Olivocochlear Efferents Research Articles

Opposing expression gradients of calcitonin-related polypeptide alpha (Calca/Cgrpα) and tyrosine hydroxylase (Th) in type II afferent neurons of the mouse cochlea.

Type II spiral ganglion neurons (SGNs) are small caliber, unmyelinated afferents that extend dendritic arbors hundreds of microns along the cochlear spiral, contacting many outer hair cells (OHCs). Despite these many contacts, type II afferents are insensitive to sound and only weakly depolarized by glutamate release from OHCs. Recent studies suggest that type II afferents may be cochlear nociceptors, and can be excited by ATP released during tissue damage, by analogy to somatic pain-sensing C-fibers. The present work compares the expression patterns among cochlear type II afferents of two genes found in C-fibers: calcitonin-related polypeptide alpha (Calca/Cgrpα), specific to pain-sensing C-fibers, and tyrosine hydroxylase (Th), specific to low-threshold mechanoreceptive C-fibers, which was shown previously to be a selective biomarker of type II versus type I cochlear afferents (Vyas et al., ). Whole-mount cochlear preparations from 3-week- to 2-month-old CGRPα-EGFP (GENSAT) mice showed expression of Cgrpα in a subset of SGNs with type II-like peripheral dendrites extending beneath OHCs. Double labeling with other molecular markers confirmed that the labeled SGNs were neither type I SGNs nor olivocochlear efferents. Cgrpα starts to express in type II SGNs before hearing onset, but the expression level declines in the adult. The expression patterns of Cgrpα and Th formed opposing gradients, with Th being preferentially expressed in apical and Cgrpα in basal type II afferent neurons, indicating heterogeneity among type II afferent neurons. The expression of Th and Cgrpα was not mutually exclusive and co-expression could be observed, most abundantly in the middle cochlear turn.

Assessment of Ipsilateral Efferent Effects in Human via ECochG.

Development of electrophysiological means to assess the medial olivocochlear (MOC) system in humans is important to further our understanding of the function of that system and for the refinement and validation of psychoacoustical and otoacoustic emission methods which are thought to probe the MOC. Based on measurements in anesthetized animals it has been hypothesized that the MOC-reflex (MOCR) can enhance the response to signals in noise, and several lines of evidence support such a role in humans. A difficulty in these studies is the isolation of efferent effects. Efferent activation can be triggered by acoustic stimulation of the contralateral or ipsilateral ear, but ipsilateral stimulation is thought to be more effective. However, ipsilateral stimulation complicates interpretation of effects since these sounds can affect the perception of other ipsilateral sounds by mechanisms not involving olivocochlear efferents. We assessed the ipsilaterally evoked MOCR in human using a transtympanic procedure to record mass-potentials from the cochlear promontory or the niche of the round window. Averaged compound action potential (CAP) responses to masked probe tones of 4 kHz with and without a precursor (designed to activate the MOCR but not the stapedius reflex) were extracted with a polarity alternating paradigm. The masker was either a simultaneous narrow band noise masker or a short (20-ms) tonal ON- or OFF-frequency forward masker. The subjects were screened for normal hearing (audiogram, tympanogram, threshold stapedius reflex) and psychoacoustically tested for the presence of a precursor effect. We observed a clear reduction of CAP amplitude by the precursor, for different masking conditions. Even without an MOCR, this is expected because the precursor will affect the response to subsequent stimuli via neural adaptation. To determine whether the precursor also activated the efferent system, we measured the CAP over a range of masker levels, with or without precursor, and for different types of masker. The results show CAP reduction consistent with the type of gain reduction caused by the MOCR. These results generally support psychoacoustical paradigms designed to probe the efferent system as indeed activating the MOCR system, but not all observations are consistent with this mechanism.

