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Further studies on the mechanics of the cochlear partition in the mustached bat. II. A second cochlear frequency map derived from acoustic distortion products.

It has been proposed that acoustic 2f1-f2 distortions reflect the frequency characteristics of a secondary cochlear filter mechanism (Brown et al., 1992; Allen and Fahey, 1993). This concept was used to construct a second cochlear frequency map that may represent aspects of tectorial membrane (TM) tuning. Within the frequency range of 15-105 kHz, for a given f2 frequency, f1 was varied and the frequency ratio f2/f1 determined that produced maximum levels of the 2f1-f2 distortion (best ratio). The second cochlear frequency map was derived by plotting the distortion frequency that corresponded to the best ratio f2/f1 against the cochlear place of f2 which was obtained from the HRP-frequency map of Pteronotus (Kössl and Vater, 1985b). Minimum best ratios of 1.0005 and hence practically identical characteristic frequencies of the putative tuning of basilar membrane (HRP) and TM (2f1-f2) were found at about 45% distance from the base, a point at which 62 kHz are represented on the BM. This frequency is associated with strong cochlear resonance and large evoked and spontaneous otoacoustic emissions. Between 45% and 20% distance from the base, the basilar membrane (BM) tuning progressively increases to about 70 kHz whereas the calculated TM tuning remains constant at a frequency close to 62 kHz. The range of constant TM tuning coincides with the sparsely innervated cochlear region of Pteronotus where BM thickness is maximal and TM mass and limbal attachment are reduced (Vater and Kössl, 1996). We suggest that here the TM oscillates strongly at 62 kHz and may carry most of the energy of cochlear resonance which is transferred into movement of the organ of Corti at and apical to the 45% location where the BM is tuned to 62 kHz.

Acoustic Stimulation↗

The influence of evoking stimulus level on the neural suppression of transient evoked otoacoustic emissions.

This study concerns the suppression of transient evoked otoacoustic emissions (TEOAEs) by contralateral noise. The suppression is interpreted as neurally induced changes in cochlear mechanics. The magnitude of TEOAE suppression is explored in response to a single level of contralateral noise, in 20 normal subjects, and as a function of TEOAE evoking stimulus power in 6 subjects. TEOAE were found to be relatively more susceptible to contralateral suppression when the TEOAE evoking stimulus was low. This suggests that saturation of the TEOAE generator by the evoking stimulus reduces the susceptibility of the generator to neural suppression. However, this relation did not hold between ears. Those ears in which the TEOAE seemed easier to saturate were easier to suppress by contralateral noise. We have concluded that TEOAE generators can differ in their susceptibility to neural suppression. Ears in which the TEOAE generating mechanism is less dependent on the ipsilateral evoking stimuli power level, are also naturally more susceptible to efferent suppression.

Acoustic Stimulation↗

Intensity-dependent peak shift in cochlear transfer functions at the cellular level, its elimination by sound exposure, and its possible underlying mechanisms.

Our systematic study of cochlear transfer functions has confirmed earlier results that, in a normal cochlea, the cochlear AC responses at any given cochlear location do not have a fixed best frequency at which the response is maximal. The best frequency depends on sound intensity, shifting to lower frequencies as the intensity is increased. This phenomenon may account for the so called 'half-octave shift' of maximum cochlear damage relative to the frequency of the damaging sound observed in studies of auditory noise exposure. Our experimental results combined with the results of others and with our model studies bring us to the conclusion that, at low to moderate sound intensities, the dependence of the best frequency on sound intensity is due to an effect of the active feedback, which decreases as sound intensity increases. Consequently, the feedback, when present, must shift the best frequency upward.

Acoustic Stimulation↗

Temporal patterns of the responses of auditory-nerve fibers to low-frequency tones.

The temporal response patterns of auditory-nerve fibers to low-frequency tones were studied in anesthetized cats using period histograms. 'Peak-splitting' was observed mostly in fibers with lower characteristic frequencies (CF < 2 kHz) and with lower-frequency stimulation (< or = 500 Hz). The occurrence of peak-splitting, the number of peaks, and the time between the peaks were all dependent upon the stimulus frequency. The phases of responses, although complex functions of stimulus frequency, intensity, and the fiber's CF, clearly showed traveling-wave characteristics for all frequencies at or above 100 Hz. The amount of phase change with intensity was generally small for lower-frequency stimuli (< approximately 50 degrees), although larger phase changes (e.g., approximately 180 degrees) were occasionally seen with higher-frequency stimuli. At 50 and 100 Hz, the phase of neural responses in the basal region roughly corresponds to the maximum velocity of the basilar membrane towards scala tympani (as inferred from cochlear microphonic recordings).

