Cochlear outer hair cell electromotility enhances organ of Corti motion on a cycle-by-cycle basis at high frequencies in vivo.

Mammalian hearing depends on an amplification process involving prestin, a voltage-sensitive motor protein that enables cochlear outer hair cells (OHCs) to change length and generate force. However, it has been questioned whether this prestin-based somatic electromotility can operate fast enough in vivo to amplify cochlear vibrations at the high frequencies that mammals hear. In this study, we measured sound-evoked vibrations from within the living mouse cochlea and found that the top and bottom of the OHCs move in opposite directions at frequencies exceeding 20 kHz, consistent with fast somatic length changes. These motions are physiologically vulnerable, depend on prestin, and dominate the cochlea's vibratory response to high-frequency sound. This dominance was observed despite mechanisms that clearly low-pass filter the in vivo electromotile response. Low-pass filtering therefore does not critically limit the OHC's ability to move the organ of Corti on a cycle-by-cycle basis. Our data argue that electromotility serves as the primary high-frequency amplifying mechanism within the mammalian cochlea.

A canonical oscillator model of cochlear dynamics.

Nonlinear responses to acoustic signals arise through active processes in the cochlea, which has an exquisite sensitivity and wide dynamic range that can be explained by critical nonlinear oscillations of outer hair cells. Here we ask how the interaction of critical nonlinearities with the basilar membrane and other organ of Corti components could determine tuning properties of the mammalian cochlea. We propose a canonical oscillator model that captures the dynamics of the interaction between the basilar membrane and organ of Corti, using a pair of coupled oscillators for each place along the cochlea. We analyze two models in which a linear oscillator, representing basilar membrane dynamics, is coupled to a nonlinear oscillator poised at a Hopf instability. The coupling in the first model is unidirectional, and that of the second is bidirectional. Parameters are determined by fitting 496 auditory-nerve (AN) tuning curves of macaque monkeys. We find that the unidirectionally and bidirectionally coupled models account equally well for threshold tuning. In addition, however, the bidirectionally coupled model exhibits low-amplitude, spontaneous oscillation in the absence of stimulation, predicting that phase locking will occur before a significant increase in firing frequency, in accordance with well known empirical observations. This leads us to a canonical oscillator cochlear model based on the fundamental principles of critical nonlinear oscillation and coupling dynamics. The model is more biologically realistic than widely used linear or nonlinear filter-based models, yet parsimoniously displays key features of nonlinear mechanistic models. It is efficient enough for computational studies of auditory perception and auditory physiology.

Gata3 is required for the functional maturation of inner hair cells and their innervation in the mouse cochlea.

KEY POINTS: The physiological maturation of auditory hair cells and their innervation requires precise temporal and spatial control of cell differentiation. The transcription factor gata3 is essential for the earliest stages of auditory system development and for survival and synaptogenesis in auditory sensory afferent neurons. We show that during postnatal development in the mouse inner ear gata3 is required for the biophysical maturation, growth and innervation of inner hair cells; in contrast, it is required only for the survival of outer hair cells. Loss of gata3 in inner hair cells causes progressive hearing loss and accounts for at least some of the deafness associated with the human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome. The results show that gata3 is critical for later stages of mammalian auditory system development where it plays distinct, complementary roles in the coordinated maturation of sensory hair cells and their innervation. ABSTRACT: The zinc finger transcription factor gata3 regulates inner ear development from the formation of the embryonic otic placode. Throughout development, gata3 is expressed dynamically in all the major cochlear cell types. Its role in afferent formation is well established but its possible involvement in hair cell maturation remains unknown. Here, we find that in heterozygous gata3 null mice (gata3+/- ) outer hair cells (OHCs) differentiate normally but their numbers are significantly lower. In contrast, inner hair cells (IHCs) survive normally but they fail to acquire adult basolateral membrane currents, retain pre-hearing current and efferent innervation profiles and have fewer ribbon synapses. Targeted deletion of gata3 driven by otoferlin-cre recombinase (gata3fl/fl otof-cre+/- ) in IHCs does not affect OHCs or the number of IHC afferent synapses but it leads to a failure in IHC maturation comparable to that observed in gata3+/- mice. Auditory brainstem responses in gata3fl/fl otof-cre+/- mice reveal progressive hearing loss that becomes profound by 6-7 months, whilst distortion product otoacoustic emissions are no different to control animals up to this age. Our results, alongside existing data, indicate that gata3 has specific, complementary functions in different cell types during inner ear development and that its continued expression in the sensory epithelium orchestrates critical aspects of physiological development and neural connectivity. Furthermore, our work indicates that hearing loss in human hypoparathyroidism, deafness and renal anomaly (HDR) syndrome arises from functional deficits in IHCs as well as loss of function from OHCs and both afferent and efferent neurons.

