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.     

Outer hair cell active force generation in the cochlear environment

Outer hair cells are critical to the amplification and frequency selectivity of the mammalian ear acting via a fine mechanism called the cochlear amplifier, which is especially effective in the high-frequency region of the cochlea. How this mechanism works under physiological conditions and how these cells overcome the viscous (mechanical) and electrical (membrane) filtering has yet to be fully understood. Outer hair cells are electromotile, and they are strategically located in the cochlea to generate an active force amplifying basilar membrane vibration. To investigate the mechanism of this cell's active force production under physiological conditions, a model that takes into account the mechanical, electrical, and mechanoelectrical properties of the cell wall (membrane) and cochlear environment is proposed. It is shown that, despite the mechanical and electrical filtering, the cell is capable of generating a frequency-tuned force with a maximal value of about 40 pN. It is also found that the force per unit basilar membrane displacement stays essentially the same (40 pNnm) for the entire linear range of the basilar membrane responses, including sound pressure levels close to hearing threshold. Our findings can provide a better understanding of the outer hair cell's role in the cochlear amplifier.     

A Brownian energy depot model of the basilar membrane oscillation with a braking mechanism

High auditory sensitivity, sharp frequency selectivity, and spontaneous otoacoustic emissions are signatures of active amplification of the cochlea. The human ear can also detect very large amplitude sounds without being damaged, as long as the exposed time is not too long. The outer hair cells are believed to be the best candidate for the active force generator of the mammalian cochlea. In this paper, we propose a new model for the basilar membrane oscillation which describes both an active and a protective mechanism by employing an energy depot concept and a critical velocity of the basilar membrane. The compressive response of the basilar membrane at the characteristic frequency and the dynamic response to the stimulation are consistent with the experimental results. Although our model displays a Hopf bifurcation, our braking mechanism results in a hyper-compressive response to intense stimuli which is not generically observed near a Hopf bifurcation. Asymmetry seen in experimental recordings between the onset and the offset of the basilar membrane response to a sound burst is also observed in this model.     

The possible role of the cochlear frequency-position map in auditory signal coding

The frequency-position map in the cochlea is considered as part of a signal decomposition mechanism whose purpose is redundancy reduction and information compression of auditory stimuli. A logarithmic-type frequency distribution is analytically derived from a heuristic model of the autocorrelation function of auditory signals and confronted with empirical data from the cat cochlea. It is argued that the logarithmic organization of frequency along the cochlea is designed to extract the maximum amount of information with the minimum number of hair cells.     

Frequency map of the spiral ganglion in the cat

A frequency map of the cat spiral ganglion has been determined on the basis of reconstructed cochleas in which individual spiral ganglion cells were labeled with horseradish peroxidase following determination of their characteristic frequency; the cochleas were the same as those used by Liberman and Oliver [J. Comp. Neurol. 223, 163-176 (1984)]. By matching this map to one previously described for the organ of Corti [M. C. Liberman, J. Acoust. Soc. Am. 72, 1441-1449 (1982)], an estimate of the afferent innervation density of the inner hair cells was derived. Counts of myelinated nerve fibers at the habenula perforata and inner hair cells were also performed and yielded similar results in all but the most basal 10%-15% of the cochlea. Between 0.1 and 20 kHz there is a gradual monotonic increase as a function of frequency in the number of spiral ganglion cells terminating on each inner hair cell, from about eight ganglion cells per inner hair cell to about 30 ganglion cells per inner hair cell. Above 20 kHz, it seems there is a decrease to about ten ganglion cells per inner hair cell. The greatest innervation density is at approximately the region of the basilar membrane with the greatest density of inner hair cells per millimeter.     