Acoustic Stimulation↗

Cochlear microphonic changes after noise exposure and gentamicin administration during sleep and waking.

These experiments were designed to investigate the effect of noise, sleep, and gentamicin on the cochlear microphonic (CM) of the guinea pigs. Are the changes observed due to intrinsic cochlear phenomena or to efferent system actions? To answer this question, noise exposure together with efferent system blockade by gentamicin administration was performed. In the normal (non-treated) animal, noise exposure decreased both variability and amplitude of the tone evoked CM in about the first 10 min while the physiological modulation of slow wave sleep increasing the CM is not present. Following administration of gentamicin, noise no longer affect the CM in about the first 10 min, although it produces amplitude and variability increments. The influence of slow wave sleep on the CM is not altered. Thus, gentamicin does not block the CM sleep/wakefulness related shifts. The data were discussed in terms of the influence of gentamicin on the olivo-cochlear bundle. It was hypothesized that the effects of noise on the CM is a result of both peripheral and central influences.

Animals↗

Delayed-onset temporary auditory threshold shift following head blow in guinea pigs.

This study attempts to investigate the development of sensorineural hearing loss following a head blow without skull fracture in association with physiological and histopathologic changes in an experimental animal model. With the head in a freely movable position, albino guinea pigs were given a single blow to the occipital region by a head blow device. At 1, 7, and 14 days after the blow, the animals' auditory brainstem response (ABR) and cochlear microphonics (CM) were examined, and both the temporal bone and brain stem were observed by light and electron microscopy. The ABR threshold was unchanged at day 1, was significantly increased at day 7, and was fully recovered at day 14. The I-V and I-II interpeak latencies were significantly prolonged at days 1 and 7, and wave I latency was significantly prolonged at day 7 only. These latencies were recovered to normal limits at day 14. On the other hand, no significant change in CM versus the control group was observed at any point in the measurements. Histopathologically, no abnormal finding was seen at the light microscopic level. However, at the electron microscopic level, there were some injuries to the eighth nerve. At day 1, the lamellar structure of the myelin sheath was irregular, and the periaxonal space was expanded; at day 7, the myelin sheath was disintegrated. At day 14, however, these changes were partially reversed. These results suggest that sensorineural hearing loss following a head blow in this model is attributed to dysfunction of the eighth nerve rather than to cochlear impairment.

Animals↗

ATP-gamma-S shifts the operating point of outer hair cell transduction towards scala tympani.

ATP receptor agonists and antagonists alter cochlear mechanics as measured by changes in distortion product otoacoustic emissions (DPOAE). Some of the effects on DPOAEs are consistent with the hypothesis that ATP affects mechano-electrical transduction and the operating point of the outer hair cells (OHCs). This hypothesis was tested by monitoring the effect of ATP-gamma-S on the operating point of the OHCs. Guinea pigs anesthetized with urethane and with sectioned middle ear muscles were used. The cochlear microphonic (CM) was recorded differentially (scala vestibuli referenced to scala tympani) across the basal turn before and after perfusion (20 min) of the perilymph compartment with artificial perilymph (AP) and ATP-gamma-S dissolved in AP. The operating point was derived from the cochlear microphonics (CM) recorded in response low frequency (200 Hz) tones at high level (106, 112 and 118 dB SPL). The analysis procedure used a Boltzmann function to simulate the CM waveform and the Boltzmann parameters were adjusted to best-fit the calculated waveform to the CM. Compared to the initial perfusion with AP, ATP-gamma-S (333 microM) enhanced peak clipping of the positive peak of the CM (that occurs during organ of Corti displacements towards scala tympani), which was in keeping with ATP-induced displacement of the transducer towards scala tympani. CM waveform analysis quantified the degree of displacement and showed that the changes were consistent with the stimulus being centered on a different region of the transducer curve. The change of operating point meant that the stimulus was applied to a region of the transducer curve where there was greater saturation of the output on excursions towards scala tympani and less saturation towards scala vestibuli. A significant degree of recovery of the operating point was observed after washing with AP. Dose response curves generated by perfusing ATP-gamma-S (333 microM) in a cumulative manner yielded an EC(50) of 19.8 microM. The ATP antagonist PPADS (0.1 mM) failed to block the effect of ATP-gamma-S on operating point, suggesting the response was due to activation of metabotropic and not ionotropic ATP receptors. Multiple perfusions of AP had no significant effect (118 and 112 dB) or moved the operating point slightly (106 dB) in the direction opposite of ATP-gamma-S. Results are consistent with an ATP-gamma-S induced transducer change comparable to a static movement of the organ of Corti or reticular lamina towards scala tympani.

