Olivocochlear Bundle Research Articles

Auditory Efferent Pathway Functioning in Individuals with Misophonia

Background and Aim: Misophonia, characterized by a decreased tolerance for specific auditory stimuli, has been insufficiently explored within audiology. Limited research has been conducted, and the auditory mechanisms involved in this disorder remain to be explored. Hence, our study aimed to investigate the auditory efferent systems in individuals with misophonia. By focusing on this specific aspect, we aim to contribute to a better understanding of misophonia and shed light on the underlying auditory mechanisms involved in the condition. Methods: A cross-sectional research was performed with students from Mysore University to investigate misophonia. The severity of misophonia was evaluated using the revised Amsterdam misophonia scale. The participants were divided into two groups based on their misophonia severity: mild (n=15) and moderate-severe (n=15). All participants underwent transient evoked otoacoustic emissions with contralateral suppression to assess the auditory function. The overall amplitude and frequency-specific amplitudes were analyzed and compared across the various groups. Results: The analysis of variance results revealed no significant differences between the groups in global amplitude suppression and suppression of all frequencies. These findings imply that the medial-olivocochlear bundle efferent pathway is intact among individuals with misophonia. Conclusion: Our findings have concluded that the medial olivocochlear bundle appears intact among individuals with misophonia (p>0.05). However, it is essential to note that the generalizability of these findings may be limited due to the relatively small sample size used in our study. Therefore, further research involving a more extensive and diverse population is needed to validate and generalize these conclusions. Keywords: Misophonia; efferent pathway; contralateral suppression; neurophysiology; audiology

The role of the Ventral Nucleus of the Trapezoid Body in the auditory prepulse inhibition of the acoustic startle reflex

Cholinergic signaling is essential to mediate the auditory prepulse inhibition (PPI), an operational measure of sensorimotor gating, that refers to the reduction of the acoustic startle reflex (ASR) when a low-intensity, non-startling acoustic stimulus (the prepulse) is presented just before the onset of the acoustic startle stimulus. The cochlear root neurons (CRNs) are the first cells of the ASR circuit to receive cholinergic inputs from non-olivocochlear neurons of the ventral nucleus of the trapezoid body (VNTB) and subsequently decrease their neuronal activity in response to auditory prepulses. Yet, the contribution of the VNTB-CRNs pathway to the mediation of PPI has not been fully elucidated. In this study, we used the immunotoxin anti-choline acetyltransferase (ChAT)-saporin as well as electrolytic lesions of the medial olivocochlear bundle to selectively eliminate cholinergic VNTB neurons, and then assessed the ASR and PPI paradigms. Retrograde track-tracing experiments were conducted to precisely determine the site of lesioning VNTB neurons projecting to the CRNs. Additionally, the effects of VNTB lesions and the integrity of the auditory pathway were evaluated via auditory brain responses tests, ChAT- and FOS-immunohistochemistry. Consequently, we established three experimental groups: 1) intact control rats (non-lesioned), 2) rats with bilateral lesions of the olivocochlear bundle (OCB-lesioned), and 3) rats with bilateral immunolesions affecting both the olivocochlear bundle and the VNTB (OCB/VNTB-lesioned). All experimental groups underwent ASR and PPI tests at several interstimulus intervals before the lesion and 7, 14, and 21 days after it. Our results show that the ASR amplitude remained unaffected both before and after the lesion across all experimental groups, suggesting that the VNTB does not contribute to the ASR. The%PPI increased across the time points of evaluation in the control and OCB-lesioned groups but not in the OCB/VNTB-lesioned group. At the ISI of 50 ms, the OCB-lesioned group exhibited a significant increase in%PPI (p < 0.01), which did not occur in the OCB/VNTB-lesioned group. Therefore, the ablation of cholinergic non-olivocochlear neurons in the OCB/VNTB-lesioned group suggests that these neurons contribute to the mediation of auditory PPI at the 50 ms ISI through their cholinergic projections to CRNs. Our study strongly reinforces the notion that auditory PPI encompasses a complex mechanism of top-down cholinergic modulation, effectively attenuating the ASR across different interstimulus intervals within multiple pathways.

