Activity Of Outer Hair Cells Research Articles

Outer hair cells stir cochlear fluids.

We hypothesized that active outer hair cells drive cochlear fluid circulation. The hypothesis was tested by delivering the neurotoxin, kainic acid, to the intact round window of young gerbil cochleae while monitoring auditory responses in the cochlear nucleus. Sounds presented at a modest level significantly expedited kainic acid delivery. When outer-hair-cell motility was suppressed by salicylate, the facilitation effect was compromised. A low-frequency tone was more effective than broadband noise, especially for drug delivery to apical locations. Computational model simulations provided the physical basis for our observation, which incorporated solute diffusion, fluid advection, fluid-structure interaction, and outer-hair-cell motility. Active outer hair cells deformed the organ of Corti like a peristaltic tube to generate apically streaming flows along the tunnel of Corti and basally streaming flows along the scala tympani. Our measurements and simulations coherently indicate that the outer-hair-cell action in the tail region of cochlear traveling waves is for cochlear fluid circulation.

Unraveling the molecular landscape of lead-induced cochlear synaptopathy: a quantitative proteomics analysis.

Exposure to heavy metal lead can cause serious health effects such as developmental neurotoxicity in infants, cognitive impairment in children, and cardiovascular and nephrotoxic effects in adults. Hearing loss is one of the toxic effects induced by exposure to lead. Previous studies demonstrated that exposure to lead causes oxidative stress in the cochlea and disrupts ribbon synapses in the inner hair cells. This study investigated the underlying mechanism by evaluating the changes in the abundance of cochlear synaptosomal proteins that accompany lead-induced cochlear synaptopathy and hearing loss in mice. Young-adult CBA/J mice were given lead acetate in drinking water for 28 days. Lead exposure significantly increased the hearing thresholds, particularly at the higher frequencies in both male and female mice, but it did not affect the activity of outer hair cells or induce hair cell loss. However, lead exposure decreased wave-I amplitude, suggesting lead-induced cochlear synaptopathy. In agreement, colocalization of pre- and post-synaptic markers indicated that lead exposure decreased the number of paired synapses in the basal turn of the cochlea. Proteomics analysis indicated that lead exposure increased the abundance of 352 synaptic proteins and decreased the abundance of 394 synaptic proteins in the cochlea. Bioinformatics analysis indicated that proteins that change in abundance are highly enriched in the synaptic vesicle cycle pathway. Together, these results suggest that outer hair cells are not the primary target in lead-induced ototoxicity, that lead-induced cochlear synaptopathy is more pronounced in the basal turn of the cochlea, and that synaptic vesicle cycle signaling potentially plays a critical role in lead-induced cochlear synaptopathy.

Age-related alterations in efferent medial olivocochlear-outer hair cell and primary auditory ribbon synapses in CBA/J mice.

Hearing decline stands as the most prevalent single sensory deficit associated with the aging process. Giving compelling evidence suggesting a protective effect associated with the efferent auditory system, the goal of our study was to characterize the age-related changes in the number of efferent medial olivocochlear (MOC) synapses regulating outer hair cell (OHC) activity compared with the number of afferent inner hair cell ribbon synapses in CBA/J mice over their lifespan. Organs of Corti of 3-month-old CBA/J mice were compared with mice aged between 10 and 20 months, grouped at 2-month intervals. For each animal, one ear was used to characterize the synapses between the efferent MOC fibers and the outer hair cells (OHCs), while the contralateral ear was used to analyze the ribbon synapses between inner hair cells (IHCs) and type I afferent nerve fibers of spiral ganglion neurons (SGNs). Each cochlea was separated in apical, middle, and basal turns, respectively. The first significant age-related decline in afferent IHC-SGN ribbon synapses was observed in the basal cochlear turn at 14 months, the middle turn at 16 months, and the apical turn at 18 months of age. In contrast, efferent MOC-OHC synapses in CBA/J mice exhibited a less pronounced loss due to aging which only became significant in the basal and middle turns of the cochlea by 20 months of age. This study illustrates an age-related reduction on efferent MOC innervation of OHCs in CBA/J mice starting at 20 months of age. Our findings indicate that the morphological decline of efferent MOC-OHC synapses due to aging occurs notably later than the decline observed in afferent IHC-SGN ribbon synapses.

