Some aspects of temporal coding by single cochlear fibres from regions of cochlear hair cell degeneration in the guinea pig

Summary Some temporal coding properties of cochlear nerve fibres are investigated in kanamycin-treated guinea pigs (GPs) with various degrees of outer hair cell (OHC) degeneration. In particular, the phase locking ability of fibres from pathological cochleas, and also their adaptation properties are compared with the properties of normal cochlear fibres. No systematic effects of OHC loss on these properties have so far been found.These preliminary results therefore suggest (in so far as these animals can be regarded as models of sensorineural hearing loss of cochlear origin in man) that little deterioration should be expected in functions purely dependent upon faithful temporal coding of the stimulus waveform.     

Assessment of auditory nonlinearity for listeners with different hearing losses using temporal masking and categorical loudness scaling

A dysfunction or loss of outer hair cells (OHC) and inner hair cells (IHC), assumed to be present in sensorineural hearing-impaired listeners, affects the processing of sound both at and above the listeners' hearing threshold. A loss of OHC may be responsible for a reduction of cochlear gain, apparent in the input/output function of the basilar membrane and steeper-than-normal growth of loudness with level (recruitment). IHC loss is typically assumed to cause a level-independent loss of sensitivity. In the current study, parameters reflecting individual auditory processing were estimated using two psychoacoustic measurement techniques. Hearing loss presumably attributable to IHC damage and low-level (cochlear) gain were estimated using temporal masking curves (TMC). Hearing loss attributable to OHC (HL(OHC)) was estimated using adaptive categorical loudness scaling (ACALOS) and by fitting a loudness model to measured loudness functions. In a group of listeners with thresholds ranging from normal to mild-to-moderately impaired, the loss in low-level gain derived from TMC was found to be equivalent with HL(OHC) estimates inferred from ACALOS. Furthermore, HL(OHC) estimates obtained using both measurement techniques were highly consistent. Overall, the two methods provide consistent measures of auditory nonlinearity in individual listeners, with ACALOS offering better time efficiency.     

豚鼠冲击波负压暴露后耳蜗毛细胞损害定量观察

目的 探讨冲击波负压（blast underpressure,BUP）暴露后豚鼠耳蜗毛细胞损害特点.方法将豚鼠暴露实验性BUP 14天后处死,硝酸银染色硬铺片法计数观察耳蜗基底膜毛细胞损伤情况.结果压力峰值介于-22.4kPa和-63.3kPa之间的实验性BUP暴露后,豚鼠耳蜗外毛细胞出现了明显的病理性改变,损伤的程度以第二转最重,第二排和第三排的病变比第一排更为严重.BUP强度越高,毛细胞损害越重.各实验组动物的外毛细胞总缺失率明显高于正常对照组（P＜0.01）;重复暴露3次的动物外毛细胞缺失率明显高于暴露1次的动物（P＜0.01）.结论BUP暴露可引起明显的豚鼠耳蜗外毛细胞缺失等损害,其损害程度与负压峰值及暴露次数密切相关;毛细胞损害越重,ABR阈移也就越明显.     

Response of the cochlear nucleus neurons of the cat to tone-burst-trains

Although both posteroventral cochlear nucleus (PVCN) and dorsal cochlear nucleus (DCN) are innervated by the descending branch of auditory nerve fibers, their intrinsic morphological organizations are so different that their physiological roles are expected to be different in signal processing. Temporal information coding of acoustic signals in the cochlear nucleus was examined by using stimuli of "tone-burst-trains (TBT)". Responses of cochlear nucleus neurons of anesthetized cats were recorded either intracellularly or extracellularly. Responses of the neurons to TBT stimuli were classified into "adaptive type" and "non-adaptive type". The "adaptive type" neurons were mainly recorded from PVCN. Responses of these neurons to TBT stimuli decayed exponentially, because of short-term adaptation, in the subsequent tone-bursts. These neurons faithfully preserve the adaptative behavior of auditory nerve fibers. On the contrary, the "non-adaptive type" neurons were mainly found in DCN. They showed variety of responses to TBT stimuli including facilitation, disinhibition and inhibition depending on duration and/or interval of tone-bursts. Our results suggest that some "non-adaptive type" neurons, showing facilitative and/or inhibitory responses to TBT stimuli, act as temporal filters that extract temporal information from acoustic signals.     