Musicianship enhances ipsilateral and contralateral efferent gain control to the cochlea

Human hearing sensitivity is easily compromised with overexposure to excessively loud sounds, leading to permanent hearing damage. Consequently, finding activities and/or experiential factors that distinguish “tender” from “tough” ears (i.e., acoustic vulnerability) would be important for identifying people at higher risk for hearing damage. To regulate sound transmission and protect the inner ear against acoustic trauma, the auditory system modulates gain control to the cochlea via biological feedback of the medial olivocochlear (MOC) efferents, a neuronal pathway linking the lower brainstem and cochlear outer hair cells. We hypothesized that a salient form of auditory experience shown to have pervasive neuroplastic benefits, namely musical training, might act to fortify hearing through tonic engagement of these reflexive pathways. By measuring MOC efferent feedback via otoacoustic emissions (cochlear emitted sounds), we show that dynamic ipsilateral and contralateral cochlear gain control is enhanced in musically-trained individuals. Across all participants, MOC strength was correlated with the years of listeners' training suggested that efferent gain control is experience dependent. Our data provide new evidence that intensive listening experience(s) (e.g., musicianship) can strengthen the ipsi/contralateral MOC efferent system and sound regulation to the inner ear. Implications for reducing acoustic vulnerability to damaging sounds are discussed.

Electrically Evoked Medial Olivocochlear Efferent Effects on Stimulus Frequency Otoacoustic Emissions in Guinea Pigs.

Stimulus frequency otoacoustic emissions (SFOAEs) are produced by cochlear irregularities reflecting energy from the peak region of the traveling wave (TW). Activation of medial olivocochlear (MOC) efferents reduces cochlear amplification and otoacoustic emissions (OAEs). In other OAEs, MOC activation can produce enhancements. The extent of MOC enhancements of SFOAEs has not been previously studied. In anesthetized guinea pigs, we electrically stimulated MOC fibers and recorded their effects on SFOAEs. MOC stimulation mostly inhibited SFOAEs but sometimes enhanced them. Some enhancements were not near response dips and therefore cannot be explained by a reduction of wavelet cancelations. MOC stimulation always inhibited auditory-nerve compound action potentials showing that cochlear-amplifier gain was not increased. We propose that some SFOAE enhancements arise because shocks excite only a small number of MOC fibers that inhibit a few scattered outer hair cells thereby changing (perhaps increasing) cochlear irregularities and SFOAE amplitudes. Contralateral sound activation is expected to excite approximately one third of MOC efferents and may also change cochlear irregularities. Some papers suggest that large SFOAE components originate far basal of the TW peak, basal of the region that receives cochlear amplification. Using a time-frequency analysis, we separated SFOAEs into components with different latencies. At all SFOAE latencies, most SFOAE components were inhibited by MOC stimulation, but some were enhanced. The MOC inhibition of short-latency SFOAE components is consistent with these components being produced in the cochlear-amplified region near the TW peak.

Modeling the effect of olivocochlear efferents on the subcortical envelope following response in humans

The medial olivocochlear reflex (MOCR), a feedback mechanism that controls outer-hair-cell gain, is thought to provide protection and signal enhancement for a listener in background noise. This listening advantage can be attributed to reduced auditory-nerve firing to noise, which results in an increased dynamic range for encoding signals of interest. The computational model presented here updates the modeling work of Smalt et al. (2014) by adding dynamic MOCR characteristics to the more recent “humanized” model version (Zilany, et al., 2014). This MOCR implementation effectively reduces outer-hair-cell gain depending on the stimulus frequency, level, and timing. Human Envelope Following Responses (EFRs; Bharadwaj, 2015) were compared to outputs of the Nelson and Carney (2004) Inferior-Colliculus (IC) model combined with the MOCR auditory-nerve model. Adding simultaneous contralateral noise did not significantly affect the model IC modulation-filter energy at the stimulus frequency, while a 500-ms contrala...

