Medial Olivocochlear Efferents Research Articles

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.

Alpha9alpha10 knockout mice show altered physiological and behavioral responses to signals in masking noise.

Medial olivocochlear (MOC) efferents modulate outer hair cell motility through specialized nicotinic acetylcholine receptors to support encoding of signals in noise. Transgenic mice lacking the alpha9 subunits of these receptors (α9KOs) have normal hearing in quiet and noise, but lack classic cochlear suppression effects and show abnormal temporal, spectral, and spatial processing. Mice deficient for both the alpha9 and alpha10 receptor subunits (α9α10KOs) may exhibit more severe MOC-related phenotypes. Like α9KOs, α9α10KOs have normal auditory brainstem response (ABR) thresholds and weak MOC reflexes. Here, we further characterized auditory function in α9α10KO mice. Wild-type (WT) and α9α10KO mice had similar ABR thresholds and acoustic startle response amplitudes in quiet and noise, and similar frequency and intensity difference sensitivity. α9α10KO mice had larger ABR Wave I amplitudes than WTs in quiet and noise. Other ABR metrics of hearing-in-noise function yielded conflicting findings regarding α9α10KO susceptibility to masking effects. α9α10KO mice also had larger startle amplitudes in tone backgrounds than WTs. Overall, α9α10KO mice had grossly normal auditory function in quiet and noise, although their larger ABR amplitudes and hyperreactive startles suggest some auditory processing abnormalities. These findings contribute to the growing literature showing mixed effects of MOC dysfunction on hearing.

Exploring the origins of decreased sound tolerance in tinnitus patients.

This study aimed to confirm the characteristics of auditory function alterations in tinnitus patients with concomitant decreased sound tolerance (ST) and provide insights for developing tailored therapeutic approaches. A retrospective analysis was conducted on patient records from a tertiary university hospital's tinnitus clinic between March 2020 and June 2023. Demographic attributes and audiological profiles were reviewed. Patients were categorized into Group 1 if loudness discomfort level test outcomes were 77 dB or below, measured using an average of frequencies from 250 Hz to 8 kHz. The remaining patients were allocated to Group 2. Among the 434 tinnitus patients, 115 (26.5%) demonstrated decreased ST and were classified as Group 1. This group exhibited higher DPOAE amplitudes (p < 0.001), shortened latency, and decreased threshold of ABR wave V bilaterally (p < 0.05). No significant disparities were observed in gender, age, tinnitus handicap inventory, visual analog scale, and pure-tone audiometry results except subjective hyperacusis. Binary logistic regression analysis utilizing the forward conditional method revealed that the difference between groups was independently linked to DPOAE response at 7,277 Hz on the left side [B = 0.093, p < 0.001, EXP(B) = 1.07, 95% CI = 1.044-1.153]. Increased DPOAE amplitude and shorter and decreased ABR wave V in tinnitus patients with decreased ST might suggest a possible association with lesions in or around the superior olivary complex or higher central auditory pathway, potentially linked to the inhibition of medial olivocochlear efferents.

Enhanced suppression of otoacoustic emissions by contralateral stimulation in Parkinson's disease.

Dopamine depletion affects several aspects of hearing function. Previous work [Wu, Yi, Manca, Javaid, Lauer, and Glowatzki, eLife 9, e52419 (2020)] demonstrated the role of dopamine in reducing the firing rates of inner ear cells, which is thought to decrease synaptic excitotoxicity. Thus, a lack of dopamine could indirectly increase acoustic stimulation of medial olivocochlear efferents. To investigate that, here we studied contralateral suppression of distortion product otoacoustic emissions in a population of Parkinsonian patients, compared to an age-matched control group, both audiometrically tested. To rule out activation of the acoustic reflex, middle ear impedance was monitored during testing. The results show significantly stronger contralateral suppression in the patient group.

Auditory Deprivation during Development Alters Efferent Neural Feedback and Perception.