Nonlinearity and amplification in cochlear responses to single and multi-tone stimuli.

Mechanical displacements of the basilar membrane (BM) and the electrophysiological responses of the auditory outer hair cells (OHCs) are key components of the frequency tuning and cochlear amplification in the mammalian cochlea. In the work presented here, we measured the responses of (1) the extracellular voltage generated by OHCs (VOHC) and (2) displacements within the organ of Corti complex (OCC) to a multi-tone stimulus, and to single tones. Using optical coherence tomography (OCT), we were able to measure displacements of different layers in the OCC simultaneously, in the base of the gerbil cochlea. We explored the effect of the two types of sound stimuli to the nonlinear behavior of voltage and displacement in two frequency regions: a frequency region below the BM nonlinearity (sub-BF region: f < ∼0.7 BF), and in the best frequency (BF) region. In the sub-BF region, BM motion (XBM) had linear growth for both stimulus types, and the motion in the OHC region (XOHC) was mildly nonlinear for single tones, and relatively strongly nonlinear for multi-tones. Sub-BF, the nonlinear character of VOHC was similar to that of XOHC. In the BF region XBM, VOHC and XOHC all possessed the now-classic nonlinearity of the BF peak. Coupling these observations with previous findings on phasing between OHC force and traveling wave motions, we propose the following framework for cochlear nonlinearity: The BF-region nonlinearity is an amplifying nonlinearity, in which OHC forces input power into the traveling wave, allowing it to travel further apical to the region where it peaks. The sub-BF nonlinearity is a non-amplifying nonlinearity; it represents OHC electromotility, and saturates due to OHC current saturation, but the OHC forces do not possess the proper phasing to feed power into the traveling wave.

Coordinated calcium signalling in cochlear sensory and non-sensory cells refines afferent innervation of outer hair cells.

Outer hair cells (OHCs) are highly specialized sensory cells conferring the fine-tuning and high sensitivity of the mammalian cochlea to acoustic stimuli. Here, by genetically manipulating spontaneous Ca2+ signalling in mice in vivo, through a period of early postnatal development, we find that the refinement of OHC afferent innervation is regulated by complementary spontaneous Ca2+ signals originating in OHCs and non-sensory cells. OHCs fire spontaneous Ca2+ action potentials during a narrow period of neonatal development. Simultaneously, waves of Ca2+ activity in the non-sensory cells of the greater epithelial ridge cause, via ATP-induced activation of P2X3 receptors, the increase and synchronization of the Ca2+ activity in nearby OHCs. This synchronization is required for the refinement of their immature afferent innervation. In the absence of connexin channels, Ca2+ waves are impaired, leading to a reduction in the number of ribbon synapses and afferent fibres on OHCs. We propose that the correct maturation of the afferent connectivity of OHCs requires experience-independent Ca2+ signals from sensory and non-sensory cells.

Amplification and Suppression of Traveling Waves along the Mouse Organ of Corti: Evidence for Spatial Variation in the Longitudinal Coupling of Outer Hair Cell-Generated Forces.

