Inner hair cell responses to the 2f1-f2 intermodulation distortion product

Recordings of dc and ac receptor potentials from pigmented guinea pig inner hair cells indicate strong responses to the 2f1-f2 intermodulation tone when f1 and f2 are greater than the hair cell characteristic frequency and do not cause a response when given individually. The effective magnitude of this cubic distortion product (CDP) was about 25-30 dB below equal sound level primaries over a 20-30-dB range of their sound levels. The relative strength of the CDP declined at a rate greater than 180-dB/oct separation of the primaries. When magnitude of f1 or f2 was held constant, the growth of CDP was nonmonotonic, exhibiting a distinct maximum. With a constant level of f1 or f2, optimal CDP was produced when the level of f2 was 10-15 dB greater than f1. Strong two-tone suppression from the primaries has a role in shaping the CDP growth. The ac receptor potentials of the CDP show a 150 degrees-200 degrees phase shift when the primaries are increased over a 50-dB range. These results support the hypothesis of a propagated CDP in the cochlea and are consistent with the major features of related studies of human psychoacoustic experiments, afferent nerve neural rate functions, and ear canal distortion products.     

Influence of direct current on dc receptor potentials from cochlear inner hair cells in the guinea pig

Inner hair cell responses to sound were monitored while direct current was applied across the membranous labyrinth in the first turn of the guinea pig cochlea. The current injection electrodes were positioned in the scala vestibuli and on the round window membrane. Positive and negative current (less than 100 microA) caused changes in the sound-evoked dc receptor potentials which were dependent on the sound frequency and intensity. The frequencies most affected by this extracellular current were those comprising the "tip" portion of the inner hair cell frequency tuning characteristic (FTC). The influence of current increased with increasing frequency. Positive current increased the amount of dc receptor potential for the affected frequencies while negative current decreased the potential. Current-induced changes (on a percentage basis) were greater for low intensity sounds and the negative current direction. These frequency specific changes are evidenced as a loss in sensitivity for the tip area of the FTC and a downward shift of the inner hair cell characteristic frequency. Larger current levels (greater than 160 microA) cause more complex changes including unrecoverable loss of cell performance. In separate experiments positive and negative currents (less than 1.1 microA) were injected into the inner hair cell from the recording electrode during simultaneous measurement of the sound-evoked dc receptor potential. This condition caused a shift in IHC sensitivity that was independent of sound frequency and intensity. Positive current decreased the sensitivity of the level of the cell while negative current increased the responses. The effect of current level on sound-evoked dc receptor potential was nonlinear, as comparatively greater increases in cell response were observed for negative than decreases for positive current. The intracellular current injection results are accounted for by the mechano-resistive model of hair cell transduction, where nonlinear responses with current level may reflect outward rectification. Response changes induced by extracellular current are evidence of current effects on both inner and outer hair cells. The frequency and intensity dependences are hypothesized to represent voltage mediated control of inner hair cell response by the outer hair cells.     

Effects of electrical polarization on inner hair cell receptor potentials

Ac and dc receptor potential components in response to tone-burst stimuli were measured from inner hair cells in the third cochlear turn of the guinea pig. Comparisons were sought between conditions when constant polarizing current was injected into the cell through the recording electrode and when there was no extrinsic current. Hyperpolarization of the cell increased all responses, while depolarization decreased them. The input-output functions were vertically translated by current injection. The extent of translation was a function of current level. In addition, the amount of current-induced change was frequency dependent. Largest changes were seen at low frequencies and the current-induced change tended toward a constant high-frequency asymptote between 1-2 kHz. Changes in the dc response component were considerably in excess of those for the fundamental ac response. The frequency-dependent effects are quantified with the aid of a hair cell circuit model [P. Dallos, Hear. Res. 14, 281-291 (1984)]. It is assumed that the quantity altered by polarizing current (actually by the transmembrane voltage) is the resistance of the cell's basolateral membrane.     

Inner hair cell response patterns: implications for low-frequency hearing.