Auditory experience plays a critical role in hearing development. Developmental auditory deprivation because of otitis media, a common childhood disease, produces long-standing changes in the central auditory system, even after the middle ear pathology is resolved. The effects of sound deprivation because of otitis media have been mostly studied in the ascending auditory system but remain to be examined in the descending pathway that runs from the auditory cortex to the cochlea via the brainstem. Alterations in the efferent neural system could be important because the descending olivocochlear pathway influences the neural representation of transient sounds in noise in the afferent auditory system and is thought to be involved in auditory learning. Here, we show that the inhibitory strength of the medial olivocochlear efferents is weaker in children with a documented history of otitis media relative to controls; both boys and girls were included in the study. In addition, children with otitis media history required a higher signal-to-noise ratio on a sentence-in-noise recognition task than controls to achieve the same criterion performance level. Poorer speech-in-noise recognition, a hallmark of impaired central auditory processing, was related to efferent inhibition, and could not be attributed to the middle ear or cochlear mechanics.SIGNIFICANCE STATEMENT Otitis media is the second most common reason children go to the doctor. Previously, degraded auditory experience because of otitis media has been associated with reorganized ascending neural pathways, even after middle ear pathology resolved. Here, we show that altered afferent auditory input because of otitis media during childhood is also associated with long-lasting reduced descending neural pathway function and poorer speech-in-noise recognition. These novel, efferent findings may be important for the detection and treatment of childhood otitis media.

Contralateral inhibition of distortion product otoacoustic emissions in young noise-exposed Veterans.

Although animal models show a clear link between noise exposure and damage to afferent cochlear synapses, the relationship between noise exposure and efferent function appears to be more complex. Animal studies indicate that high intensity noise exposure reduces efferent medial olivocochlear (MOC) reflex strength, whereas chronic moderate noise exposure is associated with a conditioning effect that enhances the MOC reflex. The MOC reflex is predicted to improve speech-in-noise perception and protects against noise-induced auditory damage by reducing cochlear gain. In humans, MOC reflex strength can be estimated by measuring contralateral inhibition of distortion product otoacoustic emissions (DPOAEs). The objective of this study was to determine the impact of military noise exposure on efferent auditory function by measuring DPOAE contralateral inhibition in young Veterans and non-Veterans with normal audiograms. Compared with non-Veteran controls, Veterans with high levels of reported noise exposure demonstrated a trend of reduced contralateral inhibition across a broad frequency range, suggesting efferent damage. Veterans with moderate noise exposure showed trends of reduced inhibition from 3 to 4 kHz but greater inhibition from 1 to 1.5 kHz, consistent with conditioning. These findings suggest that, in humans, the impact of noise exposure on the MOC reflex differs depending on the noise intensity and duration.

The Cholinergic Lateral Line Efferent Synapse: Structural, Functional and Molecular Similarities With Those of the Cochlea.

Vertebrate hair cell (HC) systems are innervated by efferent fibers that modulate their response to external stimuli. In mammals, the best studied efferent-HC synapse, the cholinergic medial olivocochlear (MOC) efferent system, makes direct synaptic contacts with HCs. The net effect of MOC activity is to hyperpolarize HCs through the activation of α9α10 nicotinic cholinergic receptors (nAChRs) and the subsequent activation of Ca2+-dependent SK2 potassium channels. A serious obstacle in research on many mammalian sensory systems in their native context is that their constituent neurons are difficult to access even in newborn animals, hampering circuit observation, mapping, or controlled manipulation. By contrast, fishes and amphibians have a superficial and accessible mechanosensory system, the lateral line (LL), which circumvents many of these problems. LL responsiveness is modulated by efferent neurons which aid to distinguish between external and self-generated stimuli. One component of the LL efferent system is cholinergic and its activation inhibits LL afferent activity, similar to what has been described for MOC efferents. The zebrafish (Danio rerio) has emerged as a powerful model system for studying human hearing and balance disorders, since LL HC are structurally and functionally analogous to cochlear HCs, but are optically and pharmacologically accessible within an intact specimen. Complementing mammalian studies, zebrafish have been used to gain significant insights into many facets of HC biology, including mechanotransduction and synaptic physiology as well as mechanisms of both hereditary and acquired HC dysfunction. With the rise of the zebrafish LL as a model in which to study auditory system function and disease, there has been an increased interest in studying its efferent system and evaluate the similarity between mammalian and piscine efferent synapses. Advances derived from studies in zebrafish include understanding the effect of the LL efferent system on HC and afferent activity, and revealing that an α9-containing nAChR, functionally coupled to SK channels, operates at the LL efferent synapse. In this review, we discuss the tools and findings of these recent investigations into zebrafish efferent-HC synapse, their commonalities with the mammalian counterpart and discuss several emerging areas for future studies.

