Correlation of changes in compound action potential (CAP) tuning curves and cochlear lesion in guinea pigs after explosion

The purpose of the present study was to investigate the sensitivity of compound action potential (CAP) tuning curves to changes of the cochlear status in guinea pigs after explosion and their ability to reflect specific histological variations. The results were as follows: 1. The CAP tuning curves were abnormally broad and the Q 10 dB values were reduced by a factor of 1 after explosion, indicating wider tuning. 2. The degree of broadening of the CAP tuning curves seemed to increase as the hair cell loss increased. 3. After explosion, the tip of the tuning curve shifted to frequencies significantly higher or lower than that of the signal, it might be related to the location of hair cell loss in the cochlea. 4. In animals for which damage was restricted to only three rows of outer hair cells, changes of the CAP tuning curves were observed. It provides further evidence that the tuning properties of cochlear nerve fibers are dependent upon the integrity of the outer hair cells even though the great majority of fibers innervate inner hair cells only.     

The inner ear as an electrosensory sense organ]

A model for cochlear perception is introduced based on the consideration that the organ of Corti is an electrosensory organ like that found in fish physiology during phylogenetic development. The inner hair cells work as electroreceptors, the outer hair cells as electrocytes. A layer of potassium ions on the lower surface of the tectorial membrane causes the excitation of the inner hair cells as soon as contact with a stereocilium occurs. A model for the basilar membrane motion, based on mathematical considerations and in accordance with the typical tuning curves of single auditory nerve fibres can serve as basis to explain the results of frequency and intensity analyses if we assume an electric excitation of the inner hair cells.     

A model of the generation of the cochlear microphonic with nonlinear hair cell transduction and nonlinear basilar membrane mechanics

A phenomenological model of the generation of the cochlear microphonic of the guinea pig is presented which incorporates sharp tuning and nonlinear growth of the vibration of the cochlear partition, and nonlinear transduction of this response by a single linear array of hair cells (assumed to be the outer hair cells). The contribution to the microphonic potential from each hair cell generator is also assumed to decay exponentially with distance from the hair cell. Using experimentally obtained estimates for the parameters a good agreement between the theoretical microphonic tuning curves and growth functions was obtained without recourse to complex micromechanical motion of the cochlear partition, electrical tuning of the hair cells or a contribution from the inner hair cells of the cochlea.     

Intratympanic ototoxicity: influence of post-injection survival period

Many studies have been reported on the intratympanic ototoxicity of different drugs in animal models. The recovery periods of the animals following intratympanic drug applications varied among these studies. The present study compares the cochlear damage caused by intratympanic kanamycin following short (4 days) and long (30 days) post-injection survival periods, using the guinea pig as the animal model. The degree of cochlear damage 4 days after kanamycin injection was consistent among the tested animals. The degeneration was mainly confined to the outer hair cells and almost all inner hair were spared. The change 30 days after kanamycin injection was more variable among the animals and both inner and outer hair cells were damaged. This shows that, although the damage to the cochlea after intratympanic aminoglycoside injection is progressive, a short post-injection recovery period is suitable for comparative intratympanic ototoxicity studies.     