Asymmetric vibrations in the organ of Corti by outer hair cells measured from excised gerbil cochlea

Pending questions regarding cochlear amplification and tuning are hinged upon the organ of Corti (OoC) active mechanics: how outer hair cells modulate OoC vibrations. Our knowledge regarding OoC mechanics has advanced over the past decade thanks to the application of tomographic vibrometry. However, recent data from live cochlea experiments often led to diverging interpretations due to complicated interaction between passive and active responses, lack of image resolution in vibrometry, and ambiguous measurement angles. We present motion measurements and analyses of the OoC sub-components at the close-to-true cross-section, measured from acutely excised gerbil cochleae. Specifically, we focused on the vibrating patterns of the reticular lamina, the outer pillar cell, and the basilar membrane because they form a structural frame encasing active outer hair cells. For passive transmission, the OoC frame serves as a rigid truss. In contrast, motile outer hair cells exploit their frame structures to deflect the upper compartment of the OoC while minimally disturbing its bottom side (basilar membrane). Such asymmetric OoC vibrations due to outer hair cell motility explain how recent observations deviate from the classical cochlear amplification theory.

Distortion Product Otoacoustic Emission and Tinnitus: Role of Outer Hair Cells in the Genesis of Tinnitus

Background: This study aims to detect outer hair cell (OHC) function in patients with tinnitus, by comparing the otoacoustic emissions (OAEs) in tinnitus patients with normal hearing and normal-hearing subjects without tinnitus, thereby revealing the role of OHC in the generation of tinnitus. Methods: After approval by the local research and ethics committee, this study was done in the department of otolaryngology and associated hospitals, from April 2022 to January 2023. Consent was obtained from all the participants in the present work after explaining the test procedure. The study group included 60 subjects with bilaterally normal hearing to participate. They were classified into two groups: Group 1, i.e., the control group, comprised 30 subjects who were unaffected by tinnitus, whereas Group 2, i.e., the study group, comprised 30 subjects who were suffering from tinnitus. Basic audiological tests and OAE test were done on the respondents of both the groups followed by a comparison of outcomes. Results: The authors of the present study found a statistically significant difference between the amplitude and signal-to-noise ratio (SNR) of distortion product OAE (DPOAE) in tinnitus patients and the control group without tinnitus, suggesting that OHCs have a role in the generation of tinnitus. Conclusion: It can be concluded that OHC activity was reduced in patients with tinnitus, as detected by reduced DPOAE amplitude and SNR, suggesting that the dysfunction of OHCs can be attributable to the generation of tinnitus.

Lead exposure induces nitrative stress and disrupts ribbon synapses in the cochlea.

Environmental exposure to heavy metal lead, a public health hazard in many post-industrial cities, causes hearing impairment upon long-term exposure. Lead-induced cochlear and vestibular dysfunction is well-documented in animal models. Although short-term exposure to lead at concentrations relevant to environmental settings does not cause significant shifts in hearing thresholds in adults, moderate- to low-level lead exposures induce neuronal damage and synaptic dysfunction. We reported that lead exposure induces oxidative stress in the mouse cochlea. However, lead-induced nitrative stress and potential damage to cochlear ribbon synapses are yet to be fully understood. Therefore, this study has evaluated cochlear synaptopathy and nitrative stress in young-adult mice exposed to 2 mM lead acetate for 28 days. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated that this exposure significantly increased the blood lead levels. Assessment of hair cell loss by immunohistochemistry analysis and outer hair cell (OHC) activity by recording distortion product otoacoustic emissions (DPOAEs) indicated that the structure and function of the hair cells were not affected by lead exposure. However, this exposure significantly decreased the expression of C-terminal-binding protein-2 (CtBP2) and GluA2, pre- and post-synaptic protein markers in the inner hair cell synapses, particularly in the basal turn of the organ of Corti, suggesting lead-induced disruption of ribbon synapses. In addition, lead exposure significantly increased the nitrotyrosine levels in spiral ganglion cells, suggesting lead-induced nitrative stress in the cochlea. Collectively, these findings suggest that lead exposure even at levels that do not affect the OHCs induces cochlear nitrative stress and causes cochlear synaptopathy.