Investigating Influences of Medial Olivocochlear Efferent System on Central Auditory Processing and Listening in Noise: A Behavioral and Event-Related Potential Study.

This electrophysiological study investigated the role of the medial olivocochlear (MOC) efferents in listening in noise. Both ears of eleven normal-hearing adult participants were tested. The physiological tests consisted of transient-evoked otoacoustic emission (TEOAE) inhibition and the measurement of cortical event-related potentials (ERPs). The mismatch negativity (MMN) and P300 responses were obtained in passive and active listening tasks, respectively. Behavioral responses for the word recognition in noise test were also analyzed. Consistent with previous findings, the TEOAE data showed significant inhibition in the presence of contralateral acoustic stimulation. However, performance in the word recognition in noise test was comparable for the two conditions (i.e., without contralateral stimulation and with contralateral stimulation). Peak latencies and peak amplitudes of MMN and P300 did not show changes with contralateral stimulation. Behavioral performance was also maintained in the P300 task. Together, the results show that the peripheral auditory efferent effects captured via otoacoustic emission (OAE) inhibition might not necessarily be reflected in measures of central cortical processing and behavioral performance. As the MOC effects may not play a role in all listening situations in adults, the functional significance of the cochlear effects of the medial olivocochlear efferents and the optimal conditions conducive to corresponding effects in behavioral and cortical responses remain to be elucidated.

The role of efferents in human auditory development: efferent inhibition predicts frequency discrimination in noise for children.

The descending corticofugal fibers originate from the auditory cortex and exert control on the periphery via the olivocochlear efferents. Medial efferents are thought to enhance the discriminability of transient sounds in background noise. In addition, the observation of deleterious long-term effects of efferent sectioning on the response properties of auditory nerve fibers in neonatal cats supports an efferent-mediated control of normal development. However, the role of the efferent system in human hearing remains unclear. The objective of the present study was to test the hypothesis that the medial efferents are involved in the development of frequency discrimination in noise. The hypothesis was examined with a combined behavioral and physiological approach. Frequency discrimination in noise and efferent inhibition were measured in 5- to 12-yr-old children (n = 127) and young adults (n = 37). Medial efferent strength was noninvasively assayed with a rigorous otoacoustic emission protocol. Results revealed an age-mediated relationship between efferent inhibition and frequency discrimination in noise. Efferent inhibition strongly predicted frequency discrimination in noise for younger children (5-9 yr). However, for older children (>9 yr) and adults, efferent inhibition was not related to frequency discrimination in noise. These findings support the role of efferents in the development of hearing-in-noise in humans; specifically, younger children compared with older children and adults are relatively more dependent on efferent inhibition for extracting relevant cues in noise. Additionally, the present findings caution against postulating an oversimplified relationship between efferent inhibition and measures of auditory perception in humans.NEW & NOTEWORTHY Despite several decades of research, the functional role of medial olivocochlear efferents in humans remains controversial and is thought to be insignificant. Here it is shown that medial efferent inhibition strongly predicts frequency discrimination in noise for younger children but not for older children and adults. Young children are relatively more dependent on the efferent system for listening-in-noise. This study highlights the role of the efferent system in hearing-in-noise during childhood development.

Medial olivocochlear suppression in musicians versus non-musicians.

The medial olivocochlear efferent (MOCE) branch synapses with outer hair cells (OHCs), and the efferent pathway can be activated via a contralateral acoustic stimulus (CAS). The activation of MOCE can change OHC motile responses and convert signals that are capable of controlling the sensitivity of the peripheral hearing system in a frequency-specific manner. The aim of this study was to examine the MOCE system activity in professional musicians using transient evoked otoacoustic emission test and CAS. Musician group showed stronger suppression in all frequency bands in the presence of CAS.