Auditory nerve fibre responses to salicylate revisited

Ototoxicity of salicylate is accompanied by a temporary hearing loss and tinnitus and has therefore been used to study tinnitus in animal models. Salicylate induced elevated central auditory activity has been interpreted as a correlate of tinnitus. Whether this elevated activity in the central auditory system is due to an increased activity in the auditory nerve is still under discussion. To explore this issue, we recorded the activity of single auditory nerve fibres in anaesthetised gerbils following systemic injection of salicylic acid. Firstly, compound action potential (CAP) thresholds were determined at 5-0 min intervals. Fifteen to 30 min after 200 mg/kg salicylic acid, threshold loss developed in the high frequency range. At 2 h CAP threshold loss reached a plateau amounting to 15-20 dB above 16 kHz, 0-5 dB below 2 kHz. An almost immediate start of threshold loss was observed after 400 mg/kg salicylic acid. A plateau of threshold loss was reached after 1.5 h with values of 25 dB in the high, 5-10 dB in the low frequency range. Secondly, responses of single auditory nerve fibres were studied after administration of 200 mg/kg salicylic acid. Frequency tuning curves and rate intensity (RI) functions at characteristic frequency (CF) were measured. Two hours and more after application, single fibre thresholds were elevated by about 20 dB at all CFs. Sharpness of tuning was reduced. Mean spontaneous rate was significantly reduced at CFs below 5 kHz (mean: 44 vs 28 AP/s). At CFs above 5 kHz mean spontaneous rate remained unchanged. In RI functions no change in maximum discharge rate was observed. The altered response properties can be interpreted by the known effects of salicylate on the prestin mediated active process of the outer hair cells. The elevated activity in the central auditory system after salicylate intoxication thus cannot be caused by cochlear nerve hyperactivity.     

铅暴露对豚鼠耳蜗毛细胞损害的定量分析

目的研究铅暴露浓度与豚鼠耳蜗毛细胞形态学改变和对听觉系统损害程度的量化关系。方法50只豚鼠分为对照组和实验组。对照组(10只)豚鼠腹腔注射生理盐水1ml,隔日一次。实验组分为两组:高铅组(20只):豚鼠腹腔注射0.25%醋酸铅溶液40mg/kg;低铅组(20只):豚鼠腹腔注射0.25%醋酸铅溶液20mg/kg,分别于停药后7、14、28天采血。断头后行全耳蜗铺片的光学和电镜检查。结果腹腔注射醋酸铅后,血清中铅含量迅速升高。低铅组铅暴露1周后出现外毛细胞损害;高铅组铅暴露2周后外毛细胞损害程度较重,出现细胞变性、减少、结构不清,电镜观察可见毛细胞缺失明显;高铅暴露4周后毛细胞损害呈进行性加重。结论铅暴露对豚鼠耳蜗毛细胞损害明显,表现为纤毛的散乱、倒伏、部分脱落、大片缺失等,其损害程度与铅暴露浓度呈正相关性。     

Tonotopic evolution during development

The evolution of cochlear tonotopy can be observed by the study of the modification of tuning curves as obtained from auditory nerve fibers in the kitten. The differential development of the two components of the tuning curves, i.e. the tail, which is restricted to lower frequencies that appear at first during ontogenesis, and the tip which is restricted to higher frequencies that appear later, can explain the ontogenetic variations of tonotopy observed in the past. An hypothesis is presented where the tail of the tuning curve is related to the first functioning of the basal inner hair cells during development, whereas the delayed appearance of the tip is related to the basal outer hair cells. The base-apex gradient of maturation of receptors, along with their lateral gradient of development can explain the tonotopic shift observed during the cochlear ontogenesis.     

Filter function of the guinea pig cochlea after degeneration of outer hair cells

After kanamycin induced degeneration of outer hair cells from guinea pigs the tuning properties of primary auditory nerve fibres are compared with those of normal untreated guinea pigs. The existence of fibres with no alteration of the tuning properties leads to the conclusion that there is no neural interaction between inner and outer hair cells needed to enhance the frequency selectivity.     