Direct Cochlear Recordings in Humans Show a Theta Rhythmic Modulation of Auditory Nerve Activity by Selective Attention.

The architecture of the efferent auditory system enables prioritization of strongly overlapping spatiotemporal cochlear activation patterns elicited by relevant and irrelevant inputs. So far, attempts at finding such attentional modulations of cochlear activity delivered indirect insights in humans or required direct recordings in animals. The extent to which spiral ganglion cells forming the human auditory nerve are sensitive to selective attention remains largely unknown. We investigated this question by testing the effects of attending to either the auditory or visual modality in human cochlear implant (CI) users (3 female, 13 male). Auditory nerve activity was directly recorded with standard CIs during a silent (anticipatory) cue-target interval. When attending the upcoming auditory input, ongoing auditory nerve activity within the theta range (5-8 Hz) was enhanced. Crucially, using the broadband signal (4-25 Hz), a classifier was even able to decode the attended modality from single-trial data. Follow-up analysis showed that the effect was not driven by a narrow frequency in particular. Using direct cochlear recordings from deaf individuals, our findings suggest that cochlear spiral ganglion cells are sensitive to top-down attentional modulations. Given the putatively broad hair-cell degeneration of these individuals, the effects are likely mediated by alternative efferent pathways compared with previous studies using otoacoustic emissions. Successful classification of single-trial data could additionally have a significant impact on future closed-loop CI developments that incorporate real-time optimization of CI parameters based on the current mental state of the user.SIGNIFICANCE STATEMENT The efferent auditory system in principle allows top-down modulation of auditory nerve activity; however, evidence for this is lacking in humans. Using cochlear recordings in participants performing an audiovisual attention task, we show that ongoing auditory nerve activity in the silent cue-target period is directly modulated by selective attention. Specifically, ongoing auditory nerve activity is enhanced within the theta range when attending upcoming auditory input. Furthermore, over a broader frequency range, the attended modality can be decoded from single-trial data. Demonstrating this direct top-down influence on auditory nerve activity substantially extends previous works that focus on outer hair cell activity. Generally, our work could promote the use of standard cochlear implant electrodes to study cognitive neuroscientific questions.

Cochlear Synaptopathy due to Mutations in OTOF Gene May Result in Stable Mild Hearing Loss and Severe Impairment of Speech Perception.

Congenital profound hearing loss with preserved cochlear outer hair cell activity (otoacoustic emissions and cochlear microphonic) is the most common phenotype associated with mutations in the OTOF gene. The aim of this study was to investigate the pathophysiological mechanisms behind the auditory dysfunction in five patients (2 adults and 3 children) carrying biallelic mutations in OTOF, who showed an uncommon phenotype of mild hearing impairment associated with severe difficulties in speech perception and delay of language development. Patients underwent audiometric assessment with pure-tone and speech perception evaluation, and otoacoustic emissions and auditory brainstem response recording. Cochlear potentials were recorded in all subjects through transtympanic electrocochleography in response to clicks delivered in the free field from 120 to 60 dB peak equivalent SPL and were compared to recordings obtained from 20 normally hearing controls and from eight children with profound deafness due to mutations in the OTOF gene. Three patients out of five underwent unilateral cochlear implantation. Speech perception measures and electrically evoked auditory nerve potentials were obtained within 1 year of cochlear implant use. Pathogenic mutations in the two alleles of OTOF were found in all five patients, and five novel mutations were identified. Hearing thresholds indicated mild hearing loss in four patients and moderate hearing loss in one. Distortion product otoacoustic emissions were recorded in all subjects, whereas auditory brainstem responses were absent in all but two patients, who showed a delayed wave V in one ear. In electrocochleography recordings, cochlear microphonics and summating potentials showed normal latency and peak amplitude, consistently with preservation of both outer and inner hair cell activity. In contrast, the neural compound action potential recorded in normally hearing controls was replaced by a prolonged, low-amplitude negative response. No differences in cochlear potentials were found between OTOF subjects showing mild or profound hearing loss. Electrical stimulation through the cochlear implant improved speech perception and restored synchronized auditory nerve responses in all cochlear implant recipients. These findings indicate that disordered synchrony in auditory fiber activity underlies the impairment of speech perception in patients carrying biallelic mutations in OTOF gene who show a stable phenotype of mild hearing loss. Abnormal nerve synchrony with preservation of hearing sensitivity is consistent with selective impairment of vesicle replenishment at the ribbon synapses with relative preservation of synaptic exocytosis. Cochlear implants are effective in restoring speech perception and synchronous activation of the auditory pathway by directly stimulating auditory fibers.