Exploring the Role of Medial Olivocochlear Efferents on the Detection of Amplitude Modulation for Tones Presented in Noise.

The medial olivocochlear reflex has been hypothesized to improve the detection and discrimination of dynamic signals in noisy backgrounds. This hypothesis was tested here by comparing behavioral outcomes with otoacoustic emissions. The effects of a precursor on amplitude-modulation (AM) detection were measured for a 1- and 6-kHz carrier at levels of 40, 60, and 80dB SPL in a two-octave-wide noise masker with a level designed to produce poor, but above-chance, performance. Three types of precursor were used: a two-octave noise band, an inharmonic complex tone, and a pure tone. Precursors had the same overall level as the simultaneous noise masker that immediately followed the precursor. The noise precursor produced a large improvement in AM detection for both carrier frequencies and at all three levels. The complex tone produced a similarly large improvement in AM detection at the highest level but had a smaller effect for the two lower carrier levels. The tonal precursor did not significantly affect AM detection in noise. Comparisons of behavioral thresholds and medial olivocochlear efferent effects on stimulus frequency otoacoustic emissions measured with similar stimuli did not support the hypothesis that efferent-based reduction of cochlear responses contributes to the precursor effects on AM detection.

Modeling the effects of medial olivocochlear efferent stimulation at the level of the inferior colliculus.

Various studies on medial olivocochlear (MOC) efferents have implicated it in multiple roles in the auditory system (e.g., dynamic range adaptation, masking reduction, and selective attention). This study presents a systematic simulation of inferior colliculus (IC) responses with and without electrical stimulation of the MOC. Phenomenological models of the responses of auditory nerve (AN) fibers and IC neurons were used to this end. The simulated responses were highly consistent with physiological data (replicated 3 of the 4 known rate-level responses all MOC effects-shifts, high stimulus level reduction and enhancement). Complex MOC efferent effects which were previously thought to require integration from different characteristic frequency (CF) neurons were simulated using the same frequency inhibition excitation circuitry. MOC-induced enhancing effects were found only in neurons with a CF range from 750Hz to 2kHz. This limited effect is indicative of the role of MOC activation on the AN responses at the stimulus offset.

Implementing an efferent signal into an auditory pathway model for tone-in-noise detection

Simultaneous tone-in-noise detection has been studied extensively, but typically without consideration of the medial olivocochlear (MOC) efferents. We are testing hypotheses for masked detection using a central auditory model with a signal from midbrain to MOC. Masked tones are encoded in the rate profile of band-enhanced (BE) inferior colliculus (IC) neurons, which are excited by a range of modulation frequencies. Peripheral responses to noise are characterized by large fluctuations, an effective stimulus for BE IC neurons. In contrast, peripheral channels tuned near the tone have smaller fluctuations: addition of the tone flattens the signal envelope and also pushes the inner hair cell (IHC) transduction nonlinearity further into saturation. Excitatory projections to MOC from noise-driven BE IC cells would decrease cochlear gain, reducing IHC saturation, and resulting in larger fluctuations and IC rates. In contrast, tone-plus-noise-driven channels would reduce MOC excitation, resulting in relatively higher cochlear gain, more saturation, and ultimately lower IC rates. Thus, the descending signal from IC BE cells to MOC is hypothesized to enhance contrast in the IC rate profile. Because efferents have slow dynamics, timing is an important factor. Therefore, we focus on model sensitivity to masked tones of different durations for comparison to psychophysical trends.

Developmental Synaptic Changes at the Transient Olivocochlear-Inner Hair Cell Synapse.