Hidden cochlear impairments

Pure tone audiometry is a routine clinical examination used to identify hearing loss. A normal pure tone audiogram is usually taken as evidence of normal hearing. Auditory deficits detected in subjects with normal audiograms, such as poor sound discrimination and auditory perceptual disorders, are generally attributed to central problems. Does the pure tone audiogram truly reflect cochlear status? Recent evidence suggests that individuals with normal audiogram may still have reduced peripheral auditory responses but normal central responses, indicating that the pure tone audiometry may not detect some types of cochlear injuries. In the cochlea, the outer hair cells (OHCs), inner hair cells (IHCs), and the spiral ganglion neurons that synapse with IHCs are the 3 key cochlear components in transducing acoustical vibrations into the neural signals. This report reviews three types of cochlear damage identified in laboratory animals that may not lead to overt hearing loss. The first type of cochlear impairment, such as missing a certain proportion of IHCs without damage to OHCs, may reduce the cochlear output and elevate response threshold; however, the reduced peripheral auditory sensitivity may be restored along the auditory pathway via central gain enhancement. The second type of cochlear impairment, such as selective damage to the synapses of the high-threshold thin auditory nerve fibers (ANFs), reduces cochlear output at high stimulation levels with no effect on response threshold. In this case the reduced cochlear output may be compensated along the auditory pathway as well. The third type of cochlear impairment, such as missing a certain number of OHCs without damage to others, may not even affect cochlear function at all. These “hidden” cochlear impairments do not result in overt hearing loss, but they may increase the vulnerability of the cochlea to traumatic exposure and lead to disrupted central auditory processing.     

Noise-induced degeneration in the brain and representation of inner and outer hair cells

Noise that destroys receptor cells in the chinchilla cochlea also results in degeneration of axonal endings in the brain from the cochlear nerve fibers and the auditory pathways ascending to the superior olivary complex and inferior colliculus. The patterns of degeneration provide experimental evidence for differential representation of inner and outer hair cells and their functions.     

cis-diamminedichloroplatinum cochlear toxicity

Twenty-nine guinea pigs were divided into three groups. The first group received distilled water 2 ml/kg ip daily; the second group received DDP 2 mg/kg ip daily; and the third group DDP 4 mg/kg ip daily. ABR hearing threshold was tested before injection. Twenty-four hours after systemic administration, ABR hearing threshold was tested again. The animals were killed and the cochlear specimens were observed under light, scanning and transmission electron microscopes. No abnormality regarding ABR hearing threshold and cochlear morphology was observed in the first group. In the second group, ABR hearing threshold was elevated, inner and outer hair cells, supporting cells, striae vascularis and spiral ganglions were damaged. In the third group, ABR hearing threshold elevated markedly. All above-mentioned cells were severely damaged. The experiment showed that the cochlear damage induced by DDP was dose related. The severest damage was seen in the second turn of the cochlea. The damage to the Deiters' cells was earliest and severest. The outer hair cells were more vulnerable to the damage than the inner hair cells did.     

Some current concepts of cochlear mechanics

The development of the current concepts is reviewed in historical perspective. Helmholtz's hypothesis of basilar-membrane resonance was partially confirmed and partially defeated by Békésy's experiments on models and postmortem cochlear preparations. He discovered that sound was propagated in the cochlea in the form of traveling waves which reached a flat maximum at a frequency-dependent location. Mathematical theory explained this type of sound propagation as a special case of surface waves. Johnstone and his coworkers discovered that the maximum of cochlear vibration in living animals was much sharper than postmortem, and more recently Khanna and Johnstone independently determined the maximum to be nearly as sharp as the tuning curves of the inner hair cells and the auditory-nerve fibers. These findings, together with the work at the Massachusetts Institute of Technology on alligator lizards, have led to new concepts of cochlear mechanics which include hypothesized micromechanical processes in the organ of Corti. These concepts deal not only with the sharpness of basilar-membrane tuning but also with the details of the basilar-membrane amplitude and phase characteristics, as well as with the hair cell and neural tuning curves and response phases. They suggest that some sharpening of the tuning curves occurs between the basilar membrane and hair-cell responses. Such sharpening has been demonstrated in lizards, but in the mammalian ear, the relation is less clear.     

Filter function of the guinea pig cochlea after degeneration of outer hair cells

Summary After kanamycin induced degeneration of outer hair cells from guinea pigs the tuning properties of primary auditory nerve fibres are compared with those of normal untreated guinea pigs. The existence of fibres with no alteration of the tuning properties leads to the conclusion that there is no neural interaction between inner and outer hair cells needed to enhance the frequency selectivity.This study was supported by the Deutsche Forschungsgemeinschaft (Bo 421/1-3). Kanamycin was kindly provided by Chemie Grünenthal.     