Candidate's thesis: enhancing intrinsic cochlear stress defenses to reduce noise-induced hearing loss

OBJECTIVES/HYPOTHESIS: Oxidative stress plays a substantial role in the genesis of noise-induced cochlear injury that causes permanent hearing loss. We present the results of three different approaches to enhance intrinsic cochlear defense mechanisms against oxidative stress. This article explores, through the following set of hypotheses, some of the postulated causes of noise-induced cochlear oxidative stress (NICOS) and how noise-induced cochlear damage may be reduced pharmacologically. 1) NICOS is in part related to defects in mitochondrial bioenergetics and biogenesis. Therefore, NICOS can be reduced by acetyl-L carnitine (ALCAR), an endogenous mitochondrial membrane compound that helps maintain mitochondrial bioenergetics and biogenesis in the face of oxidative stress. 2) A contributing factor in NICOS injury is glutamate excitotoxicity, which can be reduced by antagonizing the action of cochlear -methyl-D-aspartate (NMDA) receptors using carbamathione, which acts as a glutamate antagonist. 3) Noise-induced hearing loss (NIHL) may be characterized as a cochlear-reduced glutathione (GSH) deficiency state; therefore, strategies to enhance cochlear GSH levels may reduce noise-induced cochlear injury. The objective of this study was to document the reduction in noise-induced hearing and hair cell loss, following application of ALCAR, carbamathione, and a GSH repletion drug D-methionine (MET), to a model of noise-induced hearing loss. STUDY DESIGN: This was a prospective, blinded observer study using the above-listed agents as modulators of the noise-induced cochlear injury response in the species chinchilla langier. METHODS: Adult chinchilla langier had baseline-hearing thresholds determined by auditory brainstem response (ABR) recording. The animals then received injections of saline or saline plus active experimental compound starting before and continuing after a 6-hour 105 dB SPL continuous 4-kHz octave band noise exposure. ABRs were obtained immediately after noise exposure and weekly for 3 weeks. After euthanization, cochlear hair cell counts were obtained and analyzed. RESULTS ALCAR administration reduced noise-induced threshold shifts. Three weeks after noise exposure, no threshold shift at 2 to 4 kHz and <10 dB threshold shifts were seen at 6 to 8 kHz in ALCAR-treated animals compared with 30 to 35 dB in control animals. ALCAR treatment reduced both inner and outer hair cell loss. OHC loss averaged <10% for the 4- to 10-kHz region in ALCAR-treated animals and 60% in saline-injected-noise-exposed control animals. Noise-induced threshold shifts were also reduced in carbamathione-treated animals. At 3 weeks, threshold shifts averaged 15 dB or less at all frequencies in treated animals and 30 to 35 dB in control animals. Averaged OHC losses were 30% to 40% in carbamathione-treated animals and 60% in control animals. IHC losses were 5% in the 4- to 10-kHz region in treated animals and 10% to 20% in control animals. MET administration reduced noise-induced threshold shifts. ANOVA revealed a significant difference (P <.001). Mean OHC and IHC losses were also significantly reduced (P <.001). CONCLUSIONS: These data lend further support to the growing body of evidence that oxidative stress, generated in part by glutamate excitotoxicity, impaired mitochondrial function and GSH depletion causes cochlear injury induced by noise. Enhancing the cellular oxidative stress defense pathways in the cochlea eliminates noise-induced cochlear injury. The data also suggest strategies for therapeutic intervention to reduce NIHL clinically.     

