Basilar membrane mechanics at the base of the chinchilla cochlea. II. Responses to low-frequency tones and relationship to microphonics and spike initiation in the VIII nerve

Low-frequency stimuli (40- to 1000-Hz tones) have been used to correlate the motion of the 8-to 9-kHz place of the chinchilla basilar membrane with the cochlear microphonics recorded at the round window and with the responses of auditory nerve fibers with appropriate characteristic frequency. At the lowest stimulus frequencies, maximum displacement of the basilar membrane toward scala tympani occurs in near synchrony with maximum rarefaction at the eardrum and maximum negativity at the round window; at higher frequencies, the mechanical and microphonic response phases progressively lag rarefaction, reaching - 240 deg at 1000 Hz. At most frequencies (40-1000 Hz) near-threshold neural responses, once corrected for neural travel-time and synaptic delays, somewhat lead (by some 40 deg) maximal scala tympani displacement and maximal negativity of the round window microphonics. The variation of sensitivity with frequency is similar for basilar membrane displacement and microphonic responses: Under open-bulla conditions, sensitivity is constant for frequencies between 100 and 1000 Hz; below 100 Hz, sensitivity decreases at rates close to 12 dB/oct toward lower frequencies. Neural response sensitivity matches BM displacement more closely than BM velocity.     

Chinchilla auditory-nerve responses to low-frequency tones

Single unit activity was recorded in the auditory nerves of chinchillas. Period histograms were constructed for responses to tones with frequencies 30-1000 Hz. For low-frequency tones at near-threshold levels, peak period histogram phases for low- and medium-best-frequency (BF) neurons (less than or equal to kHz) ranged from synchronous with condensation at the eardrum to 90 degrees leading it. At near-threshold (but high absolute) levels, high-BF (greater than or equal to 8 kHz) neurons responded in phase with rarefaction. At even higher levels, period histograms for responses of high-BF neurons tended to become bimodal, with one of the modes lagging rarefaction by 90 degrees. Using cochlear microphonics as an indicator of basilar membrane (BM) displacement, at threshold levels, response phase of low- and medium-BF neurons fall within a range between displacement and velocity of the BM toward scala vestibuli. High-BF neurons respond, at threshold (but high) intensities, in phase with BM displacement toward scala tympani. The rates of growth of frequency sensitivity in responses of low-BF (+ 18 dB/oct) and high-BF (+ 12 dB/oct) neurons are consistent with preferred response phases corresponding to BM SV velocity and ST displacement, respectively. At supra-threshold levels high-BF neurons may fire preferentially to both scala tympani displacement and scala vestibuli velocity. These results support the notion that, for high-intensity, low-frequency stimuli, OHC hyperpolarization can induce excitation of the dendrites innervating IHCs.     

Characterization of an EPSP-like potential recorded remotely from the round window

The whole-nerve cochlear action potential (CAP), to tone burst stimulation, was recorded before and after application of tetrodotoxin (TTX) to the intact round window (RW) membrane. TTX abolished the CAP leaving a residual negative potential without altering the summating potential (SP) or the cochlear microphonic (CM). The residual potential retained its polarity when recorded from scala vestibuli. The peak latency, amplitude, and tuning properties of the residual potential showed features similar to the CAP. Application of kainic acid to the RW membrane eliminated the residual potential, leaving the SP and CM unaltered. It is hypothesized that the sources of the residual potential are the excitatory post-synaptic potentials from the peripheral processes of afferent dendrites under the inner hair cells.     

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.     

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.     