Absence of Voltage-Dependent Compliance in High-Frequency Cochlear Outer Hair Cells

Cochlear outer hair cells are the key element in a mechanical amplification process that enhances auditory sensitivity and tuning in the mammalian inner ear. The electromotility of outer hair cells, that is, their ability to extend or contract at acoustic frequencies, is proposed to be the source of the mechanical amplification. For amplification to take place, some stiffness is required for outer hair cells to communicate force to the organ of Corti, the sensory epithelium of the inner ear. Modulation of this stiffness would be expected to have a significant effect on inner ear function. Outer hair cell compressive stiffness has recently been shown to be dependent on membrane potential, but this has only been demonstrated for cells originating in the apical, low-frequency segment of the cochlea, whereas cochlear amplification is arguably more important in the more basal high-frequency segment. The voltage-dependent compliance (the reciprocal of stiffness) of high-frequency outer hair cells was investigated by two methods in cells isolated from the basal turns of the guinea pig cochlea. In contrast to previous findings, no evidence was found for voltage-dependent changes in compliance. The results call into question the importance of outer hair cell voltage-dependent compliance as a component of cochlear amplification.     

Neuronal responses in the inferior colliculus of mutant mice (Bronx waltzer) with hereditary inner hair cell loss

Bronx waltzer mice lose a great proportion of their cochlear inner hair cells during early development. Hair cell counts revealed that these mice lacked on average 86% of their inner hair cells. Outer hair cells were present in a normal number, but appeared disarranged. The effect of this inner hair cell loss on the properties of central auditory neurons was investigated by recording neuronal responses in the inferior colliculus. Neuronal thresholds were on average elevated by 40 dB compared to CBA controls. The frequency tuning curves of the mutants were broad, and in part (18.5%) multi-peaked. The tonotopy found in the inferior colliculus of the Bronx waltzer mice appeared diffuse. Both the driven and spontaneous discharge rates were not statistically significantly different from the controls. However, the average first spike latency was significantly longer in the Bronx waltzer mice.     

Aspartate aminotransferase immunoreactivity in cochlea of guinea pig

The distribution of aspartate aminotransferase-like immunoreactivity in the cochlea of the guinea pig was studied at the light microscopy level. Indirect immunofluorescence histochemistry using antisera against cytoplasmic aspartate aminotransferase prepared from pig heart was applied to surface preparations of the organ of Corti and cryostat sections of the cochlea. In the modiolus, immunofluorescence was localized to spiral ganglion cells and myelinated fibers of the auditory nerve and intraganglionic spiral bundles. In the organ of Corti, immunofluorescence was seen in upper tunnel crossing fibers and at the base of outer hair cells, following a distribution similar to that of the efferent innervation of the outer hair cells. Weak immunofluorescence was seen in the inner spiral bundle and tunnel spiral bundle, but was not present in all preparations. Immunofluorescence was not seen in inner hair cells, nor at the base of inner hair cells, and may have been absent from outer hair cells.It is concluded that spiral ganglion cells and myelinated auditory nerve axons contain aspartate aminotransferase-like immunoreactivity; such immunoreactivity has previously been determined in auditory nerve endings in the cochlear nucleus. Olivocochlear neurons that innervate outer hair cells also contain such immunoreactivity while other cochlear efferents contain little or none.     

Spiral Ligament Pathology: A Major Aspect of Age-Related Cochlear Degeneration in C57BL/6 Mice