Classification of unit types in the anteroventral cochlear nucleus of laboratory mice

This report introduces a system for the objective physiological classification of single-unit activity in the anteroventral cochlear nucleus (AVCN) of anesthetized CBA/129 and CBA/CaJ mice. As in previous studies, the decision criteria are based on the temporal properties of responses to short tone bursts that are visualized in the form of peri-stimulus time histograms (PSTHs). Individual unit types are defined by the statistical distribution of quantifiable metrics that relate to the onset latency, regularity, and adaptation of sound-driven discharge rates. Variations of these properties reflect the unique synaptic organizations and intrinsic membrane properties that dictate the selective tuning of sound coding in the AVCN. When these metrics are applied to the mouse AVCN, responses to best frequency (BF) tones reproduce the major PSTH patterns that have been previously demonstrated in other mammalian species. The consistency of response types in two genetically diverse strains of laboratory mice suggests that the present classification system is appropriate for additional strains with normal peripheral function. The general agreement of present findings to established classifications validates laboratory mice as an adequate model for general principles of mammalian sound coding. Nevertheless, important differences are noted for the reliability of specialized endbulb transmission within the AVCN, suggesting less secure temporal coding in this high-frequency species.     

Gamma-aminobutyric acidergic and glycinergic inputs shape coding of amplitude modulation in the chinchilla cochlear nucleus.

Amplitude modulation is a prominent acoustic feature of biologically relevant sounds, such as speech and animal vocalizations. Enhanced temporal coding of amplitude modulation signals is found in certain dorsal and posteroventral cochlear nucleus neurons when they are compared to auditory nerve. Although mechanisms underlying this improved temporal selectivity are not known, involvement of inhibition has been suggested. gamma-Aminobutyric acid- and glycine-mediated inhibition have been shown to shape the dorsal cochlear nucleus and posteroventral cochlear nucleus response properties to other acoustic stimuli. In the present study, responses to amplitude modulation tones were obtained from chinchilla dorsal cochlear nucleus and posteroventral cochlear nucleus neurons. The amplitude modulation carrier was set to the neuron's characteristic frequency and the modulating frequency varied from 10 Hz. Rate and temporal modulation transfer functions were compared across neurons. Bandpass temporal modulation transfer functions were observed in 74% of the neurons studied. Most cochlear nucleus neurons (90%) displayed flat or lowpass rate modulation transfer functions to amplitude modulation signals presented at 2540 dB (re: characteristic frequency threshold). The role of inhibition in shaping responses to amplitude modulation stimuli was examined using iontophoretic application of glycine or gamma-aminobutyric acidA receptor agonists and antagonists. Blockade of gamma-aminobutyric acidA or glycine receptors increased stimulus-evoked discharge rates for a majority of neurons tested. Synchronization to the envelope was reduced, particularly at low and middle modulating frequencies, with temporal modulation transfer functions becoming flattened and less bandpass in appearance. Application of glycine, gamma-aminobutyric acid or muscimol increased the modulation gain over the low- and mid-modulation frequencies and reduced the discharge rate across envelope frequencies for most neurons tested. These findings support the hypothesis that glycinergic and gamma-aminobutyric acidergic inputs onto certain dorsal cochlear nucleus and posteroventral cochlear nucleus neurons play a role in shaping responses to amplitude modulation stimuli and may be responsible for the reported preservation of amplitude modulation temporal coding in dorsal cochlear nucleus and posteroventral cochlear nucleus neurons at high stimulus intensities or in background noise.     

Consequences of noise- or styrene-induced cochlear damages on glutamate decarboxylase levels in the rat inferior colliculus