Adenosine Triphosphate↗

Effects of prolonged noise exposure in chinchillas with severed middle ear muscles.

Using the round window-recorded cochlear microphonic as the index of acoustic reflex activity, we noted a decay in the strength of middle ear muscle contraction in the chinchilla following an eight hour exposure to octave band noise (500 Hz. center frequency, 95 dB. sound pressure level). On the basis of this observation it was concluded that the prolonged exposure reduced the effectiveness of the acoustic reflex in protecting the cochlea. This reduction, however, may have been underestimated if the exposure was also sufficient to reduce cochlear output. The present investigation examined this possibility by comparing the effects of a similar exposure in chinchillas with intact (normal) and severed middle ear muscles. Following exposure, the cochlear microphonic magnitude increased slightly in the normal group. Decreases in the cochlear microphonic were observed in the animals with severed muscles even when the overall exposure level was reduced to simulate the effects of middle ear muscle contraction. These findings indicate that although the muscles did afford some degree of protection to the cochlea during the exposure, the protective effects of the acoustic reflex may have been reduced even beyond our original observations.

Animals↗

Effects of hyperosmotic solutions on endolymphatic pressure.

Hydrostatic pressure changes in endolymph as well as perilymph and cerebrospinal fluid (CSF) following intravenous injection of glycerol, urea, and mannitol were studied in the guinea pig using a servo-controlled micropipet system. After the initial rise in pressure observed during and immediately after injection of each hyperosmotic agent, all pressures fell below baseline levels for about 20 minutes. The largest reductions in pressure with each of the hyperosmotics showed no significant difference between CSF and labyrinth. In the glycerol and urea studies, labyrinthine pressures stabilized at their minimum levels 20 to 40 minutes after injection, while CSF pressure recovered slowly. However, alteration of labyrinthine pressures induced by mannitol paralleled that of CSF. These results may suggest a possible osmotic dehydration effect in the labyrinth for glycerol and urea, but an ambiguous effect for mannitol.

Animals↗

Histological effects of co-administration of an ACTH((4-9)) analogue, ORG 2766, on cisplatin ototoxicity in the albino guinea pig.

Cisplatin is one of the most potent antineoplastic drugs presently known, but its therapeutic efficacy is seriously limited by several side effects such as ototoxicity. Several compounds that are known for their nephroprotective effects also seem to reduce the incidence and severity of cisplatin-induced ototoxicity. Hamers et al. (1994) and De Groot et al. (1997) investigated the possibly protective effect of concomitant administration of the ACTH((4-9)) analogue ORG 2766 upon cisplatin ototoxicity in guinea pigs. Animals were treated with cisplatin at a daily dose of 2.0 mg/kg for 8 consecutive days and ORG 2766 at a daily dose of 75 mcg/kg for 9 days. Concomitant administration of cisplatin plus ORG 2766 resulted in a bimodal distribution of the electrophysiological data (compound action potential and cochlear microphonics amplitudes) and the histological data (outer hair cell (OHC) counts). It was surmised that this dichotomy might occur at a certain cisplatin dose. We investigated whether this protective effect of ORG 2766 could be enhanced by reducing the daily dose of cisplatin while maintaining the same dose of ORG 2766. Thirty-six animals were treated with daily i.p. injections of cisplatin at a dose of 1.0 mg/kg (n=18) or 1.5 mg/kg (n=18) for 8 consecutive days. When comparing the mean OHC counts of the different experimental groups, treatment with cisplatin at a daily dose of 1.5 mg/kg for 8 consecutive days resulted in a considerable loss of OHCs, which was significantly reduced after co-administration of ORG 2766. Co-treatment with ORG 2766 did not result in a change in the volume of the scala media. The present results are in agreement with the electrophysiological results published earlier (Stengs et al., 1998b).

