Electrical stimulation of the inferior colliculus at low rates protects the cochlea from auditory desensitization

The effects of inferior collicular (IC) stimulation on cochlear responses were tested with pulsed electrical trains and with 1 min long continuous bursts. Pulsed trains did not cause any effects at the contralateral cochlea. However, a 1 min burst, containing pulses at low rates, was able to significantly reduce temporary threshold shifts (TTS) in cochlear sensitivity caused by a loud sound exposure. Intracochlear perfusion of hexamethonium blocked this effect. The time course of the hexamethonium blocking action paralleled its blocking action on the cochlear effects of electrical stimulation at the brainstem of an auditory efferent pathway, the crossed olivocochlear bundle (COCB). The protective IC effects were persistent and TTS reductions could be obtained even with a 5 min delay between IC stimulus and the loud sound. However, these persistent protective effects did not appear to occur at the cochlea. Finally, electrical stimulation at the IC ipsilateral to a cochlea exposed to loud sound also reduced TTS, but only by smaller amounts and at higher stimulation rates. Thus the IC appears to provide a strong descending influence that modulates the excitability levels of the olivocochlear nuclei in the brainstem. Both crossed and uncrossed OCB appear to be involved and able to reduce TTS. It is proposed that the protective effects may be due solely to the medial olivocochlear system and possibly only those fibres originating from one of the nuclei of the medial system.     

Binaural acoustic stimulation exercises protective effects at the cochlea that mimic the effects of electrical stimulation of an auditory efferent pathway

Low-level acoustic stimulation of one (contralateral) ear reduced the neural desensitization caused by a simultaneous loud sound exposure in the other (ipsilateral) ear in a loss-related manner. Greatest reductions in the temporary threshold shifts (TTS) in the exposed ear were obtained when the exposure would have caused large amounts of TTS. Low-level exposures (reduced intensity or duration of exposure) which caused low levels of TTS, from which the cochlea could recover relatively quickly, were not affected by the contralateral stimulus. Intermediate levels of TTS showed intermediate levels of reduction for the same contralateral acoustic stimulus. These effects were similar to effects previously demonstrated with electrical stimulation of an efferent pathway to the cochlea, the crossed olivocochlear bundle (COCB); lesioning the COCB prevented the contralateral stimulus from having any effect on TTS due to an ipsilateral exposure. Like COCB stimulation, the contralateral acoustic stimulus had tonic effects, so that reductions in ipsilateral TTS could be obtained even when the contralateral stimulus was presented 5 min before the ipsilateral exposure. With 10 min delay no effect on TTS occurred. The contralateral stimulus did not appear to cause any changes in responses in the ipsilateral cochlea prior to the loud sound exposure. These results are discussed as indicating an interaction between the two inputs at a central locus, leading to activation of the COCB fibres to the cochlea exposed to the loud sound.     

Centrifugal pathways protect hearing sensitivity at the cochlea in noisy environments that exacerbate the damage induced by loud sound.

Loud sounds damage the cochlea, the auditory receptor organ, reducing hearing sensitivity. Previous studies demonstrate that the centrifugal olivocochlear pathways can moderately reduce these temporary threshold shifts (TTSs), protecting the cochlea. This effect involves only the olivocochlear pathway component known as the crossed medial olivocochlear system pathway, originating from the contralateral brainstem and terminating on outer hair cells in the cochlea. Here I demonstrate that even moderate noise backgrounds can significantly exacerbate the cochlear TTSs induced by loud tones, but this is prevented because in such conditions there is additional activation of uncrossed olivocochlear pathways, enhancing protection of cochlear hearing sensitivity. Activation of the uncrossed pathways differs from that of the crossed pathway in that it is achieved only in noise backgrounds but can then be obtained under monaural conditions of loud tone and background noise. In contrast, activation of the crossed pathway is achieved only by binaural loud tones and is not further enhanced by background noise. Thus, conjoint activation of both crossed and uncrossed efferent pathways can occur in noise backgrounds to powerfully protect the cochlea under conditions similar to those encountered naturally by humans.     