Descending projections from the inferior colliculus to medial olivocochlear efferents: Mice with normal hearing, early onset hearing loss, and congenital deafness

Auditory efferent neurons reside in the brain and innervate the sensory hair cells of the cochlea to modulate incoming acoustic signals. Two groups of efferents have been described in mouse and this report will focus on the medial olivocochlear (MOC) system. Electrophysiological data suggest the MOC efferents function in selective listening by differentially attenuating auditory nerve fiber activity in quiet and noisy conditions. Because speech understanding in noise is impaired in age-related hearing loss, we asked whether pathologic changes in input to MOC neurons from higher centers could be involved. The present study investigated the anatomical nature of descending projections from the inferior colliculus (IC) to MOCs in 3-month old mice with normal hearing, and in 6-month old mice with normal hearing (CBA/CaH), early onset progressive hearing loss (DBA/2), and congenital deafness (homozygous Shaker-2). Anterograde tracers were injected into the IC and retrograde tracers into the cochlea. Electron microscopic analysis of double-labelled tissue confirmed direct synaptic contact from the IC onto MOCs in all cohorts. These labelled terminals are indicative of excitatory neurotransmission because they contain round synaptic vesicles, exhibit asymmetric membrane specializations, and are co-labelled with antibodies against VGlut2, a glutamate transporter. 3D reconstructions of the terminal fields indicate that in normal hearing mice, descending projections from the IC are arranged tonotopically with low frequencies projecting laterally and progressively higher frequencies projecting more medially. Along the mediolateral axis, the projections of DBA/2 mice with acquired high frequency hearing loss were shifted medially towards expected higher frequency projecting regions. Shaker-2 mice with congenital deafness had a much broader spatial projection, revealing abnormalities in the topography of connections. These data suggest that loss in precision of IC directed MOC activation could contribute to impaired signal detection in noise.

Induced Loudness Reduction and Enhancement in Acoustic and Electric Hearing.

The loudness of a tone can be reduced by preceding it with a more intense tone. This effect, known as induced loudness reduction (ILR), has been reported to last for several seconds. The underlying neural mechanisms are unknown. One possible contributor to the effect involves changes in cochlear gain via the medial olivocochlear(MOC) efferents. Since cochlear implants (CIs) bypass the cochlea, investigating whether and how CI users experience ILR should help provide a better understanding of the underlying mechanisms. In the present study, ILR was examined in both normal-hearing listeners and CI users by examining the effects of an intense precursor (50 or 500ms) on the loudness of a 50-ms target, as judged by comparing it to a spectrally remote 50-ms comparison sound. The interstimulus interval (ISI) between the precursor and the target was varied between 10 and 1000ms to estimate the time course of ILR. In general, the patterns of results from the CI users were similar to those found in the normal-hearing listeners. However, in the short-precursor short-ISI condition, an enhancement in the loudness of target was observed in CI subjects that was not present in the normal-hearing listeners, consistent with the effects of an additional attenuation present in the normal-hearing listeners but not in the CI users. The results suggest that the MOC may play a role but that it is not the only source of these loudness context effects.

Efferent Modulation of Stimulus Frequency Otoacoustic Emission Fine Structure.

Otoacoustic emissions, sounds generated in the inner ear, have become a convenient non-invasive tool to examine the efferent modulation of cochlear mechanics. Activation of the medial olivocochlear (MOC) efferents has been shown to alter the magnitude of these emissions. When the effects of efferent activation on the detailed spectral structures of these emissions have been examined, a shift of the spectral patterns toward higher frequencies has been reported for distortion product and spontaneous otoacoustic emissions. Stimulus frequency otoacoustic emissions (SFOAEs) have been proposed as the preferred emission type in the study of efferent modulation due to the simplicity of their production leading to the possibility of clearer interpretation of results. The effects of efferent activation on the complex spectral patterns of SFOAEs have not been examined to the best of our knowledge. We have examined the effects of activating the MOC efferents using broadband noise in normal-hearing humans. The detailed spectral structure of SFOAEs, known as fine structure, was recorded with and without contralateral acoustic stimulation. Results indicate that SFOAEs are reduced in magnitude and their fine structure pushed to higher frequencies by contralateral acoustic stimulation. These changes are similar to those observed in distortion product or spontaneous otoacoustic emissions and behavioral hearing thresholds. Taken together with observations made about magnitude and phase changes in otoacoustic emissions and hearing thresholds upon contralateral acoustic stimulation, all changes in otoacoustic emission and hearing threshold fine structure appear to be driven by a common set of mechanisms. Specifically, frequency shifts in fine structure patterns appear to be linked to changes in SFOAE phase due to contralateral acoustic stimulation.