Mammalian hearing sensitivity and frequency selectivity depend on a mechanical amplification process mediated by outer hair cells (OHCs). OHCs are situated within the organ of Corti atop the basilar membrane (BM), which supports sound-evoked traveling waves. It is well established that OHCs generate force to selectively amplify BM traveling waves where they peak, and that amplification accumulates from one location to the next over this narrow cochlear region. However, recent measurements demonstrate that traveling waves along the apical surface of the organ of Corti, the reticular lamina (RL), are amplified over a much broader region. Whether OHC forces accumulate along the length of the RL traveling wave to provide a form of "global" cochlear amplification is unclear. Here we examined the spatial accumulation of RL amplification. In mice of either sex, we used tones to suppress amplification from different cochlear regions and examined the effect on RL vibrations near and far from the traveling-wave peak. We found that although OHC forces amplify the entire RL traveling wave, amplification only accumulates near the peak, over the same region where BM motion is amplified. This contradicts the notion that RL motion is involved in a global amplification mechanism and reveals that the mechanical properties of the BM and organ of Corti tune how OHC forces accumulate spatially. Restricting the spatial buildup of amplification enhances frequency selectivity by sharpening the peaks of cochlear traveling waves and constrains the number of OHCs responsible for mechanical sensitivity at each location.SIGNIFICANCE STATEMENT Outer hair cells generate force to amplify traveling waves within the mammalian cochlea. This force generation is critical to the ability to detect and discriminate sounds. Nevertheless, how these forces couple to the motions of the surrounding structures and integrate along the cochlear length remains poorly understood. Here we demonstrate that outer hair cell-generated forces amplify traveling-wave motion on the organ of Corti throughout the wave's extent, but that these forces only accumulate longitudinally over a region near the wave's peak. The longitudinal coupling of outer hair cell-generated forces is therefore spatially tuned, likely by the mechanical properties of the basilar membrane and organ of Corti. Our findings provide new insight into the mechanical processes that underlie sensitive hearing.

High frequency transient-evoked otoacoustic emission measurements using chirp and click stimuli.

Transient-evoked otoacoustic emissions (TEOAEs) at high frequencies are a non-invasive physiological test of basilar membrane mechanics at the basal end, and have clinical potential to detect risk of hearing loss related to outer-hair-cell dysfunction. Using stimuli with constant incident pressure across frequency, TEOAEs were measured in experiment 1 at low frequencies (0.7-8 kHz) and high frequencies (7.1-14.7 kHz) in adults with normal hearing up to 8 kHz and varying hearing levels from 9 to 16 kHz. In combination with click stimuli, chirp stimuli were used with slow, medium and fast sweep rates for which the local frequency increased or decreased with time. Chirp TEOAEs were transformed into equivalent click TEOAEs by inverse filtering out chirp stimulus phase, and analyzed similarly to click TEOAEs. To improve detection above 8 kHz, TEOAEs were measured in experiment 2 with higher-level stimuli and longer averaging times. These changes increased the TEOAE signal-to-noise ratio (SNR) by 10 dB. Slower sweep rates were investigated but the elicited TEOAEs were detected in fewer ears compared to faster rates. Data were acquired in adults and children (age 11-17 y), including children with cystic fibrosis (CF) treated with ototoxic antibiotics. Test-retest measurements revealed satisfactory repeatability of high-frequency TEOAE SNR (median of 1.3 dB) and coherence synchrony measure, despite small test-retest differences related to changes in forward and reverse transmission in the ear canal. The results suggest the potential use of such tests to screen for sensorineural hearing loss, including ototoxic loss. Experiment 2 was a feasibility study to explore TEOAE test parameters that might be used in a full-scale study to screen CF patients for risk of ototoxic hearing loss.

Effect of Blood Group on Ultrahigh Frequency Auditory Sensitivity

Abstract Introduction Individuals with blood group O are reported to have reduced otoacoustic emissions (OAEs) compared with individuals with different blood groups. Objective The present study attempted to determine if the blood group has any effect on high-frequency auditory sensitivity using ultrahigh-frequency audiometry and ultrahigh-frequency distortion product otoacoustic emissions (DPOAEs). Methods High-frequency thresholds and high-frequency DPOAEs were measured in 60 individuals with normal hearing and different blood groups. Results The results of the study showed that there was a significant reduction in DPOAE amplitude for individuals with blood group O compared with individuals with other blood groups. However, there was no significant difference in ultrahigh-frequency thresholds across the blood groups. Conclusion This reduction in OAE amplitude may be attributed to a lower number of healthy outer hair cells in individuals with blood group O. Further studies on larger groups of individuals are essential for a better generalization of the results.

Spontaneous Otoacoustic Emissions in TectaY1870C/+ Mice Reflect Changes in Cochlear Amplification and How It Is Controlled by the Tectorial Membrane.