Measuring and modeling Gaussian noise disruption across frequency, level, and hearing status

Recent work suggested that older listeners with minimal hearing loss exhibit more forward masking for a highly fluctuating Gaussian noise (GN) masker relative to a low-fluctuation noise (LFN) masker. This threshold difference (GN–LFN) is referred to as GN disruption and was previously attributed to time-varying cochlear gain resulting from feedback control by the medial olivocochlear (MOC) system. However, thus far, masker conditions have been limited to 80 dB SPL at 4 kHz. The current study aims to challenge the hypothesis that the physiological basis of GN disruption is the MOC system using behavioral measures and computational models across multiple target and masker frequencies (0.5, 1, 2, and 4 kHz), masker levels (80-, 65-, and 50-dB SPL), masker-signal delays (25- and 75-ms), participant age ranges (18–30 and 60–75), and hearing statuses (normal hearing, sensorineural hearing loss). Additionally, speech recognition using IEEE sentences will be measured with GN and LFN maskers. Although testing will not be completed until 2025, preliminary data from 20 younger participants with normal hearing suggest that GN disruption is greater for higher than lower masker and probe frequencies, that GN disruption is similar across masker levels, and that refinements to the computational model are needed to more accurately predict GN disruption.

Contralateral Suppression of Acoustic Reflex in Individuals with Chronic Subjective Tinnitus

Objectives: The first aim of this study is to determine whether subjective tinnitus has an effect on the medial olivocochlear bundle function in the auditory efferent system, with the contralateral acoustic reflex suppression test. The second aim is to contribute to the literature on the auditory efferent system. Materıals and Methods: The study included 20 individuals with chronic subjective tinnitus and 28 healthy controls. Acoustic reflex measurement was applied to both groups at 0.5, 1, and 2 kHz with and without contralateral noise. The contralateral suppression of the acoustic reflex (CSAR) results of both groups were compared in terms of CSAR threshold (CSART) and CSAR amplitude (CSARA). Results: There was no significant difference between the control and tinnitus groups in terms of CSART (P &gt; 0.05), except that the left ear of the tinnitus group was higher than the control group at 0.5 kHz (P = 0.015). There was no significant difference in CSARA of the ears at all frequencies between the two groups (P &gt; 0.05). Conclusion: These results suggest that the CSAR test can be used as a complementary test in the evaluation of the auditory efferent system of individuals with chronic subjective tinnitus.

Speech Perception in Noise and Medial Olivocochlear Reflex: Effects of Age, Speech Stimulus, and Response-Related Variables.

The role of the medial olivocochlear system in speech perception in noise has been debated over the years, with studies showing mixed results. One possible reason for this could be the dependence of this relationship on the parameters used in assessing the speech perception ability (age, stimulus, and response-related variables). The current study assessed the influence of the type of speech stimuli (monosyllables, words, and sentences), the signal-to-noise ratio (+5, 0, -5, and -10dB), the metric used to quantify the speech perception ability (percent-correct, SNR-50, and slope of the psychometric function) and age (young vs old) on the relationship between medial olivocochlear reflex (quantified by contralateral inhibition of transient evoked otoacoustic emissions) and speech perception in noise. A linear mixed-effects model revealed no significant contributions of the medial olivocochlear reflex to speech perception in noise. The results suggest that there was no evidence of any modulatory influence of the indirectly measured medial olivocochlear reflex strength on speech perception in noise.

Effects of orienting attention to a specific frequency on medial olivocochlear reflex - A study of dependence on target frequencies -

The medial olivocochlear bundle responds to acoustic stimuli and suppresses outer hair cell gain. This reflex response is called the medial olivocochlear reflex (MOCR) and improves signal detection in background noise, referred to anti-masking effect. Our previous study reported that orienting attention to moderate frequencies selectively increases MOCR near the attended frequency, and that the effects of attention to low and high frequencies are unlikely to appear in MOCR. The previous investigation was limited to the condition where participants kept orienting attention to the same frequency across trials. Here we examined the condition where participants switched attention to different frequencies trial by trial. During the measurements of MOCR, participants detected probe tones in background noise. The target frequency, 750, 1000, 1250, 1500, 2000 and 3000 Hz, was notified by a preceding cue frequency and varied across trials. When the target frequency was 1250 Hz, the MOCR strength tended to be attenuated at lower frequencies. In contrast, for any other target frequencies, MOCR didn't differ significantly from a non-attentional condition. The frequency range where attentional effect was observed was similar to our previous report. The similarity implicates that MOCR can covary with dynamically changing frequency-specific attention, which would help exerting antimasking effect flexibly.