Inner hair cell (IHC) responses to tone-burst stimuli were measured from three locations in the apical half of the guinea pig cochlea. In addition to the measurement of ac receptor potentials, average intracellular voltages, reflecting both ac and dc components of the receptor potential, were computed and compared to determine how bandwidth changes with level. Companion phase measures were also obtained and evaluated. Data collected from turn 2, where best frequency (BF) is approximately 4000 Hz, indicate that frequency response functions are asymmetrical with steeper slopes above the best frequency of the cell. However, in turn 4, where BF is around 250 Hz, the opposite behavior is observed and the steepest slopes are measured below BF. The data imply that cochlear filters are generally asymmetrical with steeper slopes above BF. High-pass filtering by the middle ear serves to reduce this asymmetry in turn 3 and to reverse it in turn 4. Apical response patterns are used to assess the degree to which the middle ear transfer function, the IHC's velocity dependence and the shunting effect of the helicotrema influence low-frequency hearing in guinea pigs. Implications for low-frequency hearing in man are also discussed.     

Comment on "Mutual suppression in the 6 kHz region of sensitive chinchilla cochleae" [J. Acoust. Soc. Am. 121, 2805-2818 (2007)

Rhode [J. Acoust. Soc. Am. 121, 2805-2818 (2007)] acknowledges that two-tone neural rate responses for low-side suppression differ from those measured in basilar membrane mechanics, making one question whether this aspect of suppression has a mechanical correlate. It is suggested here that signal coding between mechanical and neural processing stages may be responsible for the fact that the total rate response (but not the basilar membrane response) for low-frequency suppressors is smaller than that for the probe-alone condition. For example, the velocity dependence of inner hair cell (IHC) transduction, membrane/synaptic filtering and the sensitivity difference between ac and dc components of the IHC receptor potential all serve to reduce excitability for low-side suppressors at the single-unit level. Hence, basilar membrane mechanics may well be the source of low-side suppression measured in the auditory nerve.     

Flow of endolymph in the inner spiral sulcus and the subtectorial space

Flows of endolymph within the inner spiral sulcus and the subtectorial space are studied analytically. These flows are driven by boundary displacements and scala media pressure, all prescribed in the form of traveling sine waves with uniform amplitude, wave speed, and wavelength. Prescribed boundary displacements have no axial components and are assumed "small." In the subtectorial space, waves are further assumed "long," and inner and outer hair cells' stereocilia are represented by permeable barriers. Boundary motions of the subtectorial space are assumed to be associated with basilar membrane motion. The localized boundary motions that would presumably accompany independent outer hair cell motions are not admitted. The pressure drop across the barrier representing the inner hair cells' stereocilia is evaluated for four specific input conditions. The results are used to assess its relative sensitivity to three types of boundary displacement and to examine the contribution of endolymph flow to the "second filter." The model predicts the introduction of appreciable tuning (102.3 dB/octave) into the auditory signal between the stages of relative normal displacement of the boundaries of the subtectorial space and the generation of a pressure drop across the inner hair cells' stereocilia. The outer barrier is removed from the model, and the pressure drop across the inner barrier is reevaluated for the same four cases to study its sensitivity to destruction of the outer hair cells' stereocilia. These results are examined in light of data by Robertson and Johnstone [D. Robertson and B. M. Johnstone, J. Acoust. Soc. Am. 66, 466-469 (1979)].     

The dynamic range of inner hair cell and organ of Corti responses

Inner hair cell (IHC) and organ of Corti (OC) responses are measured from the apical three turns of the guinea pig cochlea, allowing access to regions with best, or most sensitive, frequencies at approximately 250, 1000, and 4000 Hz. In addition to measuring both ac and dc receptor potentials, the average value of the half-wave rectified response (AVEHR) is computed to better reflect the signal that induces transmitter release. This measure facilitates comparisons with single-unit responses in the auditory nerve. Although IHC ac responses exhibit compressive growth, response magnitudes at high levels depend on stimulus frequency. For example, IHCs with moderate and high best frequencies (BF) exhibit more linear responses below the BF of the cell, where higher sound-pressure levels are required to approach saturation. Because a similar frequency dependence is observed in extracellular OC responses, this phenomenon may originate in cochlear mechanics. At the most apical recording location, however, the pattern documented at the base of the cochlea is not seen in IHCs with low BFs around 250 Hz. In fact, more linear behavior is measured above the BF of the cell. These frequency-dependent features require modification of cochlear models that do not provide for longitudinal variations and generally depend on a single stage of saturation located at the synapse. Finally, behavior of dc and AVEHR responses suggests that a single IHC is capable of coding intensity over a large dynamic range [Patuzzi and Sellick, J. Acoust. Soc. Am. 74, 1734-1741 (1983); Smith et al., in Hearing--Physiological Bases and Psychophysics (Springer, Berlin, 1983); Smith, in Auditory Function (Wiley, New York, 1988)] and that information compiled over wide areas along the cochlear partition is not essential for loudness perception, consistent with psychophysical results [Viemeister, Hearing Res. 34, 267-274 (1988)].     