Spontaneous otoacoustic emissions (SOAEs) recorded from the ear canal in the absence of sound reflect cochlear amplification, an outer hair cell (OHC) process required for the extraordinary sensitivity and frequency selectivity of mammalian hearing. Although wild-type mice rarely emit, those with mutations that influence the tectorial membrane (TM) show an incidence of SOAEs similar to that in humans. In this report, we characterized mice with a missense mutation in Tecta, a gene required for the formation of the striated-sheet matrix within the core of the TM. Mice heterozygous for the Y1870C mutation (TectaY1870C/+ ) are prolific emitters, despite a moderate hearing loss. Additionally, Kimura's membrane, into which the OHC stereocilia insert, separates from the main body of the TM, except at apical cochlear locations. Multimodal SOAEs are also observed in TectaY1870C/+ mice where energy is present at frequencies that are integer multiples of a lower-frequency SOAE (the primary). Second-harmonic SOAEs, at twice the frequency of a lower-frequency primary, are the most frequently observed. These secondary SOAEs are found in spatial regions where stimulus-evoked OAEs are small or in the noise floor. Introduction of high-level suppressors just above the primary SOAE frequency reduce or eliminate both primary and second-harmonic SOAEs. In contrast, second-harmonic SOAEs are not affected by suppressors, either above or below the second-harmonic SOAE frequency, even when they are much larger in amplitude. Hence, second-harmonic SOAEs do not appear to be spatially separated from their primaries, a finding that has implications for cochlear mechanics and the consequences of changes to TM structure.

Modulation of auditory percepts by transcutaneous electrical stimulation.

Transcutaneous, electrical stimulation with electrodes placed on the mastoid processes represents a specific way to elicit vestibular reflexes in humans without active or passive subject movements, for which the term galvanic vestibular stimulation was coined. It has been suggested that galvanic vestibular stimulation mainly affects the vestibular periphery, but whether vestibular hair cells, vestibular afferents, or a combination of both are excited, is still a matter of debate. Galvanic vestibular stimulation has been in use since the late 18th century, but despite the long-known and well-documented effects on the vestibular system, reports of the effect of electrical stimulation on the adjacent cochlea or the ascending auditory pathway are surprisingly sparse. The present study examines the effect of transcutaneous, electrical stimulation of the human auditory periphery employing evoked and spontaneous otoacoustic emissions and several psychoacoustic measures. In particular, level growth functions of distortion product otoacoustic emissions were recorded during electrical stimulation with alternating currents (2 Hz, 1-4 mA in 1 mA-steps). In addition, the level and frequency of spontaneous otoacoustic emissions were followed before, during, and after electrical stimulation (2 Hz, 1-4 mA). To explore the effect of electrical stimulation on the retrocochlear level (i.e. on the ascending auditory pathway beyond the cochlea), psychoacoustic experiments were carried out. Specifically, participants indicated whether electrical stimulation (4 Hz, 2 and 3 mA) induced amplitude modulations of the perception of a pure tone, and of auditory illusions after presentation of either an intense, low-frequency sound (Bounce tinnitus) or a faint band-stop noise (Zwicker tone). These three psychoacoustic measures revealed significant perceived amplitude modulations during electrical stimulation in the majority of participants. However, no significant changes of evoked and spontaneous otoacoustic emissions could be detected during electrical stimulation relative to recordings without electrical stimulation. The present findings show that cochlear function, as assessed with spontaneous and evoked otoacoustic emissions, is not affected by transcutaneous electrical stimulation, at the currents used in this study. Psychoacoustic measures like pure tone perception, but also auditory illusions, are affected by electrical stimulation. This indicates that activity of the retrocochlear ascending auditory pathway is modulated during transcutaneous electrical stimulation.

Hair cell force generation does not amplify or tune vibrations within the chicken basilar papilla.

Frequency tuning within the auditory papilla of most non-mammalian species is electrical, deriving from ion-channel resonance within their sensory hair cells. In contrast, tuning within the mammalian cochlea is mechanical, stemming from active mechanisms within outer hair cells that amplify the basilar membrane travelling wave. Interestingly, hair cells in the avian basilar papilla demonstrate both electrical resonance and force-generation, making it unclear which mechanism creates sharp frequency tuning. Here, we measured sound-induced vibrations within the apical half of the chicken basilar papilla in vivo and found broadly-tuned travelling waves that were not amplified. However, distortion products were found in live but not dead chickens. These findings support the idea that avian hair cells do produce force, but that their effects on vibration are small and do not sharpen tuning. Therefore, frequency tuning within the apical avian basilar papilla is not mechanical, and likely derives from hair cell electrical resonance.