Olivocochlear efferent system degeneration and plasticity with aging and noise exposure

Contributions of the ascending peripheral and central auditory pathways to age-related and noise-induced hearing deficits have been well-characterized, but we know comparatively little about how the descending projections from the brain to the cochlea contribute to hearing deficits. Studies have shown dynamic structural and neurochemical changes in the olivocochlear system associated with acoustic experience and age, indicating that olivocochlear efferents cannot be considered a static system when attempting to reveal effects on hearing. I will summarize our efforts to understand how these pathways are involved in hearing dysfunction measured using physiological, behavioral, and anatomical assays in mouse models. Our work suggests that loss of olivocochlear efferent neurons is most detrimental to hearing in aged and aged, noise-exposed auditory systems which are already working with reduced afferent input to the brain. Furthermore, noise-induced changes in the lateral olivocochlear efferents appear to compensate for diminished medial olivocochlear activity—an effect that may explain the variable behavioral outcomes in hearing in noise studies involving the medial olivocochlear reflex in humans and animal models.

Evaluation of the auditory findings of patients with obstructive sleep apnea syndrome

ObjectivesTo investigate the effects of hypoxia occurring in patients with Obstructive Sleep Apnea Syndrome (OSAS) on Auditory evoked late latency, Auditory brainstem response, and the contralateral suppression of otoacoustic emissions. Materials and methods46 patients diagnosed with OSAS were divided into groups as moderate and severe based on their Apnea Hipopnea Index (AHI) values. The control group consisted of 22 healthy individuals. All participants underwent an Auditory Brainstem Response (ABR) test, Auditory Evoked Late Latency Response (LLR), and Contralateral Suppression Otoacoustic Emission (CS-OAE). FindingsThere was no statistical difference between the OSAS group and the control group regarding P1 latency, N1 latency, and P1 and N1 wave amplitude (p > 0.05). In ABR, statistically significant differences were found between the control, moderate OSAS, and severe OSAS groups in wave I in the right and left ear (p < 0.05). In the analyses performed for the otoacoustic emission frequencies with and without contralateral suppression of the right and left ear, suppression was not observed at some frequencies, and this was regarded as statistically significant (p < 0.05). ConclusionIt is considered that OSAS does not have cortical effects but impacts the brainstem region and the cochlea. Bilateral impact, especially observed in wave I of ABR, is prominent on the auditory nerve. Considering that the medial olivo-cochlear (MOC) system is affected in patients with OSAS, it is thought that these patients are inadequate in suppressing noise, and this may cause various problems, particularly the inability to distinguish speech in noisy environments.

Efferent Control in Musicians: A Review

It is widely established that musicians possess a higher level in certain auditory perceptual abilities when compared to non-musicians. This improvement may be mediated, at least in part, by changes in the cochlear response induced by reflex activation of the olivocochlear efferent system. In this review, we describe and analyze the scientific evidence regarding possible differences in the efferent response in musicians and non-musicians. The main evidence observed is that musicians present a greater robustness of the efferent olivocochlear reflex when measured by suppression of otoacoustic emissions and compared to non-musicians. Analyzing the articles presented in this review, it is possible to point out that the differential role of the efferent effect in musicians is not yet established. There is not enough evidence to support the idea that the olivocochlear system favors comparative changes in the properties of musicians' auditory filters. New studies with psychoacoustic techniques, among others, are needed to measure the effect of the olivocochlear reflex on tuning, gain, compression, or temporal resolution in musicians and non-musicians.

Easy and Hard Auditory Tasks Distinguished by Otoacoustic Emissions and Event-related Potentials: Insights into Efferent System Activity

The medial olivocochlear (MOC) system is thought to be responsible for modulation of peripheral hearing through descending (efferent) pathways. This study investigates the connection between peripheral hearing function and auditory attention tasks of different degrees of difficulty. Peripheral hearing function was evaluated by analyzing the amount of change in otoacoustic emissions (OAEs) by contralateral acoustic stimulation (CAS), a well-known effect of the MOC system. Simultaneously, levels of attention were evaluated by event-related potentials (ERPs). The ERPs showed clear differences in processing tasks of different difficulty, but paradoxically there was no difference in the amount of OAE change brought about by CAS. There was also no effect on OAE latency, nor was there any difference in noise level or number of rejected trials. However, we observed that the changes in OAEs by CAS for easy and hard tasks were correlated with the magnitude of the P3 wave in the ERP. This suggests there might be some sort of mutual compensation mechanism – presently unknown – between periphery and cortex.

Does SARS-CoV-2 affect cochlear functions in children?