Both noise and styrene can injure the cochlea, resulting in a reduction of incoming inputs from the cochlea to the central nervous system. In addition, styrene is known to have neurotoxic properties at high doses. The loss of inputs caused by noise has been shown to be compensated by a new equilibrium between excitatory and inhibitory influences within the inferior colliculus (IC). The main goal of this study was to determine whether styrene-induced hearing loss could also be counterbalanced by a GABAergic adjustment in the IC. For this purpose, rats were exposed to noise (97 dB SPL octave band noise centered at 8 kHz), or to a non-neurotoxic dose of styrene for 4 weeks (700 ppm, 6 h/day, 5 days/week). Auditory sensitivity was tested by evoked potentials, and cochlear damage was assessed by hair cell counts. Glutamate decarboxylase (GAD) was dosed in the IC by indirect competitive enzyme-linked immunosorbent assay. Both noise and styrene caused PTSs that reached 27.0 and 14.6 dB respectively. Outer hair cell (OHC) loss caused by noise did not exceed 9% in the first row, on the other hand OHC loss induced by styrene reached 63% in the third row. Only the noise caused a decrease of GAD of 37% compared to that measured in the controls. No significant modification of GAD concentration has been shown after styrene exposure. Thus, central compensation for cochlear damage may depend on the nature of the ototoxic agent. Unless styrene directly affects IC function, it is reasonable to assume that noise causes a modification of inhibitory neurotransmission within the structure because of impairment of afferent supply to the auditory brainstem. The present findings suggest that central compensation for cochlear damage can preferably occur when afferent fibers are altered.     

A cochlear model using feedback from motile outer hair cells

A model of cochlear vibrations based upon motile outer hair cells (OHCs) has been developed using physiologically demonstrated phenomena. Rapid longitudinally directed OHC forces are connected in such a way as to form a negative-feedback system. The responses at the higher frequencies (greater than 1 kHZ) are quite realistic: they have properly shaped amplitude curves with large tip-to-tail ratios (30-50 dB), Q10's of 2-6, and 'shoulders' at frequencies an octave below the resonant frequency. The phases are also quite realistic, though asymptoting at somewhat lower values (about -6 pi radians) than observed physiologically. The responses in the apical section are not so realistic. The form of the OHC force is physically unrealizable, but realizable forms are discussed.     

DPOAE in tinnitus patients with cochlear hearing loss considering hyperacusis and misophonia

The most probable place generating tinnitus in auditory pathway are outer hair cells (OHC) inside cochlea. To asses their activity otoacoustic emission is used. The goal of the investigation was estimation the features of otoemission DPOAE in groups with tinnitus patients with cochlear hearing loss, estimation of diagnostic value of DPOAE parameters for analysis of function of the cochlea in investigated patients emphasizing DPOAE parameters most useful in localizing tinnitus generators and estimation of hypothetic influence of hyperacusis and misophony on parameters of DPOAE in tinnitus patients with cochlear hearing loss. The material of the study were 42 tinnitus patients with cochlear hearing loss. In the control group there were 21 patients without tinnitus with the same type of hearing loss. Then tinnitus patients were divided into three subgroups--with hyperacusis, misophony and without both of them, based on audiologic findings. METHOD: after taking view on tinnitus and physical examination in all the patients pure tone and impedance audiometry, supratreshold tests, ABR and audiometric average and discomfort level were evaluated. Then otoemission DPOAE was measured in three procedures. First the amplitudes of two points per octave were assessed, in second--"fine structure" method-- 16-20 points per octave (f2/f1 = 1.2, L1 = L2 = 70 dB). Third procedure included recording of growth rate function in three series for input tones of value f2 = 2002, 4004, 6006 Hz (f2/f1= 1.22) and levels L1=L2, growing by degrees of 5dB in each series. RESULTS: DPOAE amplitudes in recording of 2 points per octave and fine structure method are very valuable parameters for estimation of cochlear function in tinnitus patients with cochlear hearing loss. Decreasing of DPOAE amplitudes in patients with cochlear hearing loss and tinnitus suggests significant role of OHC pathology, unbalanced by IHC injury in generation of tinnitus in patients with hearing loss of cochlear localization. DPOAE fine structure provides us the additional information about DPOAE amplitude recorded in two points per octave, spreading the amount of frequencies f2, where differences are noticed in comparison of two groups--tinnitus patients and control. Function growth rate cannot be the only parameter in estimation of DPOAE in tinnitus patients with cochlear hearing loss, also including subjects with hyperacusis and misophony. Hyperacusis has important influence on DPOAE amplitude, increases essentially amplitude of DPOAE in the examined group of tinnitus patients.     