Quercetin protects against hair cell loss in the zebrafish lateral line and guinea pig cochlea.

Eighteen supplement drugs were screened using hair cells to determine a protective effect against the adverse effects of neomycin by using the zebrafish lateral line. The zebrafish were administered the supplement drugs 1 h before neomycin exposure. One hour later, animals were fixed in paraformaldehyde. Dose-response curves were generated to evaluate the protective effect on hair cells. The screen identified 3 supplements (quercetin, catechin and tannic acid). Three minutes after exposure to neomycin, increased antioxidant activity was found in the lateral line hair cells, as determined by the analysis of oxidative stress. Quercetin decreases antioxidant activity. The identified drugs were also investigated to determine whether they protect the cochlea against noise-induced hearing loss in guinea pigs. The drugs were administered via the intraperitoneal route in the guinea pigs 3 days before and 4 days after noise exposure. Seven days after noise exposure (130-dB sound pressure level for 3 h), the auditory brainstem response threshold shifts were assessed. We observed that the auditory brainstem response threshold shift was significantly less in the quercetin group than in the vehicle control group. The results of our study indicate that screening drugs using zebrafish can determine additional protective drugs for the inner ear.

The potential use of low-frequency tones to locate regions of outer hair cell loss.

Current methods used to diagnose cochlear hearing loss are limited in their ability to determine the location and extent of anatomical damage to various cochlear structures. In previous experiments, we have used the electrical potential recorded at the round window -the cochlear response (CR) -to predict the location of damage to outer hair cells in the gerbil. In a follow-up experiment, we applied 10 mM ouabain to the round window niche to reduce neural activity in order to quantify the neural contribution to the CR. We concluded that a significant proportion of the CR to a 762 Hz tone originated from phase-locking activity of basal auditory nerve fibers, which could have contaminated our conclusions regarding outer hair cell health. However, at such high concentrations, ouabain may have also affected the responses from outer hair cells, exaggerating the effect we attributed to the auditory nerve. In this study, we lowered the concentration of ouabain to 1 mM and determined the physiologic effects on outer hair cells using distortion-product otoacoustic emissions. As well as quantifying the effects of 1 mM ouabain on the auditory nerve and outer hair cells, we attempted to reduce the neural contribution to the CR by using near-infrasonic stimulus frequencies of 45 and 85 Hz, and hypothesized that these low-frequency stimuli would generate a cumulative amplitude function (CAF) that could reflect damage to hair cells in the apex more accurately than the 762 stimuli. One hour after application of 1 mM ouabain, CR amplitudes significantly increased, but remained unchanged in the presence of high-pass filtered noise conditions, suggesting that basal auditory nerve fibers have a limited contribution to the CR at such low frequencies.

Minimal basilar membrane motion in low-frequency hearing.

Low-frequency hearing is critically important for speech and music perception, but no mechanical measurements have previously been available from inner ears with intact low-frequency parts. These regions of the cochlea may function in ways different from the extensively studied high-frequency regions, where the sensory outer hair cells produce force that greatly increases the sound-evoked vibrations of the basilar membrane. We used laser interferometry in vitro and optical coherence tomography in vivo to study the low-frequency part of the guinea pig cochlea, and found that sound stimulation caused motion of a minimal portion of the basilar membrane. Outside the region of peak movement, an exponential decline in motion amplitude occurred across the basilar membrane. The moving region had different dependence on stimulus frequency than the vibrations measured near the mechanosensitive stereocilia. This behavior differs substantially from the behavior found in the extensively studied high-frequency regions of the cochlea.

The acquisition of mechano-electrical transducer current adaptation in auditory hair cells requires myosin VI.