Bandwidth determines modulatory effects of centrifugal pathways on cochlear hearing desensitization caused by loud sound

Centrifugal olivocochlear (OC) pathways modulate cochlear hearing losses induced in cats by loud sounds varying in bandwidth from tones to clicks and noise bands, in a variety of conditions. The general effect, always to reduce hearing damage, can be a net effect resulting from complex interactions between OC subcomponents (crossed and uncrossed OC pathways). The interactions between these subcomponents vary with type of loud sound, suggesting that sound bandwidth may be important in determining how OC pathways modulate loud sound-induced hearing loss. This dependency was examined and here it is reported that OC pathways do not alter cochlear hearing losses caused by loud noise with a 2-kHz-wide bandwidth intermediate between the loud sounds of previous studies. Increasing stimulus bandwidth even slightly more, to use a loud 3.5-kHz-wide bandwidth noise as the damaging sound, once again revealed OC modulation of cochlear hearing loss. The fact that OC pathways do not modulate cochlear hearing losses induced by loud 2-kHz-wide noise was demonstrated in three very different test conditions in which OC pathways modulate hearing losses caused by narrower or broader bandwidth sounds. This confirmed that the absence of centrifugal modulation of hearing loss to this particular sound was a robust phenomenon not related to test condition. The absence of overall centrifugal effects was also true at the level of subcomponent pathways; neither crossed nor uncrossed OC pathways individually modulated cochlear hearing losses to the loud 2-kHz-wide noise. This surprising frequency dependency has general implications for centrifugal modulation of cochlear responses.     

Selective retrograde labeling of lateral olivocochlear neurons in the brainstem based on preferential uptake of 3H-D-aspartic acid in the cochlea

We have previously shown that perfusion of the gerbil cochlea with probe concentrations of 3H-D-aspartic acid (D-ASP) results in immediate, selective labeling of 50-60% of the efferent terminals under the inner hair cells, presumably by high-affinity uptake. The present study was undertaken to determine the origin of these endings. Twenty-four hours after cochlear perfusion with D-ASP, labeled neurons were observed in the ipsilateral, and to a much lesser extent in the contralateral, lateral superior olivary nucleus (LSO). The cells were small, primarily fusiform, and showed fewer synaptic contacts than other LSO cells. Combined transport of D-ASP and horseradish peroxidase indicated that all olivocochlear neurons within the LSO that projected to the injected cochlea were labeled by D-ASP. Labeled fibers coursed dorsally from the LSO, joined contralateral fibers that had passed under the floor of the fourth ventricle, and entered the VIIIth nerve root at its ventromedial edge. Adjacent to the ventral cochlear nucleus (VCN), densely labeled collateral fibers crossed the nerve root to enter the VCN. Labeled fibers and terminals were prominent in the central VCN. Neither retrograde transport of D-ASP by medial olivocochlear and vestibular efferents nor anterograde transport by VIIIth nerve afferents was observed. The D-ASP-labeled cells and fibers are clearly lateral olivocochlear efferents. Retrograde transport of D-ASP thus allows the cells, axons, and collaterals of the lateral olivocochlear system to be studied, morphologically, in isolation from other cells that project to the cochlea. Since the olivocochlear neurons are almost certainly cholinergic, retrograde amino acid transport does not necessarily identify the primary neurotransmitter of a neuron. Rather, it indicates the presence of selective uptake by the processes of that neuron at the site of amino acid injection. Retrograde labeling appears to be markedly enhanced by the use of metabolically inert compounds such as d-isomer amino acids.     