In the mature mammalian cochlea, inner hair cells (IHCs) are mainly innervated by afferent fibers that convey sound information to the CNS. During postnatal development, however, medial olivocochlear (MOC) efferent fibers transiently innervate the IHCs. The MOC-IHC synapse, functional from postnatal day 0 (P0) to hearing onset (P12), undergoes dramatic changes in the sensitivity to acetylcholine (ACh) and in the expression of key postsynaptic proteins. To evaluate whether there are associated changes in the properties of ACh release during this period, we used a cochlear preparation from mice of either sex at P4, P6-P7, and P9-P11 and monitored transmitter release from MOC terminals in voltage-clamped IHCs in the whole-cell configuration. The quantum content increased 5.6× from P4 to P9-P11 due to increases in the size and replenishment rate of the readily releasable pool of synaptic vesicles without changes in their probability of release or quantum size. This strengthening in transmission was accompanied by changes in short-term plasticity properties, which switched from facilitation at P4 to depression at P9-P11. We have previously shown that at P9-P11, ACh release is supported by P/Q- and N-type voltage-gated calcium channels (VGCCs) and negatively regulated by BK potassium channels activated by Ca2+ influx through L-type VGCCs. We now show that at P4 and P6-P7, release is mediated by P/Q-, R- and L-type VGCCs. Interestingly, L-type VGCCs have a dual role: they both support release and fuel BK channels, suggesting that at immature stages presynaptic proteins involved in release are less compartmentalized.SIGNIFICANCE STATEMENT During postnatal development before the onset of hearing, cochlear inner hair cells (IHCs) present spontaneous Ca2+ action potentials that release glutamate at the first auditory synapse in the absence of sound stimulation. The IHC Ca2+ action potential frequency pattern, which is crucial for the correct establishment and function of the auditory system, is regulated by the efferent medial olivocochlear (MOC) system that transiently innervates IHCs during this period. We show here that developmental changes in synaptic strength and synaptic plasticity properties at the MOC-IHC synapse upon MOC fiber activation at different frequencies might be crucial for tightly shaping the pattern of afferent activity during this critical period.

Auditory Attention Reduced Ear-Canal Noise in Humans by Reducing Subject Motion, Not by Medial Olivocochlear Efferent Inhibition: Implications for Measuring Otoacoustic Emissions During a Behavioral Task.

Otoacoustic emissions (OAEs) are often measured to non-invasively determine activation of medial olivocochlear (MOC) efferents in humans. Usually these experiments assume that ear-canal noise remains constant. However, changes in ear-canal noise have been reported in some behavioral experiments. We studied the variability of ear-canal noise in eight subjects who performed a two-interval-forced-choice (2IFC) sound-level-discrimination task on monaural tone pips in masker noise. Ear-canal noise was recorded directly from the unstimulated ear opposite the task ear. Recordings were also made with similar sounds presented, but no task done. In task trials, ear-canal noise was reduced at the time the subject did the discrimination, relative to the ear-canal noise level earlier in the trial. In two subjects, there was a decrease in ear-canal noise, primarily at 1–2 kHz, with a time course similar to that expected from inhibition by MOC activity elicited by the task-ear masker noise. These were the only subjects with spontaneous OAEs (SOAEs). We hypothesize that the SOAEs were inhibited by MOC activity elicited by the task-ear masker. Based on the standard rationale in OAE experiments that large bursts of ear-canal noise are artifacts due to subject movement, ear-canal noise bursts above a sound-level criterion were removed. As the criterion was lowered and more high- and moderate-level ear-canal noise bursts were removed, the reduction in ear-canal noise level at the time of the 2IFC discrimination decreased to almost zero, for the six subjects without SOAEs. This pattern is opposite that expected from MOC-induced inhibition (which is greater on lower-level sounds), but can be explained by the hypothesis that subjects move less and create fewer bursts of ear-canal noise when they concentrate on doing the task. In no-task trials for these six subjects, the ear-canal noise level was little changed throughout the trial. Our results show that measurements of MOC effects on OAEs must measure and account for changes in ear-canal noise, especially in behavioral experiments. The results also provide a novel way of showing the time course of the buildup of attention via the time course of the reduction in ear-canal noise.

Prestin Contributes to Membrane Compartmentalization and Is Required for Normal Innervation of Outer Hair Cells.