KEY POINTS: The transduction of sound into electrical signals occurs at the hair bundles atop sensory hair cells in the cochlea, by means of mechanosensitive ion channels, the mechano-electrical transducer (MET) channels. The MET currents decline during steady stimuli; this is termed adaptation and ensures they always work within the most sensitive part of their operating range, responding best to rapidly changing (sound) stimuli. In this study we used a mouse model (Snell's waltzer) for hereditary deafness in humans that has a mutation in the gene encoding an unconventional myosin, myosin VI, which is present in the hair bundles. We found that in the absence of myosin VI the MET current fails to acquire its characteristic adaptation as the hair bundles develop. We propose that myosin VI supports the acquisition of adaptation by removing key molecules from the hair bundle that serve a temporary, developmental role. ABSTRACT: Mutations in Myo6, the gene encoding the (F-actin) minus end-directed unconventional myosin, myosin VI, cause hereditary deafness in mice (Snell's waltzer) and humans. In the sensory hair cells of the cochlea, myosin VI is expressed in the cell bodies and along the stereocilia that project from the cells' apical surface. It is required for maintaining the structural integrity of the mechanosensitive hair bundles formed by the stereocilia. In this study we investigate whether myosin VI contributes to mechano-electrical transduction. We report that Ca(2+) -dependent adaptation of the mechano-electrical transducer (MET) current, which serves to keep the transduction apparatus operating within its most sensitive range, is absent in outer and inner hair cells from homozygous Snell's waltzer mutant mice, which fail to express myosin VI. The operating range of the MET channels is also abnormal in the mutants, resulting in the absence of a resting MET current. We found that cadherin 23, a component of the hair bundle's transient lateral links, fails to be downregulated along the length of the stereocilia in maturing Myo6 mutant mice. MET currents of heterozygous littermates appear normal. We propose that myosin VI, by removing key molecules from developing hair bundles, is required for the development of the MET apparatus and its Ca(2+) -dependent adaptation.

Selective Inner Hair Cell Dysfunction in Chinchillas Impairs Hearing-in-Noise in the Absence of Outer Hair Cell Loss.

Poorer hearing in the presence of background noise is a significant problem for the hearing impaired. Ototoxic drugs, ageing, and noise exposure can damage the sensory hair cells of the inner ear that are essential for normal hearing sensitivity. The relationship between outer hair cell (OHC) loss and progressively poorer hearing sensitivity in quiet or in competing background noise is supported by a number of human and animal studies. In contrast, the effect of moderate inner hair cell (IHC) loss or dysfunction shows almost no impact on behavioral measures of hearing sensitivity in quiet, when OHCs remain intact, but the relationship between selective IHC loss and hearing in noise remains relatively unknown. Here, a moderately high dose of carboplatin (75 mg/kg) that produced IHC loss in chinchillas ranging from 40 to 80 % had little effect on thresholds in quiet. However, when tested in the presence of competing broadband (BBN) or narrowband noise (NBN), thresholds increased significantly. IHC loss >60 % increased signal-to-noise ratios (SNRs) for tones (500-11,300 Hz) in competing BBN by 5-10 dB and broadened the masking function under NBN. These data suggest that IHC loss or dysfunction may play a significant role in listening in noise independent of OHC integrity and that these deficits may be present even when thresholds in quiet are within normal limits.

Prestin-Dependence of Outer Hair Cell Survival and Partial Rescue of Outer Hair Cell Loss in PrestinV499G/Y501H Knockin Mice.

A knockin (KI) mouse expressing mutated prestinV499G/Y501H (499 prestin) was created to study cochlear amplification. Recordings from isolated outer hair cells (OHC) in this mutant showed vastly reduced electromotility and, as a consequence, reduced hearing sensitivity. Although 499 prestin OHCs were normal in stiffness and longer than OHCs lacking prestin, accelerated OHC death was unexpectedly observed relative to that documented in prestin knockout (KO) mice. These observations imply an additional role of prestin in OHC maintenance besides its known requirement for mammalian cochlear amplification. In order to gain mechanistic insights into prestin-associated OHC loss, we implemented several interventions to improve survival. First, 499 prestin KI's were backcrossed to Bak KO mice, which lack the mitochondrial pro-apoptotic gene Bak. Because oxidative stress is implicated in OHC death, another group of 499 prestin KI mice was fed the antioxidant diet, Protandim. 499 KI mice were also backcrossed onto the FVB murine strain, which retains excellent high-frequency hearing well into adulthood, to reduce the compounding effect of age-related hearing loss associated with the original 499 prestin KIs. Finally, a compound heterozygous (chet) mouse expressing one copy of 499 prestin and one copy of KO prestin was also created to reduce quantities of 499 prestin protein. Results show reduction in OHC death in chets, and in 499 prestin KIs on the FVB background, but only a slight improvement in OHC survival for mice receiving Protandim. We also report that improved OHC survival in 499 prestin KIs had little effect on hearing phenotype, reaffirming the original contention about the essential role of prestin's motor function in cochlear amplification.