Adrenocorticotropic Hormone↗

Characterizing non-linearity in the cochlear microphonic using the instantaneous frequency.

In this paper, we examine the non-linearity of mechano-electric transduction in the cochlea by computing the instantaneous frequency (IF) of the cochlear microphonic (CM) in response to sinusoidal stimuli. In contrast to a linear system which yields a constant IF when driven with a sinusoid, the IF of the CM varied during one period of oscillation. This variation was not symmetric, but differed for positive and negative slopes of the CM. Administration of tetrodotoxin to eliminate neural activity indicated that the variation of the IF was not due to neural contamination. Moreover, comparing the IF of the stimulus to that of the CM indicated that the IF was not due to non-linearity in the acoustic signal. Signal frequency, signal level and acoustic trauma altered the IF. A cochlear model of the CM was developed to determine the influence of the saturation of hair-cell receptor currents and vector summation on the IF. Results indicated that these factors could not fully account for the variation in the IF. We conclude that the variation in IF within one period of cochlear partition vibration indicates that the mechanical and/or electrical oscillations which produce the CM differ from those of a linear system.

Acoustic Stimulation↗

Hydrops in the cochlea can be induced by sound as well as by static pressure.

The Reissner's membrane (RM) was visualised by confocal microscopy in the isolated temporal bone of the guinea pig. The function of the organ was followed by measuring its physiological response. Static pressure applied in the basal coil caused a distention of the RM in the apical coil into the scala vestibuli. The sensitivity to a test tone was reduced. When the pressure was relieved, the RM returned to its original position and the response recovered. If the increased pressure was maintained, the RM would bulge further. The RM could then be reversibly stretched and return gradually, with a delay, to its original position. Alternatively, it could be over-stretched and return with an over-shoot past its original position toward the organ of Corti. In response to repetitive tone pulses of above 80 dB, hydrops of the RM also developed. This was accompanied by a reduced sensitivity. A slow recovery to the original position, or over-shoot, and return of responsiveness could be seen. Above 106 dB sustained loss was generally seen. It is concluded that the RM can accommodate increased scala media pressure by distention. This will relieve the organ of Corti from part of the pressure and may protect the organ from trauma.

Animals↗

Electrically evoked otoacoustic emissions from the chicken ear.

The outer hair cell electromotile response is believed to underlie the sharp tuning and exquisite sensitivity of the mammalian inner ear, and contribute to the production of electrically evoked otoacoustic emissions (EEOAEs) and sound-evoked otoacoustic emissions (OAEs). Avian ears are also sharply tuned, extremely sensitive and generate spontaneous and sound-evoked OAEs, but avian hair cells do not exhibit somatic electromotility. However, stereocilia bundle movements have been observed in avian and amphibian hair cells suggesting that EEOAEs might arise from electrically evoked bundle movements. Here, we demonstrate for the first time that AC current applied to the round window of the chicken evokes EEOAE of up to 18 dB SPL. The EEOAE produces a bandpass response with maximum amplitude in the 1000-3000 Hz range; the response drops off rapidly above 4000 Hz and below 500 Hz. The impulse response to current pulses is characterized by a large peak sometimes followed by a damped oscillation with a frequency around 2000 Hz. EEOAEs decreased significantly after anoxia and paraformaldehyde damage of the cochlea. Kanamycin-induced hair cell loss also caused a significant reduction in EEOAE and distortion product OAE; these emissions showed only a small recovery at long recovery times, when most hair cells should have regenerated. These results suggest that the EEOAE has a biological origin in the cochlea, which could presumably involve electrically evoked stereocilia bundle movements.

Animals↗

The middle ear of gekkonoid lizards: interspecific variation of structure in relation to body size and to auditory sensitivity.