Outer hair cells (OHC) act as amplifiers and their function is modified by medial olivocochlear (MOC) efferents. The unique OHC motor protein, prestin, provides the molecular basis for somatic electromotility, which is required for sensitivity and frequency selectivity, the hallmarks of mammalian hearing. Prestin proteins are the major component of the lateral membrane of mature OHCs, which separates apical and basal domains. To investigate the contribution of prestin to this unique arrangement, we compared the distribution of membrane proteins in OHCs of wildtype (WT) and prestin-knockout (KO) mice. In WT, the apical protein PMCA2 was exclusively localized to the hair bundles, while it was also found at the lateral membrane in KOs. Similarly, a basal protein KCNQ4 did not coalesce at the base of OHCs but was widely dispersed in mice lacking prestin. Since the expression levels of PMCA2 and KCNQ4 remained unchanged in KOs, the data indicate that prestin is required for the normal distribution of apical and basal membrane proteins in OHCs. Since OHC synapses predominate in the basal subnuclear region, we also examined the synaptic architecture in prestin-KO mice. Although neurite densities were not affected, MOC efferent terminals in prestin-KO mice were no longer constrained to the basal pole as in WT. This trend was evident as early as at postnatal day 12. Furthermore, terminals were often enlarged and frequently appeared as singlets when compared to the multiple clusters of individual terminals in WT. This abnormality in MOC synaptic morphology in prestin-KO mice is similar to defects in mice lacking MOC pathway proteins such as α9/α10 nicotinic acetylcholine receptors and BK channels, indicating a role for prestin in the proper establishment of MOC synapses. To investigate the contribution of prestin’s electromotility, we also examined OHCs from a mouse model that expresses non-functional prestin (499-prestin). We found no changes in PMCA2 localization and MOC synaptic morphology in OHCs from 499-prestin mice. Taken together, these results indicate that prestin, independent of its motile function, plays an important structural role in membrane compartmentalization, which is required for the formation of normal efferent-OHC synapses in mature OHCs.

Olivocochlear Efferents in Animals and Humans: From Anatomy to Clinical Relevance.

Olivocochlear efferents allow the central auditory system to adjust the functioning of the inner ear during active and passive listening. While many aspects of efferent anatomy, physiology and function are well established, others remain controversial. This article reviews the current knowledge on olivocochlear efferents, with emphasis on human medial efferents. The review covers (1) the anatomy and physiology of olivocochlear efferents in animals; (2) the methods used for investigating this auditory feedback system in humans, their limitations and best practices; (3) the characteristics of medial-olivocochlear efferents in humans, with a critical analysis of some discrepancies across human studies and between animal and human studies; (4) the possible roles of olivocochlear efferents in hearing, discussing the evidence in favor and against their role in facilitating the detection of signals in noise and in protecting the auditory system from excessive acoustic stimulation; and (5) the emerging association between abnormal olivocochlear efferent function and several health conditions. Finally, we summarize some open issues and introduce promising approaches for investigating the roles of efferents in human hearing using cochlear implants.

Non-tip auditory-nerve responses that are suppressed by low-frequency bias tones originate from reticular lamina motion