Asynchronous neural activity recorded from the round window

Voltage recorded from an electrode on the round window (RW) of guinea pig has characteristics that reflect the activity of auditory-nerve fibers in the absence of acoustic stimulation. Fast Fourier transformation (FFT) of the noise recorded from the RW electrode shows a broad spectral peak from 0.8-1.0 kHz. The magnitude of the biological noise is increased by high-frequency, bandlimited acoustic noise stimulation. Pure tones can suppress or enhance the spectral components around 0.8-1.0 kHz depending on frequency and intensity. Kainic acid applied to the intact RW membrane eliminates the biological noise (and the evoked cochlear whole-nerve responses) without alteration of the cochlear microphonic or the summating potential. The spectral characteristics of the biological noise seem to be related to the elemental waveform contributed by the individual auditory-nerve fibers to the voltage recorded at the RW electrode [Kiang et al., Electrocochleography, edited by R. J. Ruben, C. Elbering, and G. Solomon (University Park, Baltimore, 1976)].     

Postnatal development of cochlear microphonic and compound action potentials in a precocious species, Chinchilla lanigera

The development of sound-evoked responses in Chinchilla lanigera was studied from postnatal ages P0-1 (first 24 h) to adult. Cochlear microphonic (CMs) and compound action potentials (CAPs), representing ensemble sound-evoked activities of hair cells and auditory nerve fibers, respectively, were present as early as age P0-1. The data indicate that CM thresholds and sensitivities were generally adult-like (i.e., fall into adult ranges) at birth, but suprathreshold CM amplitudes remained below adult ranges through P28. CAP thresholds reached adult-like values between P7-P14, but the suprathreshold CAP amplitude continued to increase until ～P28. The results confirm the auditory precociousness of the chinchilla.     

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.     

Psychophysical estimates of level-dependent best-frequency shifts in the apical region of the human basilar membrane

It is now undisputed that the best frequency (BF) of basal basilar-membrane (BM) sites shifts downwards as the stimulus level increases. The direction of the shift for apical sites is, by contrast, less well established. Auditory nerve studies suggest that the BF shifts in opposite directions for apical and basal BM sites with increasing stimulus level. This study attempts to determine if this is the case in humans. Psychophysical tuning curves (PTCs) were measured using forward masking for probe frequencies of 125, 250, 500, and 6000 Hz. The level of a masker tone required to just mask a fixed low-level probe tone was measured for different masker-probe time intervals. The duration of the intervals was adjusted as necessary to obtain PTCs for the widest possible range of masker levels. The BF was identified from function fits to the measured PTCs and it almost always decreased with increasing level. This result is inconsistent with most auditory-nerve observations obtained from other mammals. Several explanations are discussed, including that it may be erroneous to assume that low-frequency PTCs reflect the tuning of apical BM sites exclusively and that the inherent frequency response of the inner hair cell may account for the discrepancy.     

Medial olivocochlear efferent inhibition of basilar-membrane responses to clicks: evidence for two modes of cochlear mechanical excitation

Conceptualizations of mammalian cochlear mechanics are based on basilar-membrane (BM) traveling waves that scale with frequency along the length of the cochlea, are amplified by outer hair cells (OHCs), and excite inner hair cells and auditory-nerve (AN) fibers in a simple way. However, recent experimental work has shown medial-olivocochlear (MOC) inhibition of AN responses to clicks that do not fit with this picture. To test whether this AN-initial-peak (ANIP) inhibition might result from hitherto unrecognized aspects of the traveling-wave or MOC-evoked inhibition, MOC effects on BM responses to clicks in the basal turns of guinea pig and chinchilla cochleae were measured. MOC stimulation inhibited BM click responses in a time and level dependent manner. Inhibition was not seen during the first half-cycle of the responses, but built up gradually, and ultimately increased the responses' decay rates. MOC stimulation also produced small phase leads in the response wave forms, but had little effect on the instantaneous frequency or the waxing and waning of the responses. These data, plus recent AN data, support the hypothesis that the MOC-evoked inhibitions of the traveling wave and of the ANIP response are separate phenomena, and indicate that the OHCs can affect at least two separate modes of excitation in the mammalian cochlea.     

Differentiation of cochlear pathophysiology in ears damaged by salicylate or a pure tone using a nonlinear systems identification technique.