Relation between outer hair cell loss and hearing loss in rats exposed to styrene

The relationship between outer hair cell (OHC) loss and cochlear sensitivity is still unclear, because in many animal models there exist surviving but dysfunctional OHCs and also injured/dead inner hair cells (IHC). Styrene is an ototoxic agent, which targets and destroys OHCs starting from the third row to the second and first rows depending on the exposure level. The remaining cells may be less affected. In this experiment, rats were exposed to styrene by gavage at different doses (200-800mg/kg/day) for varying periods (5 days/week for 3-12 weeks). An interesting finding was that the cochlear sensitivity was not affected in a few rats with all OHCs in the third row being destroyed by styrene. A further loss of OHCs was usually accompanied with a linear input/output (I/O) function of cochlear compound action potentials (CAP), indicating the loss of cochlear amplification. However, normal CAP amplitudes at the highest stimulation level of 90dB SPL were often observed when all OHCs were destroyed, indicating normal function of the remaining IHCs. The OHC-loss/hearing-loss relation appeared to be a sigmoid-type function. Initially, styrene-induced OHC losses (<33%) did not result in a significant threshold shift. Then CAP threshold shift increased dramatically with OHC loss from 33% to 66%. Then, CAP threshold changed less with OHC loss. The data suggest a tri-modal relationship between OHC loss and cochlear amplification. That is, under the condition that all surviving OHCs are ideally functioning, the cochlear amplifier is not affected until 33% of OHCs are absent, then the gain of the amplifier decreases proportionally with the OHC loss, and at last the amplifier may fail completely when more than 67% of OHCs are lost.     

Effects of 4-aminopyridine on electrically evoked cochlear emissions and mechano-transduction in guinea pig outer hair cells.

Stimulation of the cochlea with alternating current produces sound in the ear canal. These electrically evoked oto-acoustic emissions (EEOAEs) are attributed to electro-motility of outer hair cells (OHCs). Earlier work suggested EEOAEs were sensitive to the open probability of OHC mechano-electrical transduction (MET) channels. They were attenuated by 4-aminopyridine (4-AP) and amplitude-modulated by low frequency sound, consistent with current gaining access to a motility source via the MET conductance. However, inconsistencies in the behaviour as well as physical considerations argued against this simple interpretation. In this study the behaviour of EEOAEs in the presence of 4-AP in scala media was examined along with OHC transfer functions derived from low frequency cochlear microphonic (CM) waveforms. Both the level and the modulation of the EEOAEs were reduced by 4-AP, but disproportionately more so than the 4-AP-induced loss of CM. In addition, the modulation as well as the level of the EEOAEs recovered more rapidly than the CM. Both these results indicated that 4-AP modified the process of EEOAE generation independently of its effect on the gross receptor current through the MET conductance. Changes in the derived OHC transfer functions, specifically shifts in the estimated operating bias of the MET channels, indicated the effects of 4-AP applied to the endolymphatic surface of OHCs were complex. It is suggested that both direct and indirect consequences of a 4-AP blockade may have contributed. 4-AP was ineffective when applied to scala tympani.     

The functional age of hearing loss in a mouse model of presbycusis. II. Neuroanatomical correlates

This report relates patterns of age-related outer hair cell (OHC) loss to auditory behavioral deficits in C57BL/6J mice. Hair cell counts were made from serial sections of the cochlear partition in three subject groups representing young (2-3 months), middle (8-9 months), and old ages (12-13 months). The cochlear location of OHC counts was determined from three-dimensional computerized reconstructions of the serial sections. Comparisons of the topographic distribution of surviving OHCs across the subject groups confirmed an orderly base-to-apex progression of cochlear degeneration that is well known in this mouse strain. All mice appeared to follow the same progression of OHC loss, although subjects showed considerable variation in the rate at which they advanced through a uniform sequence of structural changes. Behavioral implications of the magnitude and location of OHC loss were investigated by correlating the histological status of individual mice with sound detection thresholds from the same subjects [Hear. Res. 183 (2003) 44-56]. The analysis revealed regionalized patterns of OHC loss that were correlated with frequency-dependent changes in hearing thresholds, and validates the use of 'functional age' as an indicator of age-related cochlear degeneration and dysfunction. In the absence of physiologically defined cochlear frequency maps for C57BL/6J mice, these structure-function correlation techniques offer an alternative approach for linking anatomical results to hearing abilities.     