Long-term sound conditioning increases distortion product otoacoustic emission amplitudes and decreases olivocochlear efferent reflex strength

The cochlea can be protected from acoustic trauma by moderate-level sound exposure. It is suggested that olivocochlear system may play a significant role in this protection. This study was performed to investigate distortion product otoacoustic emission (DPOAE) amplitudes changes and the efficiency of contralateral noise stimulation on DPOAE after conditioning noise exposure. Our results demonstrate that long-term conditioning can increase the DPOAE amplitudes at low frequencies (1.0-3.0 kHz) and decrease the olivocochlear efferent reflex strength at the same frequencies. The DPOAE amplitudes are partially restored to the preconditioning levels 2 weeks after conditioning; contralateral suppression also returns to the preconditioning levels. These results suggest that the enhancement of DPOAE amplitudes might be due to a decrease in olivocochlear efferent reflex strength.     

Noise trauma alters D-[3H]aspartate release and AMPA binding in chinchilla cochlear nucleus

Exposure of adults to loud noise can overstimulate the auditory system, damage the cochlea, and destroy cochlear nerve axons and their synaptic endings in the brain. Cochlear nerve loss probably results from the death of cochlear inner hair cells (IHC). Additional degeneration in the cochlear nucleus (CN) is hypothesized to stem from overstimulation of the system, which may produce excitotoxicity. This study tested these predictions by exposing one ear of anesthetized adult chinchillas to a loud noise, which damaged the ipsilateral cochlea and induced degeneration in the glutamatergic cochlear nerve. During the first postexposure week, before cochlear nerve axons degenerated, glutamatergic synaptic release in the ipsilateral CN was elevated and uptake was depressed, consistent with hyperactivity of glutamatergic transmission and perhaps with the operation of an excitotoxic mechanism. By 14 days, when cochlear nerve fibers degenerated, glutamatergic synaptic release and uptake in the CN became deficient. By 90 days, a resurgence of transmitter release and an elevation of AMPA receptor binding suggested transmission upregulation through plasticity that resembled changes after mechanical cochlear damage. These changes may contribute to tinnitus and other pathologic symptoms that precede and accompany hearing loss. In contrast, the other ear, protected with a silicone plug during the noise exposure, exhibited virtually no damage in the cochlea or the cochlear nerve. Altered glutamatergic release and AMPA receptor binding activity in the CN suggested upregulatory plasticity driven by signals emanating from the CN on the noise-exposed side.     

Efferent-mediated protection of the cochlear base from acoustic overexposure by low doses of lithium

Many studies on anaesthetized animals and a few on awake animals have suggested that the cholinergic olivocochlear efferent feedback to outer hair cells can participate in the protection of the cochlea from acoustic overexposure. Lithium is known to stimulate acetylcholine synthesis and release in the brain and it is likely to act similarly at the level of the cochlear efferent synapses. We demonstrate here that, in the awake guinea-pig with a chronically implanted electrode on the round window of the cochlea, the temporary threshold shift induced by 1 minute exposure to different pure tones at around 90 dB sound pressure level (SPL) was reduced by as much as 40 dB, when exposure occurred after lithium treatment. The protection effect was not observed in anaesthetized animals. The effect was seen across the test frequency range of 6.4–12.5 kHz, suggesting that both ‘fast’ and ‘slow’ efferent effects are likely to be mediated by acetylcholine. Together our results provide new evidence that the olivocochlear efferents can provide a more efficient protection from acoustic overexposure when animals are awake.     

Olivocochlear efferent vs. middle-ear contributions to the alteration of otoacoustic emissions by contralateral noise