Mongolian gerbils were exposed to either alpha-ketoglutarate, salicylate, or an 8-kHz pure tone. Cochlear microphonic (CM) was recorded from the round window in response to 68 and 88 dB SPL Gaussian noise. A nonlinear systems identification technique provided the frequency-domain parameters of a third-order polynomial model characterizing cochlear mechano-electric transduction (MET). A series of physiologic indices were derived from further exploration of the model. Exposure to the 8-kHz pure tone and round window application of salicylate resulted in different changes in the polynomial parameters and physiologic indices even though the threshold shifts were similar. A general reduction of CM magnitude was found after the tone exposure, and an increase at low-mid frequencies was demonstrated in the salicylate group especially at the lower signal level. The slope of the MET curve was reduced by the acoustic overstimulation. The root or the operating point of the MET was shifted in opposite directions after the two treatments. Sound-pressure levels that saturate MET expanded in the tone exposure group and narrowed in the salicylate group. The signal level also had effects on these indices.     

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 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.     

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.     

Frequency-dependent self-induced bias of the basilar membrane and its potential for controlling sensitivity and tuning in the mammalian cochlea

A displacement-sensitive capacitive probe technique was used in the first turn of guinea pig cochleas to examine whether the motion of the basilar membrane includes a displacement component analogous to the dc receptor potentials of the hair cells. Such a "dc" component apparently exists. At a given location on the basilar membrane, its direction toward scala vestibuli (SV) or scala tympani (ST) varies systematically with frequency of the acoustic stimulus. Furthermore, it appears to consist of two parts: a small asymmetric offset response to each gated tone burst plus a progressive shift of the basilar membrane from its previous position. The mean position shift is cumulative, increasing with successive tone bursts. The amplitude of the immediate offset response, when plotted as a function of frequency, appears to exhibit a trimodal pattern. This displacement offset is toward SV at the characteristic frequency (CF) of the location of the probe, while at frequencies either above or below the CF the offset is relatively larger, and toward ST. The mechanical motion of the basilar membrane therefore appears to contain the basis for lateral suppression. The cumulative mean position shift, however, appears to peak toward ST at the apical end of the traveling wave envelope and appears to be associated with a resonance, not of the basilar membrane motion directly, but coupled to it. The summating potential, measured concurrently at the round window, shows a more broadly tuned peak just above the CF of the position of the probe. This seems to correspond to the peak at the CF of the mechanical bias. As the preparation deteriorates, the best frequency of the vibratory displacement response decreases to about a half-octave below the original CF. There is a corresponding decrease in the frequency of the peaks of the trimodal pattern of the asymmetric responses to tone bursts. The trimodal pattern also broadens. In previous experiments the basilar membrane has been forced to move in response to a low-frequency biasing tone. The sensitivity to high-frequency stimuli varies in phase with the biasing tone. The amplitudes of slow movement in these earlier experiments and in the present experiments are of the same order of magnitude. This suggests strongly that the cumulative shift toward ST to a high-frequency acoustic stimulus constitutes a substantial controlling bias on the sensitivity of the cochlea in that same high-frequency region. Its effect will be to reduce the slope of neural rate-level functions on the high-frequency side of CF.     

The detection of increments and decrements is not facilitated by abrupt onsets or offsets

Two experiments measured thresholds for the detection of increments and decrements in the intensity of a quasi-continuous broadband-noise (experiment 1) or increments in a 477-Hz pure-tone pedestal (experiment 2). A variety of onset and offset ramps for the intensity change were tested, from instantaneous onsets or offsets to ramps lasting several tens of milliseconds. For increments and decrements with equal duration, the characteristics of the ramps had little effect on performance. Abrupt rise times, which are associated with strong transient responses in auditory neurons, did not facilitate detection in comparison to much slower rise times. The temporal window model of temporal resolution provided a good account of the data when the decision statistic was the maximum magnitude of the change in the output of the window produced by the increment or decrement, but provided a poor account of the data when the decision statistic was the maximum rate of change in the output of the window over time. Overall the results suggest that, in the absence of cues in the audio-frequency domain, rapid changes in envelope contribute little to near-threshold increment or decrement detection.     