Acute hyperpolarization and elongation of cochlear outer hair cells on superfusion with cis-platinum

The acute effects of cis-platinum on isolated cochlear outer hair cells (OHC) were investigated with whole-cell patch-clamps and measurements of cell length changes. Our findings demonstrated that cis-platinum reversibly induced a hyperpolarization and cellular elongation. These results suggest that the effects produced are the result of an interaction between cis-platinum and transduction channels in OHC. These acute effects are distinctly different from the chronic, irreversible ones that are followed by death of the OHC. The exact mechanism of these chronic effects remains unknown as yet.Presented in part at the Inner Ear Biology Workshop, August 1990, Tubingen, Germany     

Speech perception and otoacoustic emissions by pre-processing sound in the inner ear]

Direct observations of the basilar membrane movements show that sound perception can no longer be regarded as a passive process: vulnerable, energy-consuming amplification processes are required in the cochlea. The outer hair cells (OHC) fulfil this demand morphologically and functionally. These sensory cells have a double role: they perceive sound and thus modulate the cochlear biomechanics through their motile activity. The key event of sound transduction is performed by the inner hair cells (IHC) after active sound amplification in the OHC. The control of the OHC is assured by the efferent olivocochlear fibres which release acetylcholine (ACh) and gamma-aminobutyric acid (GABA) into the synaptic cleft at the basal pole of the OHC. Nicotinergic acetylcholine and GABA receptors within the outer cell membrane of OHC were identified and characterised. The application of the neurotransmitter GABA to the basal pole of vital OHC leads to a reversible elongation of the cylindrical cell body while ACh induces a reversible, slow contraction of the sensory cells. These two neurotransmitters are supposed to counteract in the control of the cochlear amplifier. The reciprocal distribution of ACh and GABA receptors and their counteracting function (contraction vs elongation) has an additional impact on the modulation of OHC function. The result is an even more diversified control of the cochlear amplifier. The energy-consuming cochlear amplifications are reflected by an epiphenomenon, i.e. the otoacoustic emissions (OAE). These are emitted by the cochlea and can be divided into "spontaneous OAE", "transitory evoked OAE" (TEOAE), "stimulus frequency OAE" and "distortion product OAE". The TEOAE are now an integrated part of audiological diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)     

A new model for calculating auditory excitation patterns and loudness for cases of cochlear hearing loss

A model for calculating auditory excitation patterns and loudness for steady sounds for normal hearing is extended to deal with cochlear hearing loss. The filters used in the model have a double ROEX-shape, the gain of the narrow active filter being controlled by the output of the broad passive filter. It is assumed that the hearing loss at each audiometric frequency can be partitioned into a loss due to dysfunction of outer hair cells (OHCs) and a loss due to dysfunction of inner hair cells (IHCs). OHC loss is modeled by decreasing the maximum gain of the active filter, which results in increased absolute threshold, reduced compressive nonlinearity and reduced frequency selectivity. IHC loss is modeled by a level-dependent attenuation of excitation level, which results in elevated absolute threshold. The magnitude of OHC loss and IHC loss can be derived from measures of loudness recruitment and the measured absolute threshold, using an iterative procedure. The model accurately fits loudness recruitment data obtained using subjects with unilateral or highly asymmetric cochlear hearing loss who were required to make loudness matches between tones presented alternately to the two ears. With the same parameters, the model predicted loudness matches between narrowband and broadband sound reasonably well, reflecting loudness summation. The model can also predict when a dead region is present.     