Recent cochlear mechanical measurements show that active processes increase the motion response of the reticular lamina (RL) at frequencies more than an octave below the local characteristic frequency (CF) for CFs above 5 kHz. A possible correlate is that in high-CF (>5 kHz) auditory-nerve (AN) fibers, responses to frequencies 1-3 octaves below CF (“tail” frequencies) can be inhibited by medial olivocochlear (MOC) efferents. These results indicate that active processes enhance the sensitivity of tail-frequency RL and AN responses. Perhaps related is that some apical low-CF AN fibers have tuning-curve (TC) “side-lobe” response areas at frequencies above and below the TC-tip that are MOC inhibited. We hypothesized that the tail and side-lobe responses are enhanced by the same active mechanisms as CF cochlear amplification. If responses to CF, tail-frequency, and TC-side-lobe tones are all enhanced by prestin motility controlled by outer-hair-cell (OHC) transmembrane voltage, then they should depend on OHC stereocilia position in the same way. To test this, we cyclically changed the OHC-stereocilia mechano-electric-transduction (MET) operating point with low-frequency “bias” tones (BTs) and increased the BT level until the BT caused quasi-static OHC MET saturation that reduced or “suppressed” the gain of OHC active processes. While measuring cat AN-fiber responses, 50 Hz BT level series, 70–120 dB SPL, were run alone and with CF tones, or 2.5 kHz tail-frequency tones, or side-lobe tones. BT-tone-alone responses were used to exclude BT sound levels that produced AN responses that might obscure BT suppression. Data were analyzed to show the BT phase that suppressed the tone responses at the lowest sound level. We found that AN responses to CF, tail-frequency, and side-lobe tones were suppressed at the same BT phase in almost all cases. The data are consistent with the enhancement of responses to CF, tail-frequency, and side-lobe tones all being due to the same OHC-stereocilia MET-dependent active process. Thus, OHC active processes enhance AN responses at frequencies outside of the cochlear-amplified TC-tip region in both high- and low-frequency cochlear regions. The data are consistent with the AN response enhancements being due to enhanced RL motion that drives IHC-stereocilia deflection by traditional RL-TM shear and/or by changing the RL-TM gap. Since tail-frequency basilar membrane (BM) motion is not actively enhanced, the tail-frequency IHC drive is from a vibrational mode little present on the BM, not a “second filter” of BM motion.

A New Hypothesis on the Frequency Discrimination of the Cochlea.

Medial olivocochlear efferent (MOCE) neurons innervate outer hair cells (OHCs) of the cochlea, which in turn leads to basilar membrane motion. We hypothesized that MOCE-induced alterations in basilar membrane motion, independent of traveling waves, is responsible for the cochlear frequency discrimination of sound. Eleven guinea pigs underwent bilateral otoscopic and audiologic evaluations under general anesthesia. The study comprised two parts. Part I (n=11) included spontaneous otoacoustic emission (SOAE) recordings with or without contralateral pure-tone acoustic stimuli (1 and 8 kHz) at 60 dB sound pressure level (SPL). Part II involved pure-tone (1 or 8 kHz) acoustic trauma in the right ears of two randomly selected subgroups (G1: 1 kHz; n=4 and G8: 8 kHz; n=4). The remaining three animals served as controls. After frequency-specific deafness was confirmed by distortion product otoacoustic emission (DPOAE), SOAEs were recorded in the left ears in the presence of a contralateral pure-tone (1 and 8 kHz) stimulus of 60 dB SPL. Furthermore, the surface of the organ of Corti was examined by scanning electron microscopy (SEM). The contralateral pure tone led to frequency-specific activation in SOAEs in part I (without trauma) and part II (with trauma) measurements. SEM showed heterogeneous OHC damage along the cochlea in traumatized ears with pure tone. We suggest that MOCEs convey acoustic information from traumatized ears to intact ears. Traumatized ears can show frequency-specific activation in the presence of diffuse damage in OHCs that excludes the passive transmission of the pressure wave from the perilymph to the basilar membrane.

Spontaneous otoacoustic emission recordings during contralateral pure-tone activation of medial olivocochlear reflex.

We hypothesized that cochlear frequency discrimination occurs through medial olivocochlear efferent (MOCE)-induced alterations in outer hair cell (OHC) electromotility, which is independent from basilar membrane traveling waves. After obtaining informed consent, volunteers with normal hearing (n = 10; mean age: 20.6±1.2 years) and patients with unilateral deafness (n = 10; mean age: 30.2±17.9 years) or bilateral deafness (n = 8; mean age: 30.7±13.8 years) underwent a complete physical and audiological examination, and audiological tests including transient evoked otoacoustic emission and spontaneous otoacoustic emission (TEOAE and SOAE, respectively). SOAE recordings were performed during contralateral pure-tone stimuli at 1 and 3kHz. SOAE recordings in the presence of contralateral pure-tone stimuli showed frequency-specific activation out of the initial frequency range of SOAE responses. Basilar membrane motion during pure-tone stimulation results from OHC activation by means of MOCE neurons rather than from a traveling wave. Eventually, frequency-specific responses obtained from SOAEs suggested that OHC electromotility may be responsible for frequency discrimination of the cochlea independently from basilar membrane motion.