A biophysical model of an inner hair cell

Whole-cell patch-clamp recordings on isolated inner hair cells (IHCs) of guinea pig cochleae have revealed the presence of voltage-gated potassium channels. A biophysical model of an IHC is presented that indicates activation of slow voltage-gated potassium channels may lead to receptor potentials whose dc component decreases during the stimulus, and membrane potential hyperpolarizes when the stimulus is turned off. Both the decreasing dc and the hyperpolarization are, respectively, consistent with rapid adaptation and suppression of spontaneous rate in the auditory nerve. Receptor potentials recorded in vivo do not show these features, and when a nonspecific leak is included in the model to simulate microelectrode impalement, the model's receptor potentials become similar to those in vivo. The nonspecific leak creates an electrical shunt that masks slow channel activity and allows the cell to depolarize. Both the decreasing dc and the hyperpolarization are sensitive to the resting potential. Because the reported resting potentials in vivo and in vitro differ greatly, the model is used to investigate homeostatic mechanisms responsible for the resting potential. It is found that the voltage-gated potassium channels have the greatest influence on the resting potential, but that the standing transducer current may be sufficient to eliminate the decreasing dc and after-stimulus hyperpolarization.     

An auditory-periphery model of the effects of acoustic trauma on auditory nerve responses

Acoustic trauma degrades the auditory nerve's tonotopic representation of acoustic stimuli. Recent physiological studies have quantified the degradation in responses to the vowel /E/ and have investigated amplification schemes designed to restore a more correct tonotopic representation than is achieved with conventional hearing aids. However, it is difficult from the data to quantify how much different aspects of the cochlear pathology contribute to the impaired responses. Furthermore, extensive experimental testing of potential hearing aids is infeasible. Here, both of these concerns are addressed by developing models of the normal and impaired auditory peripheries that are tested against a wide range of physiological data. The effects of both outer and inner hair cell status on model predictions of the vowel data were investigated. The modeling results indicate that impairment of both outer and inner hair cells contribute to degradation in the tonotopic representation of the formant frequencies in the auditory nerve. Additionally, the model is able to predict the effects of frequency-shaping amplification on auditory nerve responses, indicating the model's potential suitability for more rapid development and testing of hearing aid schemes.     

Cochlear microphonics and the initiation of spikes in the auditory nerve: correlation of single-unit data with neural and receptor potentials recorded from the round window

On the basis of comparisons of responses of guinea pig ganglion cells and inner hair cells to intense low-frequency tones, Sellick et al. [Hear. Res. 7, 199-221 (1982)] have proposed that basal inner hair cells can be depolarized (and thus, VIII-N. spikes generated) by the extracellular microphonic generated during hyperpolarization of outer hair cells. VIII-N. data for the chinchilla have been presented that, to a first approximation, support such a hypothesis [Ruggero and Rich, J. Acoust. Soc. Am. 73, 2096-2108 (1983)]. However, an apparent discrepancy exists in our results, vis à vis Sellick et al.'s hypothesis, in that basal fiber near-threshold responses precede maximal negativity of the round window microphonic (i.e., maximal hyperpolarization of outer hair cells) by up to 90 degrees (but generally less than 45 degrees), depending on frequency. It is shown here that the discrepancy is resolved if certain nonlinear phase changes and overall distortion of the microphonic waveshapes, both of which occur at intense stimulus levels, are taken into account. It is also shown that compound action potentials (AP's), superimposed on the round window microphonics, can be identified at multiple times within each stimulus cycle, closely matching the near-threshold response phases of single-unit excitation. AP1 is nearly synchronous with the negative-to-positive transition of round window microphonics and with the excitation of fibers innervating apical-to-middle cochlear regions. AP2 is synchronous with the positive-to-negative transition of the microphonics and with the excitation of basal fibers. One or two other AP's probably reflect "peak splitting" in the responses of both basal and apical fibers.     