Adenomatous Polyposis Coli Protein Deletion in Efferent Olivocochlear Neurons Perturbs Afferent Synaptic Maturation and Reduces the Dynamic Range of Hearing.

This study identifies novel molecules and cellular interactions that are essential for the proper maturation of afferent ribbon synapses in sensory cells of the inner ear, and for normal hearing.

Right-ear advantage drives the link between olivocochlear efferent 'antimasking' and speech-in-noise listening benefits.

The mammalian cochlea receives feedback from the brainstem medial olivocochlear (MOC) efferents, whose putative 'antimasking' function is to adjust cochlear amplification and enhance peripheral signal detection in adverse listening environments. Human studies have been inconsistent in demonstrating a clear connection between this corticofugal system and behavioral speech-in-noise (SIN) listening skills. To elucidate the role of brainstem efferent activity in SIN perception, we measured ear-specific contralateral suppression of transient-evoked otoacoustic emissions (OAEs), a proxy measure of MOC activation linked to auditory learning in noisy environments. We show that suppression of cochlear emissions is stronger with a more basal cochlear bias in the right ear compared with the left ear. Moreover, a strong negative correlation was observed between behavioral SIN performance and right-ear OAE suppression magnitudes, such that lower speech reception thresholds in noise were predicted by larger amounts of MOC-related activity. This brain-behavioral relation was not observed for left ear SIN perception. The rightward bias in contralateral MOC suppression of OAEs, coupled with the stronger association between physiological and perceptual measures, is consistent with left-hemisphere cerebral dominance for speech-language processing. We posit that corticofugal feedback from the left cerebral cortex through descending MOC projections sensitizes the right cochlea to signal-in-noise detection, facilitating figure-ground contrast and improving degraded speech analysis. Our findings demonstrate that SIN listening is at least partly driven by subcortical brain mechanisms; primitive stages of cochlear processing and brainstem MOC modulation of (right) inner ear mechanics play a critical role in dictating SIN understanding.

Contralateral masking in bilateral cochlear implant patients: a model of medial olivocochlear function loss.

Contralateral masking is the phenomenon where a masker presented to one ear affects the ability to detect a signal in the opposite ear. For normal hearing listeners, contralateral masking results in masking patterns that are both sharper and dramatically smaller in magnitude than ipsilateral masking. The goal of this study was to investigate whether medial olivocochlear (MOC) efferents are needed for the sharpness and relatively small magnitude of the contralateral masking function. To do this, bilateral cochlear implant patients were tested because, by directly stimulating the auditory nerve, cochlear implants circumvent the effects of the MOC efferents. The results indicated that, as with normal hearing listeners, the contralateral masking function was sharper than the ipsilateral masking function. However, although there was a reduction in the magnitude of the contralateral masking function compared to the ipsilateral masking function, it was relatively modest. This is in sharp contrast to the results of normal hearing listeners where the magnitude of the contralateral masking function is greatly reduced. These results suggest that MOC function may not play a large role in the sharpness of the contralateral masking function but may play a considerable role in the magnitude of the contralateral masking function.

Molecular interaction of α-conotoxin RgIA with the rat α9α10 nicotinic acetylcholine receptor.