Distinguishing cochlear pathophysiology in 4-aminopyridine and furosemide treated ears using a nonlinear systems identification technique

To test the adequacy of physiologic indices derived from a third-order polynomial model quantifying cochlear mechano-electric transduction (MET), 24 Mongolian gerbils were exposed to either 250-mM glucose (control), 150-mM 4-aminopyridine (4-AP), or 30-mM furosemide solutions applied to the round window (RW) membrane. The cochlear microphonic (CM) was recorded from the RW in response to 68- and 88-dB SPL Gaussian noise. A nonlinear systems identification technique (NLID) provided the frequency-domain parameters and physiologic indices of the polynomial model of MET. The control group showed no change in both compound action potential (CAP) thresholds and CM. Exposure to 4-AP and furosemide resulted in a similar elevation in CAP thresholds and a reduction in CM. However, the polynomial model of MET showed different changes. The operating point, slope, and symmetry of the MET function, the polynomial model parameters, and related nonlinear coherences differed between the experimental groups. It is concluded that the NLID technique is sensitive and specific to alterations in the cochlear physiology.     

Coding of spectral fine structure in the auditory nerve. II: Level-dependent nonlinear responses

Phase-locked discharge patterns of single cat auditory-nerve fibers were analyzed in response to complex tones centered at fiber characteristic frequency (CF). Signals were octave-bandwidth harmonic complexes defined by a center frequency F and an intercomponent spacing factor N, such that F/N was the fundamental frequency. Parameters that were manipulated included the phase spectrum, the number of components, and the intensity of the center component. Analyses employed Fourier transforms of period histograms to assess the degree to which responses were synchronized to the frequencies present in the acoustic stimulus. Several nonlinearities were observed in the response as intensity was varied between threshold and 80-90 dB SPL. Response nonlinearities were strong for all signals except those with random phase spectra. The most commonly observed nonlinearity was an emphasis of one or more stimulus components in the response. The degree of nonlinearity usually increased with intensity and signal complexity and decreased with fiber frequency selectivity. Half-wave rectification introduced synchronization to the missing fundamental. The strength of the response at the fundamental was related to stimulus crest factor. Signals with low center frequencies and high crest factors often elicited instantaneous discharge rates at the theoretical maximum of pi CF. This suggests that the probability of spike generation approaches one during high-amplitude waveform segments. Response nonlinearity was interpreted as arising from three sources, namely, cochlear mechanics, compression of instantaneous discharge rate, and saturation of average discharge rate. At near-threshold intensities, fibers with high spontaneous rates exhibited responses that were linear functions of stimulus waveshape, whereas fibers with low spontaneous spike rates produced responses that were best described in terms of an expansive nonlinearity.     

Setting up an experimental apparatus for the study of multimodal acoustic propagation with turbulent mean flow

An experiment has been set up to study multimodal acoustic propagation inside a cylindrical duct in presence of a turbulent mean flow. This paper describes the preliminary work which has been found necessary for assembling the experiment together with first measurement results. In order to set up this experimental facility, a high level acoustic source was developed to generate higher propagating modes in the presence of mean flow. A microphonic antenna was designed for detecting the propagating modes. LDV measurements were performed and synchronous detection was used to extract both the mean flow and the acoustic components of the particle velocity. Results of aeraulic measurements are presented. Then, results of acoustic velocity measurements are compared to results obtained from the microphonic antenna.     

Resonant double excitation observed in the near-threshold evolution of the photoexcited F K alpha satellite intensity in NaF

We present a precise measurement of the photoexcited F K alpha satellite intensity's evolution for NaF from [1s2p] double excitation threshold to saturation. A direct comparison between the observed evolution and the x-ray absorption spectrum was successfully made, and the contribution of multielectron transitions to the absorption spectrum was clearly resolved for the first time. A resonance-like feature observed in the near-threshold evolution is attributed to the [1s2p]3p(2) resonant double excitation as confirmed by calculations.