The medial olivocochlear efferent bundle is the key element of a bilateral efferent reflex activated by sound in either ear and acting directly on cochlear outer hair cells (OHC) via numerous cholinergic synapses. It probably contributes to regulating the mechanical activity of the cochlea. Otoacoustic emissions, being sounds emitted by the cochlea as a reflection of its activity and suppressed by efferent activation, are increasingly considered to be the privileged tool for a noninvasive assessment of the efferent reflex. However, confounding effects on otoacoustic emissions can occur. A primary influence is middle-ear muscle reflex activation, which shares common features with the effects of cochlear efferent activation. We report a systematic comparison of the responses of human otoacoustic emissions to efferent activation by low-level noise in the contralateral ear to various middle-ear manipulations (reflex contractions of the stapedius muscle induced by high-level contralateral noise; moderate middle-ear pressure changes). The profiles of level and phase changes of otoacoustic emissions as a function of frequency were highly specific to the origin of the effects. The changes induced by middle-ear manipulations matched the predictions computed from a standard lumped-element middle-ear model, with one or two peaks around the resonance frequency(ies) of the involved subsystem, stapes or tympanic membrane. In contrast, the efferent effect was completely different, exhibiting a broadband-level suppression associated with a small phase lead. We propose that a careful vector analysis of otoacoustic emission modifications enables the identification of the contribution of the efferent reflex without ambiguity even when it is mixed with middle-ear effects. Thereby, otoacoustic emissions can be used more reliably as noninvasive probes of efferent olivocochlear function.     

Choline acetyltransferase activity in the hamster central auditory system and long‐term effects of intense tone exposure

Acoustic trauma often leads to loss of hearing of environmental sounds, tinnitus, in which a monotonous sound not actually present is heard, and/or hyperacusis, in which there is an abnormal sensitivity to sound. Research on hamsters has documented physiological effects of exposure to intense tones, including increased spontaneous neural activity in the dorsal cochlear nucleus. Such physiological changes should be accompanied by chemical changes, and those chemical changes associated with chronic effects should be present at long times after the intense sound exposure. Using a microdissection mapping procedure combined with a radiometric microassay, we have measured activities of choline acetyltransferase (ChAT), the enzyme responsible for synthesis of the neurotransmitter acetylcholine, in the cochlear nucleus, superior olive, inferior colliculus, and auditory cortex of hamsters 5 months after exposure to an intense tone compared with control hamsters of the same age. In control hamsters, ChAT activities in auditory regions were never more than one‐tenth of the ChAT activity in the facial nerve root, a bundle of myelinated cholinergic axons, in agreement with a modulatory rather than a dominant role of acetylcholine in hearing. Within auditory regions, relatively higher activities were found in granular regions of the cochlear nucleus, dorsal parts of the superior olive, and auditory cortex. In intense‐tone‐exposed hamsters, ChAT activities were significantly increased in the anteroventral cochlear nucleus granular region and the lateral superior olivary nucleus. This is consistent with some chronic upregulation of the cholinergic olivocochlear system influence on the cochlear nucleus after acoustic trauma. © 2013 Wiley Periodicals, Inc.     

Sympathectomy improves the ear's resistance to acoustic trauma – could stress render the ear more sensitive?

Emotional stress is a phenomenon experienced by many people at some time in their lives. Some of its early manifestations, such as unbearable loudness of ambient sounds and sensations of dizziness, might be linked to inner ear dysfunction. Although the inner ear is supplied with a substantial sympathetic innervation, previous studies have failed to demonstrate any significant functional impact. We show here that in the awake guinea pig and following unilateral ablation of the superior cervical ganglion, the temporary threshold shift induced by a 1-min exposure to 8 kHz pure tone at 96 dB sound pressure level was reduced by as much as 40 dB. Of interest, the protective effect was bilateral suggesting an intimate relationship between the sympathetic and the olivocochlear efferent systems. The data presented here provide new evidence for a key role for the sympathetic system in modulating temporary threshold shifts following exposure to moderate sound stimulation. This opens new perspectives for investigation of sympathetic control in noise-induced permanent hearing losses.     