Nonlinearity of intracochlear motion and local cochlear microphonic: Comparison between guinea pig and gerbil

Studying the in-vivo mechanical and electrophysiological cochlear responses in several species helps us to have a comprehensive view of the sensitivity and frequency selectivity of the cochlea. Different species might use different mechanisms to achieve the sharp frequency-place map. The outer hair cells (OHC) play an important role in mediating frequency tuning. In the present work, we measured the OHC-generated local cochlear microphonic (LCM) and the motion of different layers in the organ of Corti using optical coherence tomography (OCT) in the first turn of the cochlea in guinea pig. In the best frequency (BF) band, our observations were similar to our previous measurements in gerbil: a nonlinear peak in LCM responses and in the basilar membrane (BM) and OHC-region displacements, and higher motion in the OHC region than the BM. Sub-BF the responses in the two species were different. In both species the sub-BF displacement of the BM was linear and LCM was nonlinear. Sub-BF in the OHC-region, nonlinearity was only observed in a subset of healthy guinea pig cochleae while in gerbil, robust nonlinearity was observed in all healthy cochleae. The differences suggest that gerbils and guinea pigs employ different mechanisms for filtering sub-BF OHC activity from BM responses. However, it cannot be ruled out that the differences are due to technical measurement differences across the species.

Interactions between Passive and Active Vibrations in the Organ of Corti In Vitro

High sensitivity and selectivity of hearing require an active cochlea. The cochlear sensory epithelium, the organ of Corti, vibrates because of external and internal excitations. The external stimulation is acoustic pressures mediated by the scala fluids, whereas the internal excitation is generated by a type of sensory receptor cells (the outer hair cells) in response to the acoustic vibrations. The outer hair cells are cellular actuators that are responsible for cochlear amplification. The organ of Corti is highly structured for transmitting vibrations originating from acoustic pressure and active outer hair cell force to the inner hair cells that synapse on afferent nerves. Understanding how the organ of Corti vibrates because of acoustic pressure and outer hair cell force is critical for explaining cochlear function. In this study, cochleae were freshly isolated from young gerbils. The organ of Corti in the excised cochlea was subjected to mechanical and electrical stimulation that are analogous to acoustic and cellular stimulation in the natural cochlea. Organ of Corti vibrations, including those of individual outer hair cells, were measured using optical coherence tomography. Respective vibration patterns due to mechanical and electrical stimulation were characterized. Interactions between the two vibration patterns were investigated by applying the two forms of stimulation simultaneously. Our results show that the interactions could be either constructive or destructive, which implies that the outer hair cells can either amplify or reduce vibrations in the organ of Corti. We discuss a potential consequence of the two interaction modes for cochlear frequency tuning.

Effect of Auditory Predictability on the Human Peripheral Auditory System.