New Evidence of Active Tuning in Cochlea

The wonderful performance of hearing systems is mainly attributed to the tuning tiltering of basilar membrane （BM）. Although theory of the cochlear mechanism has been greatly developed since the 1970s and the amplification or sensitivity of the cochlea has been concluded due to the out hair cells, the mechanics underlying the sharp-tuning or frequency selectivity of cochlea remains a puzzle. We use the cochlear translation function derived from the data of an experiment of the BM in vivo to calculate basilar responses to tone bursts, and find that there are resonant peaks with the characteristic frequency at the corresponding place in the initial and terminal part of the responses. However, when the translation function is shallower, there will be no resonant peaks in the responses. The result indicates that the sharp tuning is due to existence of the active resonant tuning mechanism.     

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.     

Effect of current stimulus on in vivo cochlear mechanics

In this paper, the influence of direct current stimulation on the acoustic impulse response of the basilar membrane (BM) is studied. A positive current applied in the scala vestibuli relative to a ground electrode in the scala tympani is found to enhance gain and increase the best frequency at a given location on the BM. An opposite effect is found for a negative current. Also, the amplitude of low-frequency cochlear microphonic at high sound levels is found to change with the concurrent application of direct current stimulus. BM vibrations in response to pure tone acoustic excitation are found to possess harmonics whose levels relative to the fundamental increase with the application of positive current and decrease with the application of negative current. A model for outer hair cell activity that couples changes in length and stiffness to transmembrane potential is used to interpret the results of these experiments and others in the literature. The importance of the in vivo mechanical and electrical loading is emphasized. Simulation results show the somewhat paradoxical finding that for outer hair cells under tension, hyperpolarization causes shortening of the cell length due to the dominance of voltage dependent stiffness changes.     

Stimulus-frequency otoacoustic emission: measurements in humans and simulations with an active cochlear model

An efficient method for measuring stimulus-frequency otoacoustic emissions (SFOAEs) was developed incorporating (1) stimulus with swept frequency or level and (2) the digital heterodyne analysis. SFOAEs were measured for 550-1450 Hz and stimulus levels of 32-62 dB sound pressure level in eight normal human adults. The mean level, number of peaks, frequency spacing between peaks, phase change, and energy-weighted group delays of SFOAEs were determined. Salient features of the human SFOAEs were stimulated with an active cochlear model containing spatially low-pass filtered irregularity in the impedance. An objective fitting procedure yielded an optimal set of model parameters where, with decreasing stimulus level, the amount of cochlear amplification and the base amplitude of the irregularity increased while the spatial low-pass cutoff and the slope of the spatial low-pass filter decreased. The characteristics of the human cochlea were inferred with the model. In the model, an SFOAE consisted of a long-delay component originating from irregularity in a traveling-wave peak region and a short-delay component originating from irregularity in regions remote from the peak. The results of this study should be useful both for understanding cochlear function and for developing a clinical method of assessing cochlear status.     

Electromotile hearing: acoustic tones mask psychophysical response to high-frequency electrical stimulation of intact guinea pig cochleae

When sinusoidal electric stimulation is applied to the intact cochlea, a frequency-specific acoustic emission can be recorded in the ear canal. Acoustic emissions are produced by basilar membrane motion, and have been used to suggest a corresponding acoustic sensation termed "electromotile hearing." Electromotile hearing has been specifically attributed to electric stimulation of outer hair cells in the intact organ of Corti. To determine the nature of the auditory perception produced by electric stimulation of a cochlea with intact outer hair cells, guinea pigs were tested in a psychophysical task. First, subjects were trained to report detection of sinusoidal acoustic stimuli and dynamic range was assessed using response latency. Subjects were then implanted with a ball electrode placed into scala tympani. Following the surgical implant procedure, subjects were transferred to a task in which acoustic signals were replaced by sinusoidal electric stimulation, and dynamic range was assessed again. Finally, the ability of acoustic pure-tone stimuli to mask the detection of the electric signals was assessed. Based on the masking effects, it is concluded that sinusoidal electric stimulation of the intact cochlea results in perception of a tonal (rather than a broadband or noisy) sound at a frequency of 8 kHz or above.     

