea pigs at the 2f1-f2 frequency is maximal when f2/f1 approximately 1.23 and decreases for lower and higher f2/f1 ratios. The high-ratio slope of the DPOAE dependence on the ratio of the primary frequencies might be anticipated since the f1 amplitude at the f2 place is expected to decrease for higher f2/f1 ratios. The low-ratio slope of the dependence at low and medium SPLs of the primaries is actually one slope of a notch. The DPOAE amplitude recovers from the notch when the f2/f1 ratio is further reduced. In two-dimensional space formed by the f2/f1 ratio, and the levels of the primaries, the notch is continuous and has a level-dependent phase transition. The notch is identical to that seen in DPOAE growth functions. Similar notches and phase transitions were observed for high-order and high-frequency DPOAEs. Theoretical analysis reveals that a single saturating nonlinearity is capable of generating similar amplitude notch and phase transition when the f2/f1 ratio is decreased because of the increase in f1 amplitude at the DPOAE generation place (f2 place). The difference between the DPOAE recorded from guinea pigs and humans is discussed in terms of different position of the operating point of the DPOAE generating nonlinearity.

Electrostatic interaction between stereocilia: I. Its role in supporting the structure of the hair bundle.

This paper provides theoretical estimates for the forces of electrostatic interaction between adjacent stereocilia in auditory and vestibular hair cells. Estimates are given for parameters within the measured physiological range using constraints appropriate for the known geometry of the hair bundle. Stereocilia are assumed to possess an extended, negatively charged surface coat, the glycocalyx. Different charge distribution profiles within the glycocalyx are analysed. It is shown that charged glycocalices on the apical surface of the hair cells can support spatial separation between adjacent stereocilia in the hair bundles through electrostatic repulsion between stereocilia. The charge density profile within the glycocalyx is a crucial parameter. In fact, attraction instead of repulsion between adjacent stereocilia will be observed if the charge of the glycocalyx is concentrated near the membrane of the stereocilia, thereby making this type of charge distribution unlikely. The forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena that have been recorded from the periphery of the auditory and vestibular systems.

Electrostatic interaction between stereocilia: II. Influence on the mechanical properties of the hair bundle.

This paper is based on our model [Dolgobrodov et al., 2000. Hear. Res., submitted for publication] in which we examine the significance of the polyanionic surface layers of stereocilia for electrostatic interaction between them. We analyse how electrostatic forces modify the mechanical properties of the sensory hair bundle. Different charge distribution profiles within the glycocalyx are considered. When modelling a typical experiment on bundle stiffness measurements, applying an external force to the tallest row of stereocilia shows that the asymptotic stiffness of the hair bundle for negative displacements is always larger than the asymptotic stiffness for positive displacements. This increase in stiffness is monotonic for even charge distribution and shows local minima when the negative charge is concentrated in a thinner layer within the cell coat. The minima can also originate from the co-operative effect of electrostatic repulsion and inter-ciliary links with non-linear mechanical properties. Existing experimental observations are compared with the predictions of the model. We conclude that the forces of electrostatic interaction between stereocilia may influence the mechanical properties of the hair bundle and, being strongly non-linear, contribute to the non-linear phenomena, which have been recorded from the auditory periphery.

Hair-cell numbers continue to increase in the utricular macula of the early posthatch chick.

It is generally assumed that hair-cell numbers do not increase in the vestibular epithelia of postembryonic birds after hatching. However, for the domestic chicken, it is not known when or if hair-cell numbers ever reach a steady state level during life. The numbers of hair cells in the utricular maculae of chickens from embryonic day (E) 7 to posthatch day (PH) 112 were therefore counted directly. Hair-cell numbers increase approximately 15 fold between E7 and PH2, from an average of 1,858/macula at E7 to 27,017 at PH2. Between PH2 and PH112 hair-cell numbers increase by a further 36%, to 36,650/macula. A mathematical description of the increase in hair-cell numbers observed with time predicts a half life of 29.88 days for a utricular hair cell and a steady-state turnover value of 850 hair cells/day by approximately PH60. The patterns of hair and supporting cells in the postembryonic utricular macula were also assessed. The ratios of supporting cells and hair cells, the average number of supporting cells around each hair cell, and the average number of hair cells each supporting cell contacts at PH2, PH16 and approximately 2.5 years of age are not significantly different. In contrast to the mitotically quiescent basilar papilla where all supporting cells contact at least one hair cell, 7.6% of supporting cells in the extrastriolar region of the postembryonic utricular macula do not make apical contact with a hair cell. These results indicate that hair-cell numbers in the utricular macula increase significantly after hatching, and support the concept that contact-mediated inhibition influences the proliferative potential of inner-ear supporting cells.

A descriptive model of the receptor potential nonlinearities generated by the hair cell mechanoelectrical transducer.

This paper describes a model for generating the hair cell receptor potential based on a second-order Boltzmann function. The model includes only the resistive elements of the hair cell membranes with batteries across them and the series resistance of the external return path of the transducer current through the tissue of the cochlea. The model provides a qualitative description of signal processing by the hair cell transducer and shows that the nonlinearity of the hair cell transducer can give rise to nonlinear phenomena, such as intermodulation distortion products and two-tone suppression with patterns similar to those which have been recorded from the peripheral auditory system. Particular outcomes of the model are the demonstration that two-tone suppression depends not on the saturation of the receptor current, but on the behaviour of the hair cell transducer function close to the operating point. The model also shows that there is non-monotonic growth and phase change for any spectral component, but not for the fundamental of the receptor potential.

The voltage dependence of the mechanoelectrical transducer modifies low frequency outer hair cell electromotility in vitro.

The fast outer hair cell (OHC) electromotility is voltage dependent and is driven by changes in the OHC transmembrane potential. Those changes include the receptor potential generated by the variable conductance of the mechanoelectrical transducer (Evans and Dallos, 1993). In the experiments described here, we show that the voltage dependence of the mechanoelectrical transducer influences the low frequency motile responses of OHCs to an external electrical field. OHCs were fully inserted into a glass suction pipette, the microchamber, so that only the cuticular plate and hair bundle were exposed to the bath solution. With this technique, a rectification of the mechanical response, equivalent to an excitatory displacement of the hair bundle, was observed when the command voltage inside the microchamber depolarized the apical membrane. The shape of the response persisted when the OHC voltage-gated conductances were blocked. Following treatment of the hair bundle with BAPTA or dihydrostreptomycin, which are known to impair transduction function (Assad et al., 1991; Kroese et al., 1989), rectification of the motile response disappeared.