Auditory perception is facilitated by prior knowledge about the statistics of the acoustic environment. Predictions about upcoming auditory stimuli are processed at various stages along the human auditory pathway, including the cortex and midbrain. Whether such auditory predictions are processed also at hierarchically lower stages—in the peripheral auditory system—is unclear. To address this question, we assessed outer hair cell (OHC) activity in response to isochronous tone sequences and varied the predictability and behavioral relevance of the individual tones (by manipulating tone-to-tone probabilities and the human participants’ task, respectively). We found that predictability alters the amplitude of distortion-product otoacoustic emissions (DPOAEs, a measure of OHC activity) in a manner that depends on the behavioral relevance of the tones. Simultaneously recorded cortical responses showed a significant effect of both predictability and behavioral relevance of the tones, indicating that their experimental manipulations were effective in central auditory processing stages. Our results provide evidence for a top-down effect on the processing of auditory predictability in the human peripheral auditory system, in line with previous studies showing peripheral effects of auditory attention.

Auditory Neuropathy Spectrum Disorders: From Diagnosis to Treatment: Literature Review and Case Reports.

Auditory neuropathy spectrum disorder (ANSD) refers to a range of hearing impairments characterized by deteriorated speech perception, despite relatively preserved pure-tone detection thresholds. Affected individuals usually present with abnormal auditory brainstem responses (ABRs), but normal otoacoustic emissions (OAEs). These electrophysiological characteristics have led to the hypothesis that ANSD may be caused by various dysfunctions at the cochlear inner hair cell (IHC) and spiral ganglion neuron (SGN) levels, while the activity of outer hair cells (OHCs) is preserved, resulting in discrepancies between pure-tone and speech comprehension thresholds. The exact prevalence of ANSD remains unknown; clinical findings show a large variability among subjects with hearing impairment ranging from mild to profound hearing loss. A wide range of prenatal and postnatal etiologies have been proposed. The study of genetics and of the implicated sites of lesion correlated with clinical findings have also led to a better understanding of the molecular mechanisms underlying the various forms of ANSD, and may guide clinicians in better screening, assessment and treatment of ANSD patients. Besides OAEs and ABRs, audiological assessment includes stapedial reflex measurements, supraliminal psychoacoustic tests, electrocochleography (ECochG), auditory steady-state responses (ASSRs) and cortical auditory evoked potentials (CAEPs). Hearing aids are indicated in the treatment of ANSD with mild to moderate hearing loss, whereas cochlear implantation is the first choice of treatment in case of profound hearing loss, especially in case of IHC presynaptic disorders, or in case of poor auditory outcomes with conventional hearing aids.

Music and psychoacoustic perception abilities in cochlear implant users with auditory neuropathy spectrum disorder

ObjectiveAuditory neuropathy spectrum disorder (ANSD) is a condition wherein the pre-neural or cochlear outer hair cell activity is intact, but the neural activity in the auditory nerve is disrupted. Cochlear implant (CI) can be beneficial for subjects with ANSD; however, little is known about the music perception and psychoacoustic abilities of CI users with ANSD. Music perception in CI users is a multidimensional and complex ability requiring the contribution of both auditory and nonauditory abilities. Even though auditory abilities lay the foundation, the contribution of patient-related variables such as ANSD may affect the music perception. This study aimed to evaluate the psychoacoustic and music perception abilities of CI recipients with ANSD. Study designTwelve CI users with ANSD and twelve age- and gendermatched CI users with sensorineural hearing loss (SNHL) were evaluated. Music perception abilities were measured using the Turkish version of the Clinical Assessment of Music Perception (T-CAMP) test. Psychoacoustic abilities were measured using the spectral ripple discrimination (SRD) and temporal modulation transfer function (TMTF) tests. In addition, the age of diagnosis and implantation was recorded. ResultsPitch direction discrimination (PDD), timbre recognition, SRD, and TMTF performance of CI users with ANSD were concordant with those reported in previous studies, and differences between ANSD and SNHL groups were not statistically significant. However, the ANSD group performed poorly compared with SNHL group in melody recognition subtest of T-CAMP, and the difference was statistically significant. ConclusionCI can prove beneficial for patients with ANSD with respect to their music and psychoacoustic abilities, similar to patients with SNHL, except for melody recognition. Recognition of melodies requires both auditory and non-auditory abilities, and ANSD may have an extensive but subtle effect in the life of CI users.

The CAPOS mutation in ATP1A3 alters Na/K-ATPase function and results in auditory neuropathy which has implications for management.