Speech recognition as a function of high-pass filter cutoff frequency for people with and without low-frequency cochlear dead regions

Regions in the cochlea with no (or very few) functioning inner hair cells and/or neurons are called "dead regions" (DRs). The recognition of high-pass filtered nonsense syllables was measured as a function of filter cutoff frequency for hearing-impaired people with and without low-frequency (apical) cochlear DRs. The diagnosis of any DR was made using the TEN(HL) test, and psychophysical tuning curves were used to define the edge frequency (f(e)) more precisely. Stimuli were amplified differently for each ear, using the "Cambridge formula." For subjects with low-frequency hearing loss but without DRs, scores were high (about 78%) for low cutoff frequencies, remained approximately constant for cutoff frequencies up to 862 Hz, and then worsened with increasing cutoff frequency. For subjects with low-frequency DRs, performance was typically poor for the lowest cutoff frequency (100 Hz), improved as the cutoff frequency was increased to about 0.57f(e), and worsened with further increases. These results indicate that people with low-frequency DRs are able to make effective use of frequency components that fall in the range 0.57f(e) to f(e), but that frequency components below 0.57f(e) have deleterious effects. The results have implications for the fitting of hearing aids to people with low-frequency DRs.     

Speech recognition in noise as a function of highpass-filter cutoff frequency for people with and without low-frequency cochlear dead regions

Regions in the cochlea with very few functioning inner hair cells and/or neurons are called "dead regions" (DRs). Previously, we measured the recognition of highpass-filtered nonsense syllables as a function of filter cutoff frequency for hearing-impaired people with and without low-frequency (apical) DRs [J. Acoust. Soc. Am. 122, 542-553 (2007)]. DRs were diagnosed using the TEN(HL) test, and psychophysical tuning curves were used to define the edge frequency (fe) more precisely. Stimuli were amplified differently for each ear, using the "Cambridge formula." The present study was similar, but the speech was presented in speech-shaped noise at a signal-to-noise ratio of 3 dB. For subjects with low-frequency hearing loss but without DRs, scores were high (65-80%) for low cutoff frequencies and worsened with increasing cutoff frequency above about 430 Hz. For subjects with low-frequency DRs, performance was poor (20-40%) for the lowest cutoff frequency, improved with increasing cutoff frequency up to about 0.56fe, and then worsened. As for speech in quiet, these results indicate that people with low-frequency DRs are able to make effective use of frequency components that fall in the range 0.56fe to fe, but that frequency components below 0.56fe have deleterious effects.     

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.     

耳蜗中tip-link张力与静纤毛运动动力学研究

诠释耳蜗的主动感音放大机制一直是未解的医学难题.这种机制与耳蜗中外毛细胞顶端的静纤毛运动密切相关,静纤毛运动又受到tip-link张力与淋巴液流体力的调节.因此,研究静纤毛运动过程中tip-link张力是诠释耳蜗的主动感音放大机制的重要环节.本文把静纤毛视为变形体,基于泊肃叶流动理论并结合分布参数模型,推导了静纤毛运动的解析解.研究了盖膜剪切荷载作用下静纤毛和淋巴液相互作用的动力响应以及tip-link张力的变化规律.研究发现:当静纤毛的杨氏模量减小时,在小于峰值频率的区域,tip-link张力显著增大,f₂的峰值频率减小.以往的研究将静纤毛作为刚体,势必导致低频声音信号作用减弱.当系数c=0 (无黏性阻力)时,f₂频率选择特性存在;当μ=0(无压力)时,f₂频率选择特性消失,因此淋巴液可能是通过在静纤毛间产生压强的方式来调节毛束的频率特性的.另外,盖膜剪切荷载频率越高,静纤毛轴弯曲越明显,发束内外域的压强差也越大.     