Cochlear Function Monitoring after Spinal Anesthesia.

BACKGROUND: The aim of the study was to examine the effect of spinal anesthesia on the function of cochlear outer hair cells (OHCs), determined by means of objective distortion product otoacoustic emissions (DPOAE) testing. To the best of our knowledge, our study was the second OAE-based analysis of cochlear function during spinal anesthesia, and the only experiment including such a large group of patients. MATERIAL AND METHODS: The study included 20 patients (18 men and 2 women) subjected to a scheduled uretherorenoscopic lithotripsy with routine spinal anesthesia with 10 mg (2 ml) of 0.5% hyperbaric bupivacaine and 50 µg (1 ml) of fentanyl. The levels of DPOAEs and background noise at 1000-6000 Hz were recorded prior to and immediately after the anesthesia, and on the postoperative day 2. RESULTS: We did not find significant differences between DPOAEs values recorded prior to and immediately after the anesthesia. The only exception pertained to 5652 Hz, at which a significantly higher level of DPOAEs was observed immediately after the anesthesia. The levels of DPOAEs at 2002 Hz and 2380 Hz collected on the postoperative day 2 were significantly higher than the respective baseline values. Irrespective of the frequency and time of testing, we did not find any significant differences between the recorded levels of background noise. CONCLUSIONS: Our findings point to the lack of a detrimental effect of spinal anesthesia on objectively evaluated cochlear function, and thus suggest that this method is safe, even for OHCs, which are extremely susceptible to exogenous and endogenous injuries.

The development of a fast method for recording Schroeder-phase masking functions.

Schroeder-phase masking complexes have been used in many psychophysical experiments to examine the phase curvature of cochlear filtering at characteristic frequencies, and other aspects of cochlear nonlinearity. In a normal nonlinear cochlea, changing the "scalar factor" of the Schroeder-phase masker from -1 through 0 to +1 results in a marked difference in the measured masked thresholds, whereas this difference is reduced in ears with damaged outer hair cells. Despite the valuable information it may give, one disadvantage of the Schroeder-phase masking procedure is the length of the test - using the conventional three-alternative forced-choice technique to measure a masking function takes around 45 min for one combination of probe frequency and intensity. As an alternative, we have developed a fast method of recording these functions which uses a Békésy tracking procedure. Testing at 500 Hz in normal hearing participants, we demonstrate that our fast method: i) shows good agreement with the conventional method; ii) shows high test-retest reliability; and iii) shortens the testing time to 8 min.

[Auditory fatigue]. / Fatiga auditiva.

INTRODUCTION AND OBJECTIVES: Given the relevance of possible hearing losses due to sound overloads and the short list of references of objective procedures for their study, we provide a technique that gives precise data about the audiometric profile and recruitment factor. Our objectives were to determine peripheral fatigue, through the cochlear microphonic response to sound pressure overload stimuli, as well as to measure recovery time, establishing parameters for differentiation with regard to current psychoacoustic and clinical studies. MATERIAL AND METHOD: We used specific instruments for the study of cochlear microphonic response, plus a function generator that provided us with stimuli of different intensities and harmonic components. In Wistar rats, we first measured the normal microphonic response and then the effect of auditory fatigue on it. RESULTS: Using a 60dB pure tone acoustic stimulation, we obtained a microphonic response at 20dB. We then caused fatigue with 100dB of the same frequency, reaching a loss of approximately 11dB after 15minutes; after that, the deterioration slowed and did not exceed 15dB. By means of complex random tone maskers or white noise, no fatigue was caused to the sensory receptors, not even at levels of 100dB and over an hour of overstimulation. CONCLUSIONS: No fatigue was observed in terms of sensory receptors. Deterioration of peripheral perception through intense overstimulation may be due to biochemical changes of desensitisation due to exhaustion. Auditory fatigue in subjective clinical trials presumably affects supracochlear sections. The auditory fatigue tests found are not in line with those obtained subjectively in clinical and psychoacoustic trials.