Cerebellar ataxia, areflexia, pes cavus, optic atrophy and sensorineural hearing impairment (CAPOS) is a rare clinically distinct syndrome caused by a single dominant missense mutation, c.2452G>A, p.Glu818Lys, in ATP1A3, encoding the neuron-specific alpha subunit of the Na+/K+-ATPase α3. Allelic mutations cause the neurological diseases rapid dystonia Parkinsonism and alternating hemiplegia of childhood, disorders which do not encompass hearing or visual impairment. We present detailed clinical phenotypic information in 18 genetically confirmed patients from 11 families (10 previously unreported) from Denmark, Sweden, UK and Germany indicating a specific type of hearing impairment-auditory neuropathy (AN). All patients were clinically suspected of CAPOS and had hearing problems. In this retrospective analysis of audiological data, we show for the first time that cochlear outer hair cell activity was preserved as shown by the presence of otoacoustic emissions and cochlear microphonic potentials, but the auditory brainstem responses were grossly abnormal, likely reflecting neural dyssynchrony. Poor speech perception was observed, especially in noise, which was beyond the hearing level obtained in the pure tone audiograms in several of the patients presented here. Molecular modelling and in vitro electrophysiological studies of the specific CAPOS mutation were performed. Heterologous expression studies of α3 with the p.Glu818Lys mutation affects sodium binding to, and release from, the sodium-specific site in the pump, the third ion-binding site. Molecular dynamics simulations confirm that the structure of the C-terminal region is affected. In conclusion, we demonstrate for the first time evidence for auditory neuropathy in CAPOS syndrome, which may reflect impaired propagation of electrical impulses along the spiral ganglion neurons. This has implications for diagnosis and patient management. Auditory neuropathy is difficult to treat with conventional hearing aids, but preliminary improvement in speech perception in some patientssuggests that cochlear implantation may be effectivein CAPOS patients.

Suppression of Otoacoustic Emission using Schroeder Harmonic Complexes as Suppressing Stimuli

Introduction: Medial Olivocochlear Reflex (MOCR) causes inhibition of outer hair cell activity upon noise stimulation and acts as protective mechanism of the ear against noise. MOCR can be recorded through the suppression of Otoacoustic Emission (OAE). The mechanism of MOCR function was still unclear and whether the function is affected by the phase of incoming noise requires further investigation. This research aimed to identify the effect of MOCR activity ; i) at different frequency; ii) when using different phases of Schroeder harmonic complexes as the suppressor noise. Materials and method: Twenty six normal hearing subjects were recruited. The suppression was analysed by looking at amplitude difference of Distortion Product of Otoacoustic Emission (DPOAE) in the absence of noise and in the presence of noise in contralateral ear, at different tested frequencies (1, 1.5, 2, 3, 4, 6 kHz). Results: There was significantly higher suppression amplitude for frequency 1-2 kHz compared to higher frequencies (p<0.05). Significant higher suppression was observed when negative phase of Schroeder harmonic complexes (c: -1) was used as suppressing stimuli compared to that of positive phase (c: +1) (p<0.05). Conclusion: These findings showed that MOCR; i) is enhanced at mid-frequency region, and ii) has the ability to inhibit the outer hair cell active mechanism differently upon stimulation with different phases of noise.

Finite-element model of the nonlinear distortion and linear reflection sources of the otoacoustic emissions within the mouse cochlea

It has been hypothesized that the otoacoustic emissions (OAEs) are generated at least by two fundamental mechanisms; the nonlinear distortion and linear reflection within the cochlea. The recent studies show that different components of the organ of Corti (OoC) vibrate unsynchronized both in phase and magnitude. The difference is dramatically frequency dependent. We have developed and validated a finite-element model of the mouse cochlea against two sets of measurement at the cochlear base and apex. The nonlinear distortion and linear reflections have been implemented in the model- the former one by the active outer hair cells (OHCs) and the later one by introducing the impedance irregularity in the baseline model components (e.g., stiffness, mass and geometrical parameters). To differentiate the contribution of different components of OoC on the total OAE response, the baseline parameters of the model has been adjusted to vary vibration magnitudes of those components. The preliminary results show that the impedance irregularities generate the phase decay of the stimulus-frequency OAEs more than the nonlinear distortion (e.g., 1-2 cycles per 1kHz with 10% random perturbations of Young’s modulus of the basilar membrane), consistent with data in the literature. The perturbations of other model parameters are under investigation.