Effect of outer hair cell piezoelectricity on high-frequency receptor potentials

The low-pass voltage response of outer hair cells predicted by conventional equivalent circuit analysis would preclude the active force production at high frequencies. We have found that the band pass characteristics can be improved by introducing the piezoelectric properties of the cell wall. In contrast to the conventional analysis, the receptor potential does not tend to zero and at any frequency is greater than a limiting value. In addition, the phase shift between the transduction current and receptor potential tends to zero. The piezoelectric properties cause an additional, strain-dependent, displacement current in the cell wall. The wall strain is estimated on the basis of a model of the cell deformation in the organ of Corti. The limiting value of the receptor potential depends on the ratio of a parameter determined by the piezoelectric coefficients and the strain to the membrane capacitance. In short cells, we have found that for the low-frequency value of about 2-3 mV and the strain level of 0.1% the receptor potential can reach 0.4 mV throughout the whole frequency range. In long cells, we have found that the effect of the piezoelectric properties is much weaker. These results are consistent with major features of the cochlear amplifier.     

Nonlinearities in cochlear receptor potentials and their origins

Using intracellular recording methods in vivo [P. Dallos, J. Neurosci. 5, 1591-1608 (1985)], various nonlinear characteristics of receptor potentials from hair cells located in the low-frequency region of the guinea pig cochlea have been examined. Patterns of saturation for ac and dc response components obtained from Fourier analysis and directly from averaged waveforms are studied. Growth patterns of lower harmonic components are investigated and the interesting nonmonotonic properties of even harmonics noted. The latter are seen in both inner and outer hair cell responses, primarily with stimuli near the cells' best frequency. Fundamental ac and the dc potentials occasionally exhibit nonmonotonic growth. These patterns are studied and their occurrence in inner and outer hair cell responses considered.     

Realistic mechanical tuning in a micromechanical cochlear model

Two assumptions were made in the formulation of a recent cochlear model [P.J. Kolston, J. Acoust. Soc. Am. 83, 1481-1487 (1988)]: (1) The basilar membrane has two radial modes of vibration, corresponding to division into its arcuate and pectinate zones; and (2) the impedance of the outer hair cells (OHCs) greatly modifies the mechanics of the arcuate zone. Both of these assumptions are strongly supported by cochlear anatomy. This paper presents a revised version of the outer hair cell, arcuate-pectinate (OHCAP) model, which is an improvement over the original model in two important ways: First, a model for the OHCs is included so that the OHC impedance is no longer prescribed functionally; and, second, the presence of the OHCs enhances the basilar membrane motion, so that the model is now consistent with observed response changes resulting from trauma. The OHCAP model utilizes the unusual spatial arrangement of the OHCs, the Deiters cells, their phalangeal processes, and the pillars of Corti. The OHCs do not add energy to the cochlear partition and hence the OHCAP model is passive. In spite of the absence of active processes, the model exhibits mechanical tuning very similar to those measured by Sellick et al. [Hear. Res. 10, 93-100 (1983)] in the guinea pig cochlea and by Robles et al. [J. Acoust. Soc. Am. 80, 1364-1374 (1986)] in the chinchilla cochlea. Therefore, it appears that mechanical response tuning and response changes resulting from trauma should not be used as justifications for the hypothesis of active processes in the real cochlea.     

The cochlear amplifier as a standing wave: "squirting" waves between rows of outer hair cells?

This paper draws attention to symmetric Lloyd-Redwood (SLR) waves-known in ultrasonics as "squirting" waves-and points out that their distinctive properties make them well-suited for carrying positive feedback between rows of outer hair cells. This could result in standing-wave resonance-in essence a narrow-band cochlear amplifier. Based on known physical properties of the cochlea, such an amplifier can be readily tuned to match the full 10-octave range of human hearing. SLR waves propagate in a thin liquid layer enclosed between two thin compliant plates or a single such plate and a rigid wall, conditions found in the subtectorial space of the cochlea, and rely on the mass of the inter-plate fluid interacting with the stiffness of the plates to provide low phase velocity and high dispersion. The first property means SLR wavelengths can be as short as the distance between rows of outer hair cells, allowing standing wave formation; the second permits wide-range tuning using only an order-of-magnitude variation in cochlear physical properties, most importantly the inter-row spacing. Viscous drag at the two surfaces potentially limits SLR wave propagation at low frequencies, but this can perhaps be overcome by invoking hydrophobic effects.     

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.