Data from systematic, light microscopic examination of cochlear histopathology in an age-graded series of C57BL/6 mice (1.5-15 months) were compared with threshold elevations (measured by auditory brain stem response) to elucidate the functionally important structural changes underlying age-related hearing loss in this inbred strain. In addition to quantifying the degree and extent of hair cell and neuronal loss, all structures of the cochlear duct were qualitatively evaluated and any degenerative changes were quantified. Hair cell and neuronal loss patterns suggested two degenerative processes. In the basal half of the cochlea, inner and outer hair cell loss proceeded from base to apex with increasing age, and loss of cochlear neurons was consistent with degeneration occurring secondary to inner hair cell loss. In the apical half of the cochlea with advancing age, there was selective loss of outer hair cells which increased from the middle to the extreme apex. A similar gradient of ganglion cell loss was noted, characterized by widespread somatic aggregation and demyelination. In addition to these changes in hair cells and their innervation, there was widespread degeneration of fibrocytes in the spiral ligament, especially among the type IV cell class. The cell loss in the ligament preceded the loss of hair cells and/or neurons in both space and time suggesting that fibrocyte pathology may be a primary cause of the hearing loss and ultimate sensory cell degeneration in this mouse strain.     

卡铂对灰鼠中枢听觉系统的影响

目的 卡铂选择性破坏灰鼠的内毛细胞和Ⅰ型传入神经末梢已被人们所证实,但是,卡铂是否损害耳蜗核、下丘和听觉皮层还不清楚,本文旨在观察卡铂对灰鼠听觉中枢的毒性作用。方法采用恒低温冷冻连续脑组织切片,以中枢听觉系统神经元的密度来评价卡铂对灰鼠中枢听觉系统的影响。结果发现注射卡铂3和4周后,耳蜗背侧核和腹侧核神经元明显的减少,与正常动物比较有显著性差异。而下丘和听觉皮层神经元的变化与正常灰鼠比较无明显差异。结论 说明注射卡铂3和4周后对耳蜗核有明显的毒性作用,可引起耳蜗核神经元明显的减少,但是,对灰鼠下丘和听皮层未见明显的毒性作用。     

Recovery of threshold shift in hair-cell stereocilia following exposure to intense stimulation

The isolated cochlear coil preparation was used to study changes in hair-cell stereocilia stiffness before and after overstimulation. Results were obtained from inner and outer hair cells in the apical and middle turns of the guinea pig cochlea. The stereocilia bundles were stimulated with an oscillating water jet and their movements were identified with stroboscopic illumination in a differential interference contrast microscope. The intensity of the water jet could be varied in decibel steps and the attenuation needed to achieve a 'visual detection level' threshold of movement was the criterion response throughout. Pre-exposure thresholds were sampled, the stereocilia bundle was overstimulated, and thresholds were measured during a recovery interval. Sensory hair bundles on all hair-cell rows showed a loss in stiffness following overstimulation which was proportional to the impedance of the stereocilia bundle. During recovery, stiffness increased and often showed a return to the pre-exposure threshold level. The results demonstrated that the loss of sensory hair stiffness following overstimulation recovered with the passage of time. The magnitude of the initial threshold shift, however, was related to the exposure conditions, cochlear location, and the impedance of the sensory hair bundle. The rate of recovery appeared to be independent of cochlear location, hair-cell row, or exposure conditions.     

The clinical utility of distortion-product otoacoustic emissions

Otoacoustic emissions permit, for the first time, an unbiased means of examining the preneural elements of the peripheral auditory pathway that make the initial contribution to the perception of acoustic stimuli. Distortion-product otoacoustic emissions (DPOAEs) represent one type of evoked emission that has significant potential for becoming an important test in the audiometric evaluation of hearing capacity. In the present review, selected examples of several forms of sensorineural hearing loss demonstrate that DPOAEs have the ability to act as objective indicators of the frequency/level configuration of the conventional audiogram in cases in which hearing impairment results primarily from damage to the outer hair cells. In contrast, normal DPOAE functioning, in the presence of a significant hearing loss, indicates a locus of damage central to the region of the outer hair cells. Like the other emitted responses, DPOAEs can be measured noninvasively, are highly repeatable, under test-retest conditions, and are simple and rapid to detect using microcomputer-based instrumentation. Further, DPOAEs test both the "threshold" and suprathreshold levels of outer hair-cell activity in the form of response/growth functions, over a 30- to 40-dB stimulus range. In combination, these attributes indicate that DPOAEs can provide an objective and comprehensive assessment of the cochlear reserve of a given ear.