A hardware cochlear nonlinear preprocessing model with active feedback

A hardware model of the nonlinear preprocessing established in the inner ear consisting of 90 sections corresponding to a frequency range from 900 to 8000 Hz is described. The model is based on assumptions described by Zwicker [Biol. Cybern. 35, 243-250 (1979)]: The outer hair cells act as saturating nonlinear mechanical amplifiers which feed back to the vibration of the basilar membrane while only the inner hair cells transfer information towards higher centers. The model shows many effects which correlate very closely to physiological and psychoacoustical counterparts. Quantitative data on the level-dependence of frequency responses and phase responses as well as an example of suppression are outlined.     

Real time decomposition of speech into modulated components

Motivated by the active process of the outer hair cell (OHC) in the mammalian inner ear, a real time decomposition of speech into modulated components is presented. A generalized phase lock loop (GPLL) was applied to decompose the speech signal into its envelope and positive instantaneous frequency (PIF) parts, which can be further processed and represented by timing information alone. A log-derivative operator is applied to the bandpass signal. Analytic and antianalytic components occupying non overlapping frequency bands are separated by filtering. The proposed algorithms are used to represent speech signals processed through a bandpass filter bank.     

Outer hair cell piezoelectricity: frequency response enhancement and resonance behavior

Stretching or compressing an outer hair cell alters its membrane potential and, conversely, changing the electrical potential alters its length. This bi-directional energy conversion takes place in the cell's lateral wall and resembles the direct and converse piezoelectric effects both qualitatively and quantitatively. A piezoelectric model of the lateral wall has been developed that is based on the electrical and material parameters of the lateral wall. An equivalent circuit for the outer hair cell that includes piezoelectricity shows a greater admittance at high frequencies than one containing only membrane resistance and capacitance. The model also predicts resonance at ultrasonic frequencies that is inversely proportional to cell length. These features suggest all mammals use outer hair cell piezoelectricity to support the high-frequency receptor potentials that drive electromotility. It is also possible that members of some mammalian orders use outer hair cell piezoelectric resonance in detecting species-specific vocalizations.     

Vibration responses of the organ of Corti and the tectorial membrane to electrical stimulation

Coupling of somatic electromechanical force from the outer hair cells (OHCs) into the organ of Corti is investigated by measuring transverse vibration patterns of the organ of Cori and tectorial membrane (TM) in response to intracochlear electrical stimulation. Measurement places at the organ of Corti extend from the inner sulcus cells to Hensen's cells and at the lower (and upper) surface of the TM from the inner sulcus to the OHC region. These locations are in the neighborhood of where electromechanical force is coupled into (1) the mechanoelectrical transducers of the stereocilia and (2) fluids of the organ of Corti. Experiments are conducted in the first, second, and third cochlear turns of an in vitro preparation of the adult guinea pig cochlea. Vibration measurements are made at functionally relevant stimulus frequencies (0.48-68 kHz) and response amplitudes (<15 nm). The experiments provide phase relations between the different structures, which, dependent on frequency range and longitudinal cochlear position, include in-phase transverse motions of the TM, counterphasic transverse motions between the inner hair cell and OHCs, as well as traveling-wave motion of Hensen's cells in the radial direction. Mechanics of sound processing in the cochlea are discussed based on these phase relationships.     