Using Cochlear Microphonic Potentials to Localize Peripheral Hearing Loss.

The cochlear microphonic (CM) is created primarily by the receptor currents of outer hair cells (OHCs) and may therefore be useful for identifying cochlear regions with impaired OHCs. However, the CM measured across the frequency range with round-window or ear-canal electrodes lacks place-specificity as it is dominated by cellular sources located most proximal to the recording site (e.g., at the cochlear base). To overcome this limitation, we extract the “residual” CM (rCM), defined as the complex difference between the CM measured with and without an additional tone (saturating tone, ST). If the ST saturates receptor currents near the peak of its excitation pattern, then the rCM should reflect the activity of OHCs in that region. To test this idea, we measured round-window CMs in chinchillas in response to low-level probe tones presented alone or with an ST ranging from 1 to 2.6 times the probe frequency. CMs were measured both before and after inducing a local impairment in cochlear function (a 4-kHz notch-type acoustic trauma). Following the acoustic trauma, little change was observed in the probe-alone CM. In contrast, rCMs were reduced in a frequency-specific manner. When shifts in rCM levels were plotted vs. the ST frequency, they matched well the frequency range of shifts in neural thresholds. These results suggest that rCMs originate near the cochlear place tuned to the ST frequency and thus can be used to assess OHC function in that region. Our interpretation of the data is supported by predictions of a simple phenomenological model of CM generation and two-tone interactions. The model indicates that the sensitivity of rCM to acoustic trauma is governed by changes in cochlear response at the ST tonotopic place rather than at the probe place. The model also suggests that a combination of CM and rCM measurements could be used to assess both the site and etiology of sensory hearing loss in clinical applications.

Effect of Successive Administration of Vancomycin and Amikacin on Auditory Function of Immature Animals.

Effect of successive administration vancomycin and amikacin in therapeutic doses on immature auditory organ was compared to single administration of the same drugs in chronic experiments on immature rabbits by recording of short-latency auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE). Drug administration always increased significantly the ABR peak I threshold. Ototoxic antibiotics did not change DPOAE, but selectively affected activity of outer hair cells. No enhancement of the ototoxic effects was observed after successive administration of the two antibiotics.

Conditional deletion of pejvakin in adult outer hair cells causes progressive hearing loss in mice

Mutations in the Pejvakin (Pjvk) gene cause autosomal recessive hearing loss DFNB59 with audiological features of auditory neuropathy spectrum disorder (ANSD) or cochlear dysfunction. The precise mechanisms underlying the variable clinical phenotypes of DFNB59 remain unclear. Here, we demonstrate that mice with conditional ablation of the Pjvk gene in all sensory hair cells or only in outer hair cells (OHCs) show similar auditory phenotypes with early-onset profound hearing loss. By contrast, loss of Pjvk in adult OHCs causes a slowly progressive hearing loss associated with OHC degeneration and delayed loss of inner hair cells (IHCs), indicating a primary role for pejvakin in regulating OHC function and survival. Consistent with this model, synaptic transmission at the IHC ribbon synapse is largely unaffected in sirtaki mice that carry a C-terminal deletion mutation in Pjvk. Using the C-terminal domain of pejvakin as bait, we identified in a cochlear cDNA library ROCK2, an effector for the small GTPase Rho, and the scaffold protein IQGAP1, involved in modulating actin dynamics. Both ROCK2 and IQGAP1 associate via their coiled-coil domains with pejvakin. We conclude that pejvakin is required to sustain OHC activity and survival in a cell-autonomous manner likely involving regulation of Rho signaling.

外有毛細胞の伸縮運動を考慮したヒト蝸牛有限要素モデル

外有毛細胞の伸縮運動を考慮したヒト蝸牛有限要素モデル