Medial olivocochlear efferent activity in awake guinea pigs

Cochlear outer hair cells receive numerous connections from the medial olivocochlear efferent neurons. Medial olivocochlear efferent activity is highly dependent on the level of anesthesia. The present study was thus designed to investigate the efficiency of contralateral white noise stimulation on the distortion product otoacoustic emissions (DPOAEs) in a large number of awake guinea pigs, and to compare in the same animals the effect of urethane- and pentobarbitone-anesthesia. The monitoring of DPOAEs during contralateral white noise stimulation in awake animals requires the development of a soft restraining box, together with a conditioning technique for the animals to accept the contralateral sound and DPOAEs monitoring device. This technique allows us to demonstrate that contralateral sound suppression is much stronger in awake than in anesthetized animals. In all the cases, the contralateral sound suppression was abolished 3 h after i.m. injection of gentamicin, an aminoglycoside antibiotic which blocks the medial olivocochlear efferents. These results suggest that future studies have to explore the function of medial olivocochlear efferents in awake animals.     

Evidence of a medial olivocochlear involvement in contralateral suppression of otoacoustic emissions in humans

Otoacoustic emissions (OAEs) evoked by click stimuli were recorded in both ears of 20 normal human subjects, in the presence and absence of a contralateral masking broad band noise. No difference in the amplitude of OAE suppression was noted between the first tested ear and the second one. In addition, 20 pathological subjects were tested according to the same protocol. Ten of them belonged to a group of patients whose vestibular nerve was sectioned on one side to relieve incapacitating vertigo and thus represented a group in whom olivocochlear efferents were severed. A great reduction of suppression observed in the operated ear suggested that olivocochlear efferent fibers are necessary to obtain a full suppressive effect. Three of the pathological subjects were patients who had undergone a decompression of the facial nerve which necessitated the same surgical approach as vestibular neurotomy, but without any section of vestibular fibers. This surgical control group demonstrated that the surgical act by itself cannot explain the difference observed in the neurotomized group. Finally, seven of the pathological subjects were patients with Bell's palsy, which paralyses the facial nerve and abolishes the stapedial reflex. No suppression difference was observed between healthy ears and ears without stapedial reflex. Therefore, it appeared that the stapedial reflex was not involved in the contralateral suppression of EOAEs. However, as the tensor tympani muscle remained functional in these patients, its involvement in the suppressive effect cannot be excluded.     

Effects of heat stress on Young's modulus of outer hair cells in mice

Intense sound exposure causes permanent hearing loss due to hair cell and cochlear damage. Prior conditioning with sublethal stressors, such as nontraumatic sound, heat stress and restraint protects the ear from acoustic injury. However, the mechanisms underlying conditioning-related cochlear protection remain unknown. In this paper, Young's modulus and the amount of filamentous actin (F-actin) of outer hair cells (OHCs) with/without heat stress were investigated by atomic force microscopy and confocal laser scanning microscopy, respectively. Conditioning with heat stress resulted in a statistically significant increase in Young's modulus of OHCs at 3-6 h after application, and such modulus then began to decrease by 12 h and returned to pre-conditioning level at 48 h after heat stress. The amount of F-actin began to increase by 3 h after heat stress and peaked at 12 h. It then began to decrease by 24 h and returned to the pre-conditioning level by 48-96 h after heat stress. These time courses are consistent with a previous report in which heat stress was shown to suppress permanent threshold shift (PTS). In addition, distortion product otoacoustic emissions (DPOAEs) were confirmed to be enhanced by heat stress. These results suggest that conditioning with heat stress structurally modifies OHCs so that they become stiffer due to an increase in the amount of F-actin. As a consequence, OHCs possibly experience less strain when they are exposed to loud noise, resulting in protection of mammalian hearing from traumatic noise exposure.     