The α9α10 nicotinic acetylcholine receptor (nAChR) was first identified in the auditory system, where it mediates synaptic transmission between efferent olivocochlear cholinergic fibers and cochlea hair cells. This receptor gained further attention due to its potential role in chronic pain and breast and lung cancers. We previously showed that α-conotoxin (α-CTx) RgIA, one of the few α9α10 selective ligands identified to date, is 300-fold less potent on human versus rat α9α10 nAChR. This species difference was conferred by only one residue in the (-), rather than (+), binding region of the α9 subunit. In light of this unexpected discovery, we sought to determine other interacting residues with α-CTx RgIA. A previous molecular modeling study, based on the structure of the homologous molluscan acetylcholine-binding protein, predicted that RgIA interacts with three residues on the α9(+) face and two residues on the α10(-) face of the α9α10 nAChR. However, mutations of these residues had little or no effect on toxin block of the α9α10 nAChR. In contrast, mutations of homologous residues in the opposing nAChR subunits (α10 Ε197, P200 and α9 T61, D121) resulted in 19- to 1700-fold loss of toxin activity. Based on the crystal structure of the extracellular domain (ECD) of human α9 nAChR, we modeled the rat α9α10 ECD and its complexes with α-CTx RgIA and acetylcholine. Our data support the interaction of α-CTx RgIA at the α10/α9 rather than the α9/α10 nAChR subunit interface, and may facilitate the development of selective ligands with therapeutic potential.

The biological role of the medial olivocochlear efferents in hearing: separating evolved function from exaptation.

Cochlear outer hair cells (OHCs) are remarkable, mechanically-active receptors that determine the exquisite sensitivity and frequency selectivity characteristic of the mammalian auditory system. While there are three to four times as many OHCs compared with inner hair cells, OHCs lack a significant afferent innervation and, instead, receive a rich efferent innervation from medial olivocochlear (MOC) efferent neurons. Activation of the MOC has been shown to exert a considerable suppressive effect over OHC activity. The precise function of these efferent tracts in auditory behavior, however, is the matter of considerable debate. The most frequent functions assigned to the MOC tracts are to protect the cochlea from traumatic damage associated with intense sound and to aid the detection of signals in noise. While considerable evidence shows that interruption of MOC activity exacerbates damage due to high-level sound exposure, the well characterized MOC physiology and evolutionary studies do not support such a role. Instead, a MOC protective effect is well explained as being a byproduct of the suppressive nature of MOC action on OHC mechanical behavior. A role in the enhancement of signals in noise backgrounds, on the other hand, is well supported by (1) an extensive physiological literature (2) examination of naturally occurring environmental acoustic conditions (3) recent data from multiple laboratories showing that the MOC plays a significant role in auditory selective attention by suppressing the response to unattended or ignored stimuli. This presentation will argue that, based on the extant literature combining the suppression of background noise through MOC-mediated rapid adaptation (RA) with the suppression of non-attended signals, in concert with the corticofugal pathways descending from the auditory cortex, the MOC system has one evolved function—to increase the signal-to-noise ratio, aiding in the detection of target signals. By contrast, the MOC system role in reducing noise damage and the effects of aging in the cochlea may well represent an exaptation, or evolutionary “spandrel”.

Contralateral efferent suppression of human hearing sensitivity.

The present study aimed at characterizing the suppressing effect of contralateral medial olivocochlear (MOC) efferents on human auditory sensitivity and mechanical cochlear responses at sound levels near behavioral thresholds. Absolute thresholds for pure tones of 500 and 4000 Hz with durations between 10–500 ms were measured in the presence and in the absence of a contralateral broadband noise. The intensity of the noise was fixed at 60 dB SPL to evoke the contralateral MOC reflex without evoking the middle-ear muscle reflex. In agreement with previously reported findings, thresholds measured without the contralateral noise decreased with increasing tone duration, and the rate of decrease was faster at 500 than at 4000 Hz. Contralateral stimulation increased thresholds by 1.07 and 1.72 dB at 500 and 4000 Hz, respectively. The mean increase (1.4 dB) just missed statistical significance (p = 0.08). Importantly, the across-frequency mean threshold increase was significantly greater for long than for short probes. This effect was more obvious at 4000 Hz than at 500 Hz. Assuming that thresholds depend on the MOC-dependent cochlear mechanical response followed by an MOC-independent, post-mechanical detection mechanism, the present results at 4000 Hz suggest that MOC efferent activation suppresses cochlear mechanical responses more at lower than at higher intensities across the range of intensities near threshold, while the results at 500 Hz suggest comparable mechanical suppression across the threshold intensity range. The results are discussed in the context of central masking and of auditory models of efferent suppression of cochlear mechanical responses.