Wishing to assess the effects of the dimensions of the middle ear on the auditory sensitivity of gekkonoid lizards, we measured middle ear components in preserved geckos, which in life had yielded 'cochlear microphonics' audiograms. We examined two to seven specimens of 14 species. The measures of middle ear elements varied relative to head or body length similarly within species and among species. The areas of the external ear opening, tympanic membrane, and columellar footplate, and the ratio between the last two ('hydraulic lever'), were correlated with animal length. The hydraulic and mechanical (extracolumellar) lever ratios appeared to complement each other, the former being emphasized in large animals, the latter in small animals. The apparent auditory sensitivity correlated with the sizes of the animal, head and external ear opening, and negatively (insignificantly) correlated with the mechanical lever ratio. The correlation of sensitivity with the hydraulic lever was insignificant, perhaps due to a 'tympanic membrane lever' (catenary effect). The most sensitive frequency negatively correlated with the area of the external ear opening, the area of the tympanic membrane, and with the level of greatest sensitivity. It was positively correlated with the relative length of the cartilaginous portion of the ossicular chain. However, the number of hair cells in the basilar papilla, too, is known to correlate with animal size. Moreover, the least sensitive species were not only the smallest species, they were also the species known to lack a zone of unidirectional hair cells in the basilar papilla. Hence the apparent sensitivity hypothetically depends on both middle ear dimensions and summation of inner ear output. This hypothesis requires verification by other methods.

Animals↗

The influence of inner hair cell loss on the instantaneous frequency of the cochlear microphonic.

The cochlear microphonic (CM) is produced by a change in standing currents during the motion of the cochlear partition. The motion of the partition and associated hair cell transduction processes are nonlinear and are reflected in the variation of the instantaneous frequency (IF) of the CM. Although the CM is dominated from receptor currents from outer hair cells (OHCs), receptor currents from inner hair cells (IHCs) may contribute to the fluctuation in the IF. In this paper we examine the influence of IHCs on the variation of the IF of the CM. A 75 mg/kg intraperitoneal (i.p.) dose of carboplatin reduced the IHC population by approximately 40%. The reduction in IHCs did not substantially affect the amplitude of the CM. The amplitude of the IF, however, was reduced at high signal levels (90 and 100 dB peak SPL). A phenomenological model of the CM indicated that the contribution of IHC receptor currents to the IF was small and that changes in OHC transducer characteristics may have a greater impact on the IF.

Acoustic Stimulation↗

Effects of conductive hearing loss on temporal aspects of sound transmission through the ear.

Effects of conductive hearing loss on level and spectrum are well known. However, little is known about possible additional effects on temporal aspects of sound transmission. This study investigated effects of earplugs and middle ear effusions on amplitude and timing of cochlear microphonic (CM) responses in gerbils. Bilateral CM responses to pure tones (1-16 kHz) were monitored before and after (i). unilateral earplug insertion or (ii). injection of silicone oil, of various viscosities, into one middle ear. Earplugs produced flat hearing losses (mean 13 dB) and delayed CMs more at lower (mean 80 micros, 1-6 kHz) than at higher (20 micros, 8-16 kHz) frequencies. Effusions also produced flat hearing loss. On average, high viscosity effusions produced larger hearing losses (36 dB) than medium (25 dB) or low (20 dB) viscosity effusions. Low and medium viscosity effusions delayed responses to lower (mean 82 and 65 micros respectively, 1-6 kHz) more than to higher (mean 20 and 10 micros respectively, 8-16 kHz) frequencies. High viscosity effusions produced smaller delays across all frequencies (mean 31 micros, 1-16 kHz). In normal animals, CM responses were not delayed over a wide range of stimulus levels. Therefore, in addition to attenuation, conductive loss distorts acoustic temporal cues important for hearing.

Animals↗

Sound-evoked efferent effects on cochlear mechanics of the mustached bat.

The influence of the crossed medial efferent system on cochlear mechanics of the mustached bat was tested by measuring delayed evoked otoacoustic emissions (DEOAEs), cochlear microphonics, distortion product otoacoustic emissions (DPOAEs) and stimulus frequency otoacoustic emissions. Contralaterally delivered sinusoids, broadband noise and bat echolocation calls were used for acoustic stimulation of the efferent system. With all four measures we found a level-dependent suppression under stimulation with both broadband noise and echolocation calls. In addition, the sharply tuned cochlear resonance of the mustached bat which is involved in processing echolocation signals at 61 kHz shifted upward in frequency by several 100 Hz. Presentation of sinusoids did not have any significant effect. DEOAEs and DPOAEs were in some cases enhanced during contralateral presentation of the bat calls at moderate intensities. The most important function of the efferent system in the mustached bat might be the control of the extraordinarily fine-tuned resonator of this species, which is close to instability as evident from the very pronounced evoked otoacoustic emissions which sometimes convert into spontaneous otoacoustic emissions of high level.

Acoustic Stimulation↗