Inferior colliculus stimulation causes similar efferent effects on ipsilateral and contralateral cochlear potentials in the guinea pig

The inferior colliculus (IC) is a processing center in both the ascending and descending auditory pathways. It has been demonstrated anatomically to send descending projections to the region of the medial olivocochlear (MOC) neurons in the auditory brainstem. Activation of MOC system produces reductions in cochlear neural activity. Individual MOC fibers innervate relatively restricted regions of the cochlea. Recent studies have shown that selective electrical stimulation within the IC central nucleus (ICC) produces frequency-specific reductions of neural activity in the contralateral cochlea (Ota, Y., Oliver, D.L., Dolan, D.F., 2004. Frequency-specific effects on cochlear responses during activation of the inferior colliculus in the guinea pig. J. Neurophysiol. 91, 2185-2193). This efferent effect is likely mediated through selective activation of MOC cells. In this study, we investigated the effects of selective stimulation of one ICC on cochlear output in both ears in anesthetized and paralyzed guinea pigs to explore possible differences in the effective efferent innervation of the two ears. ICC stimulation had a similar tonotopically tuned effect on the distortion product otoacoustic emission (DPOAE) and the cochlear whole-nerve action potential (CAP) in each cochlea. The bandwidth of the efferent effect in each ear was measured and compared at different stimulation levels. For a given ICC stimulation site, the efferent effects were larger for the CAP response. The effect on each response measure was greater in the contralateral than the ipsilateral ear. The effective bandwidth of the efferent effect on the CAP was current-level-dependent but less so for the DPOAE. The results of transections at various locations within the brainstem suggest that the effects were mediated by the MOC system. From the results presented here, the descending efferent system, which originates in the auditory cortex, has frequency-specific, spatially restricted, bilateral effects. The effects are greater in the contralateral ear.     

The effect of monaural middle ear destruction on response properties of neurons in the auditory midbrain of juvenile and adult mice

This article reviews our studies of the effect of monaural middle ear destruction on midbrain auditory response properties of the laboratory mouse, Mus musculus. Monaural middle ear destruction was performed on juvenile and adult mice and the auditory sensitivity of neurons in the midbrain inferior colliculus (IC) ipsilateral and contralateral to the intact ear was examined 4 weeks later. When stimulated with sound pulses, IC neurons of the control mice typically had lower minimum threshold, larger dynamic range, and sharper frequency tuning curve than IC neurons of the experimental juvenile and adult mice. In the experimental mice, neurons in the ipsilateral IC had significantly longer latency, higher minimum threshold, and smaller dynamic range than neurons in the contralateral IC. When determined at two sound directions (ipsilateral 40 degrees and contralateral 40 degrees to the recording site), IC neurons of the control mice had higher minimum threshold, sharper frequency tuning curve but smaller dynamic range at I-40 degrees than at C-40 degrees . However, these direction-dependent response properties were not observed for IC neurons of the experimental juvenile and adult mice. Clear tonotopic organization was only observed in the IC of the control mice and experimental adult mice but not in the IC of experimental juvenile mice. These different response properties are discussed in relation to the effect of monaural middle ear destruction.     

Cochlear-nucleus branches of thick (medial) olivocochlear fibers in the mouse: a cochleotopic projection

Olivocochlear neurons have somata in the superior olivary complex and provide an efferent innervation to the cochlea. One subgroup of olivocochlear neurons, medial olivocochlear neurons, sends fibers to innervate the cochlear outer hair cells. En route to the cochlea, medial olivocochlear fibers give off branches to the ventral cochlear nucleus, the first auditory center of the brain. This study examines the cochlear-nucleus branches of medial olivocochlear fibers, comparing those from fibers that innervate the cochlear base with those from fibers that innervate the cochlear apex. Basal fibers give off dorsal branches to the granule cell lamina and ventral branches to the auditory nerve root. Apical fibers give off few dorsal branches but many ventral branches that terminate rostrally to the nerve root. This cochleotopic mapping of medial olivocochlear branches corresponds in a general way to that of afferent fibers. Unlike afferent fibers, however, the branches terminate primarily along the edges of the cochlear nucleus. In the mouse, the particular edges of termination are (1) the medial border of the ventral cochlear nucleus where it meets the underlying vestibular nerve root, and (2) the border between the ventral cochlear nucleus and the granule cell lamina. Neurons and dendrites of these border regions may thus integrate efferent and afferent information in a frequency-specific manner.     