Effects of intense noise exposure on the outer hair cell plasma membrane fluidity

Outer hair cells (OHCs) play an important role in cochlear amplification via their length changes (electromotility). A noise-induced cochlear amplification loss leading to a permanent threshold shift (PTS) was observed without a significant hair cell loss in rats [Chen, G.D., Liu, Y., 2005. Mechanisms of noise-induced hearing loss potentiation by hypoxia. Hear. Res. 200, 1-9.]. Since motor proteins are inserted in the OHC lateral membrane, any change in the OHC plasma membrane may result in a loss of OHC electromotility, leading to a loss of cochlear amplification. In this study, the lateral diffusion in the OHC plasma membrane was determined in vitro in guinea pigs by fluorescent recovery after photobleaching (FRAP) after an in vivo noise exposure. The lateral diffusion in the OHC plasma membrane demonstrated a length-dependence, which increased as OHC length increased. A reduction in the lateral diffusion was observed in those OHCs with lengths of 50-70 microm after exposure to an 8-kHz octave band noise at 110 dB SPL for 3h. This membrane fluidity change was associated with the selective PTS at frequencies around 8 kHz. The reduction of the lateral diffusion in the OHC lateral wall indicated that noise could impair the micromechanics of the OHC lateral wall and might consequently impair OHC electromotility to induce threshold shift.     

Unitary ototoxic gentamicin exposure may not disrupt the function of cochlear outer hair cells in mice

Background: Previous study showed that mild ototoxic exposure could induce a reversible hearing impairment, and the loss and secondary incomplete recovery of cochlear ribbon synapses could be responsible for the hearing loss. However, it remains unclear whether cochlear outer hair cells’ (OHCs) functions are affected.

Objective: To verify whether the function of OHCs are also affected significantly after the ototoxic exposure.

Methods: Mice were injected intraperitoneally with 100?mg/kg concentration of gentamicin daily for 14 days. Distortion Product of Oto-acoustic Emission (DPOAE) was detected at control (pre-treatment), Day 0, day 4, day 7, day 14 and day 28 after the ototoxic exposure, respectively. In addition, the morphology of OHCs was observed by electron microscopy, OHCs has been counted by light microscopy, and the hearing thresholds were detected by auditory brain response (ABR).

Results: No significant changes have been found in OHC and OHC stereocilia among the experimental groups (p?>?.05). Further, no significant changes or loss was found in the morphology of OHCs either. However, we found ABR threshold elevations occurred after ototoxic exposure.

Conclusions: Unitary ototoxic gentamicin exposure may not disrupt the function of cochlear OHCs in mice, regardless of hearing loss identified in this ototoxic exposure.     

Chlorpromazine inhibits cochlear function in guinea pigs

Outer hair cell (OHC) electromotility provides mechanical positive feedback that functions as the cochlear amplifier. In isolated OHCs, chlorpromazine shifts the electromotility voltage-displacement transfer function in a depolarizing direction without affecting its magnitude. This study sought to measure the effects of chlorpromazine on cochlear function in vivo. Salicylate, a drug that greatly reduces the magnitude of electromotility, was used for comparison. Perilymphatic perfusion of the guinea pig cochlea with chlorpromazine or salicylate increased the compound action potential (CAP) threshold across the frequency spectrum (1-20 kHz). Both drugs also increased distortion product otoacoustic emission (DPOAE) thresholds in the higher frequencies (10-20 kHz). Complete reversibility of these effects occurred after washout. Both drugs demonstrated concentration-dependent reductions in cochlear function that followed sigmoidal curves with similar fits to previously reported results in isolated OHCs. The endolymphatic potential was not affected by either of these drugs. Thus, chlorpromazine inhibits cochlear function in a manner consistent with what would be expected from data in isolated OHCs. This suggests that shifting the electromotility transfer function correspondingly reduces the gain of the cochlear amplifier.