Inner hair cell responses to tonal stimulation in the presence of broadband noise

The effects of broadband noise (BBN) on the tone-evoked de receptor potential from inner hair cells of guinea pigs were measured. The effects of the noise were: suppression of the receptor potential, no net change, or greater depolarization relative to the tone alone, evoked receptor potential. The effects appear to be consistent with a two-tone suppression hypothesis. The time course of the suppression effect is immediate and constant in time. This observation suggests no obvious involvement of a local feedback loop in outer hair cells or one depending on the efferent nerves. Inner hair cell "sensitivity" is a variable in the magnitude of the suppression. Comparison of masked, tone-evoked de receptor potential intensity functions to responses from auditory-nerve fibers (taken from the literature for experiments using a similar paradigm) differentiates the phenomena of suppression and adaptation in the auditory periphery.     

A comparison between basilar membrane and inner hair cell receptor potential input-output functions in the guinea pig cochlea

Intracellular recordings were made from inner hair cells and basilar membrane motion was measured at a similar place, but in different preparations, in the first turn of the guinea pig cochlea. Potential recordings were made using glass microelectrodes and mechanical measurements were made using the M?ssbauer technique. Intensity functions of DC receptor potential and basilar membrane velocity in animals with good and poor thresholds are presented. In animals with good thresholds, stimuli at and above the characteristic frequency produce similarly compressive input-output functions for both inner hair cell receptor potentials and basilar membrane motion. However, for frequencies lower than the characteristic frequency, receptor potential input-output functions obtained from animals in good and poor condition show saturation at high stimulus intensities at which basilar membrane motion is linear. This discrepancy is believed to be due to a nonlinear inner hair cell transduction mechanism. We propose that nonlinearity observed in receptor potential input-output functions is a consequence of the simple cascading of a frequency-dependent nonlinear mechanical input and a frequency-independent nonlinear transduction process.     

On the mechanoelectrical coupling in the cochlear outer hair cell

Outer hair cell electromotility, a manifestation of the interconnection between the mechanical and electrical processes occurring in outer hair cells, is believed to be an important contribution to the active cochlea. Two modes of mechanoelectrical coupling in the outer hair cell wall are studied: the potential shift caused by mechanical loading under the wall charge preservation conditions and the current (transferred charge) caused by mechanical loading under the voltage-clamp conditions. By using the previously reported elastic moduli of the wall and components of the active force, the potential shift under the charge preservation conditions is derived. This shift is expressed in terms of the wall strains and the active force derivatives with respect to the wall potential. The magnitudes of the potential shift corresponding to the conditions of cell inflation, axial stretch (compression), and the micropipet aspiration are estimated. In the last case, the distribution of the potential shift along the cell wall is also demonstrated. The potential shift can reach -20(-)-40 mV under the conditions of the micropipet aspiration or cell inflation. Such shift is much smaller under the condition of cell stretch (compression). The current and the charge transfer caused by the cell stretch under the voltage-clamp conditions is analyzed, and shows good agreement of predictions with experimental data.     

Morphometric analysis of hair cells in the chinchilla cochlea

Ten chinchilla cochleas which ranged in length from 16.00 to 19.71 m were used for this study. The cross-sectional area and perimeter of the inner and outer hair cells and their nuclei were determined at two locations per cochlear turn and at the junction between each of the turns (11 locations from apex to base). Some interanimal variation in hair cell dimensions was noted. However, none of these size variations could be attributed to any known differences among the animals. It was concluded that the data reported here represent the natural variation in hair cell size in chinchillas. The data establish a baseline to which the dimensions of cells from abnormal cochleas can be compared, regardless of the length of the cochlea or the base-to-apex location of the cells.     

Dc-bias-field-induced dielectric relaxation and ac conduction in CaCu3Ti4O12 ceramics

The dielectric relaxation and ac conduction of CaCu₃Ti₄O₁₂ (CCTO) ceramics were investigated at different temperatures under a dc bias. The dc bias gives rise to space charge accumulation, i.e. an electrode response, resulting in the significant increase of dielectric permittivity and dielectric loss tangent. Two Debye-like relaxations, arising from electrode and grain boundary responses, are present at low frequency with an increase of the dc bias. The electrode and grain boundary relaxations are distinguished according to the impedance spectroscopy and the frequency-dependent ac conductivity. The relaxation times of electrode and grain boundary relaxation are 0.955 ms and 0.026 ms, respectively, with a dc bias of 10 V at 328 K.