Neuroprotective effect of riluzole in acute noise-induced hearing loss

Riluzole has been reported to protect against the deleterious effect of cerebral ischemia by blocking glutamatergic neurotransmission. Here, we investigated whether acoustic trauma-induced cochlear excitotoxicity could be attenuated by riluzole. Cumulative intracochlear perfusion of riluzole completely abolished single-nerve fiber activity in the guinea pig cochlea and the compound action potential of the auditory nerve. Guinea pigs treated with riluzole (100 microM) showed significantly less hearing threshold shift than untreated guinea pigs, and presented no sign of dendritic damage in the cochlea observable by electron microscopy. When coapplied with glutamate, riluzole did not prevent glutamate-induced swelling of auditory nerve dendrites, suggesting that the protective effect of riluzole was mediated principally by inhibition of glutamate release from sensory inner hair cells.     

Interaural attention modulates outer hair cell function

Mounting evidence suggests that auditory attention tasks may modulate the sensitivity of the cochlea by way of the corticofugal and the medial olivocochlear (MOC) efferent pathways. Here, we studied the extent to which a separate efferent tract, the ‘uncrossed’ MOC, which functionally connects the two ears, mediates inter‐aural selective attention. We compared distortion product otoacoustic emissions (DPOAEs) in one ear with binaurally presented primaries, using an intermodal target detection task in which participants were instructed to report the occurrence of brief target events (visual changes, tones). Three tasks were compared under identical physical stimulation: (i) report brief tones in the ear in which DPOAE responses were recorded; (ii) report brief tones presented to the contralateral, non‐recorded ear; and (iii) report brief phase shifts of a visual grating at fixation. Effects of attention were observed as parallel shifts in overall DPOAE contour level, with DPOAEs relatively higher in overall level when subjects ignored the auditory stimuli and attended to the visual stimulus, compared with both of the auditory‐attending conditions. Importantly, DPOAE levels were statistically lowest when attention was directed to the ipsilateral ear in which the DPOAE recordings were made. These data corroborate notions that top‐down mechanisms, via the corticofugal and medial efferent pathways, mediate cochlear responses during intermodal attention. New findings show attending to one ear can significantly alter the physiological response of the contralateral, unattended ear, probably through the uncrossed‐medial olivocochlear efferent fibers connecting the two ears.     

Short-term synaptic plasticity regulates the level of olivocochlear inhibition to auditory hair cells

In the mammalian inner ear, the gain control of auditory inputs is exerted by medial olivocochlear (MOC) neurons that innervate cochlear outer hair cells (OHCs). OHCs mechanically amplify the incoming sound waves by virtue of their electromotile properties while the MOC system reduces the gain of auditory inputs by inhibiting OHC function. How this process is orchestrated at the synaptic level remains unknown. In the present study, MOC firing was evoked by electrical stimulation in an isolated mouse cochlear preparation, while OHCs postsynaptic responses were monitored by whole-cell recordings. These recordings confirmed that electrically evoked IPSCs (eIPSCs) are mediated solely by α9α10 nAChRs functionally coupled to calcium-activated SK2 channels. Synaptic release occurred with low probability when MOC-OHC synapses were stimulated at 1 Hz. However, as the stimulation frequency was raised, the reliability of release increased due to presynaptic facilitation. In addition, the relatively slow decay of eIPSCs gave rise to temporal summation at stimulation frequencies >10 Hz. The combined effect of facilitation and summation resulted in a frequency-dependent increase in the average amplitude of inhibitory currents in OHCs. Thus, we have demonstrated that short-term plasticity is responsible for shaping MOC inhibition and, therefore, encodes the transfer function from efferent firing frequency to the gain of the cochlear amplifier.