Prickle1 is necessary for the caudal migration of murine facial branchiomotor neurons.

Facial branchiomotor neurons (FBMs) of vertebrates typically develop in rhombomere 4 (r4), and in mammals and several other vertebrate taxa, migrate caudally into r6 and subsequently laterally and ventrally to the pial surface. How similar or dissimilar these migratory processes between species are at a molecular level remains unclear. In zebrafish and mouse, mutations in certain PCP genes disrupt normal caudal migration of FBMs. Zebrafish prickle1a (prickle-like 1a) and prickle1b, two orthologs of Prickle1, act non-cell-autonomously and cell-autonomously, respectively, to regulate FBM migration. Here, we show that, in Prickle1 (C251X/C251X) mice which have reduced Prickle1 expression, the caudal migration of FBMs is affected. Most FBM neurons do not migrate caudally along the floor plate. However, some neurons perform limited caudal migration such that the neurons eventually lie near the pial surface from r4 to anterior r6. FBMs in Prickle1 (C251X/C251X) mice survive until P0 and form an ectopic nucleus dorsal to the olivo-cochlear efferents of r4. Ror2, which modifies the PCP pathway in other systems, is expressed by the migrating mouse FBMs, but is not required for FBM caudal migration. Our results suggest that, in mice, Prickle1 is part of a molecular mechanism that regulates FBM caudal migration and separates the FBM and the olivo-cochlear efferents. This defective caudal migration of FBMs in Prickle1C251X mutants resembles Vangl2 mutant defects. In contrast to other developing systems that show similar defects in Prickle1, Wnt5a and Ror2, the latter two only have limited or no effect on FBM caudal migration.

Olivocochlear innervation maintains the normal modiolar-pillar and habenular-cuticular gradients in cochlear synaptic morphology.

Morphological studies of inner hair cell (IHC) synapses with cochlear nerve terminals have suggested that high- and low-threshold fibers differ in the sizes of their pre- and postsynaptic elements as well as the position of their synapses around the hair cell circumference. Here, using high-power confocal microscopy, we measured sizes and spatial positions of presynaptic ribbons, postsynaptic glutamate receptor (GluR) patches, and olivocochlear efferent terminals at eight locations along the cochlear spiral in normal and surgically de-efferented mice. Results confirm a prior report suggesting a modiolar > pillar gradient in ribbon size and a complementary pillar > modiolar gradient in GluR-patch size. We document a novel habenular < cuticular gradient in GluR patch size and a complementary cuticular < habenular gradient in olivocochlear innervation density. All spatial gradients in synaptic elements collapse after cochlear de-efferentation, suggesting a major role of olivocochlear efferents in maintaining functional heterogeneity among cochlear nerve fibers. Our spatial analysis also suggests that adjacent IHCs may contain a different synaptic mix, depending on whether their tilt in the radial plane places their synaptic pole closer to the pillar cells or to the modiolus.

Dynorphin release by the lateral olivocochlear efferents may inhibit auditory nerve activity: A cochlear drug delivery study

Dynorphin (dyn) is suggested to excite the auditory nerve (AN) when released by the lateral olivocochlear (LOC) efferents. However, previous studies evaluated either intravenously delivered dyn-like agents, raising the potential for systemic (central) effects, or agent concentrations unlikely to be achieved via endogenous cochlear release. This study tested the hypothesis that biologically relevant increases in dyn levels in the cochlea achieved via diffusion of the drug of (−)pentazocine across the round window membrane enhances AN firing. In general, amplitude of the cochlear whole-nerve action potential (CAP) was depressed following drug application. These results suggest that dyn released by the LOC neurons would likely act as an inhibitory transmitter substance in the LOC system; neurotransmission is one of the LOC system's vast unknowns.

Challenges in exploring the role of medial olivocochlear efferents in auditory tasks via otoacoustic emissions

A number of recent psychophysical studies have hypothesized that the activation of medial olivocochlear (MOC) efferents plays a significant role in forward masking. These hypotheses are based on general similarities between spectral and temporal characteristics exhibited by some psychophysical forward-masking results and by effects of efferent activation measured using physiological methods. In humans, noninvasive physiological measurements of otoacoustic emissions have been used to probe changes in cochlear responses due to MOC efferent activation. The aim of this study was to verify our earlier efferent-based hypothesis regarding the dependence of psychophysical forward masking of a 6-kHz probe on the phase curvature of harmonic-complex maskers. The ear-canal pressure for a continuous 6-kHz probe was measured in the presence and absence of Schroeder-phase complexes used as forward maskers in our previous psychophysical study. Changes in the ear-canal pressure were analyzed using methods for estimating the effects of efferent activation on stimulus frequency otoacoustic emissions under the assumption that changes in cochlear gain due to efferent activation will be reflected in changes in the magnitude and phase of the emission. Limitations and challenges in relating effects of feedback-based reflexes to psychophysical effects will be discussed. [Work supported by NIH grant R01DC010374.]

Mice with chronic medial olivocochlear dysfunction do not perform as predicted by common hypotheses about the role of efferent cochlear feedback in hearing

Mice missing the alpha9 nicotinic acetylcholine receptor subunit (A9KO) show a lack of classic efferent effects on cochlear activity; however, behavioral and physiological studies in these mice have failed to support common hypotheses about the role of efferent feedback in auditory function. A9KO mice do not show deficits detecting or discriminating tones in noise. These mice also do not appear to be more susceptible to age-related hearing loss, and they do not show increased auditory brainstem response thresholds when chronically exposed to moderate-level noise. A9KO mice do show increased susceptibility to temporal processing deficits, especially when exposed to environmental noise. Furthermore, A9KO mice show extremely variable, and sometimes poor, performance when discriminating changes in the location of broadband sounds in the horizontal plane. Temporal and spatial processing deficits may be attributable to abnormal or poorly optimized representation of acoustic cues in the central auditory pathways. These results are consistent with experiments in humans that suggest artificial stimulation of medial olivocochlear efferents overestimates the actual activation of these pathways. Thus, the primary role of medial olivocochlear efferent feedback may be to regulate input from the cochlea to the brain (and within the brain) to maintain an optimal, calibrated representation of sounds.

Shelter from the Glutamate storm: Loss of olivocochlear efferents increases cochlear nerve degeneration during aging

The olivocochlear (OC) feedback pathways include one population, the medial (M)OC projections to outer hair cells, which forms a sound-evoked inhibitory reflex that can reduce sound-induced cochlear vibrations, and a second population, the lateral (L)OC projections to the synaptic zone underneath the inner hair cells, that can modulate the excitability of the cochlear nerve terminals. Although there is ample evidence of OC-mediated protective effects from both of these systems when the ear is exposed to intense noise, the functional significance of this protection is questionable in a pre-industrial environment where intense noise was not so commonplace. We have re-evaluated the phenomenon of OC-mediated protection in light of recent work showing that acoustic exposure destroys cochlear neurons at sound pressure levels previously considered atraumatic, because they cause no permanent hair cell loss or threshold shift. We have shown that loss of OC innervation at a young age causes the cochlea to age a greatly accelerated rate, even without purposeful noise exposure, when aging is measured by the loss of synaptic connections between cochlear nerve fibers and hair cells. Possible relevance to hearing-in-noise problems of the elderly will be discussed.