Objectives:To determine the influence of coronavirus disease-19 (COVID-19) on cochlear tasks of children who had COVID-19 previously, and the relevance among disease seriousness and cochlear involvement by otoacoustic emissions (OAEs).Methods:The study included 24 hospitalized children after COVID-19 diagnosis, 23 pediatrics that received outpatient treatment, and 21 children who were without COVID-19 diagnosis as the control group between June 2021 and July 2021. Transient evoked otoacoustic emission (TEOAE), distortion product otoacoustic emission, and contrlateral suppression of otoacoustic emission measurements were carried out for each child. Symptoms of patients, the treatments they received, and the duration of hospitalization of the children in the hospitalized group were recorded.Results:The comparison of TEOAE test results under masking showed a considerable difference between 3 groups at 1 kHz (p=0.033) and 4 kHz (p=0.021) frequencies (p<0.05). Distortion product otoacoustic emission test results of hospitalized outpatient and control group showed a statistically significant difference at 2 kHz among themselves (p=0.009).Conclusion:Our results suggest that severe acute respiratory syndrome coronavirus-2 may influence the medial olivocochlear system of children and have irreversible effects on the cochlear functions. Early detection of problems that may affect cochlear functions is a special critical task, especially in children, who are a particularly vulnerable group in terms of hearing and related speech problems.

Evaluation of the Auditory System in Autistic Children Using Evoked Otoacoustic Emissions and a Contralateral Suppression Test.

In this study, we evaluated the cochlea, medial olivocochlear system, and brainstem function in autistic children using evoked otoacoustic emissions (OAEs) and a noninvasive contralateral suppression (CLS) test. In total, we included 21 autistic children with normal hearing (study group) and 11 healthy children (control group). Transient-evoked OAEs (TEOAEs) and CLS of TEOAE were evaluated in the left and right ears of all patients. In a silent room, spontaneous, transient, and dP ILO292 were evaluated. The mean age of the study and control group was 9.1 years (range: 6-13 and 6-12 years, respectively). For the study group, there was no statistically significant difference between the OAE and CLS values of the right ear (P > .05). However, for the left ears, OAE values were statistically significantly higher than the CLS values (P < .05). In the control group, the OAE values of both ears were statistically significantly higher than the CLS values (P < .05). In autistic children with normal hearing, the medial olivocochlear system functions more effectively in the right ear than the left ear. Asymmetry between the ears islikely responsible for the peripheral auditory lateralization and independence in auditory function between the left and rightears.

The Long and Winding Road-Vestibular Efferent Anatomy in Mice.

The precise functional role of the Efferent Vestibular System (EVS) is still unclear, but the auditory olivocochlear efferent system has served as a reasonable model on the effects of a cholinergic and peptidergic input on inner ear organs. However, it is important to appreciate the similarities and differences in the structure of the two efferent systems, especially within the same animal model. Here, we examine the anatomy of the mouse EVS, from its central origin in the Efferent Vestibular Nucleus (EVN) of the brainstem, to its peripheral terminations in the vestibular organs, and we compare these findings to known mouse olivocochlear anatomy. Using transgenic mouse lines and two different tracing strategies, we examine central and peripheral anatomical patterning, as well as the anatomical pathway of EVS axons as they leave the mouse brainstem. We separately tag the left and right efferent vestibular nuclei (EVN) using Cre-dependent, adeno-associated virus (AAV)-mediated expression of fluorescent reporters to map their central trajectory and their peripheral terminal fields. We couple this with Fluro-Gold retrograde labeling to quantify the proportion of ipsi- and contralaterally projecting cholinergic efferent neurons. As in some other mammals, the mouse EVN comprises one group of neurons located dorsal to the facial genu, close to the vestibular nuclei complex (VNC). There is an average of just 53 EVN neurons with rich dendritic arborizations towards the VNC. The majority of EVN neurons, 55%, project to the contralateral eighth nerve, crossing the midline rostral to the EVN, and 32% project to the ipsilateral eighth nerve. The vestibular organs, therefore, receive bilateral EVN innervation, but without the distinctive zonal innervation patterns suggested in gerbil. Similar to gerbil, however, our data also suggest that individual EVN neurons do not project bilaterally in mice. Taken together, these data provide a detailed map of EVN neurons from the brainstem to the periphery and strong anatomical support for a dominant contralateral efferent innervation in mammals.

The comprehensive audiological evaluation in young violinists: the medial olivocochlear system, high frequency thresholds, and the auditory figure ground test.

The aim of this study was to examine whether the medial olivocochlear hearing system functions, the high frequency hearing thresholds and speech discrimination in noise performance can guide us in assessing the risk of hearing loss among violinists. It is aimed to investigate possible hearing damage that is not reflected in pure tone hearing thresholds in violinists. The participants (n = 50) who have normal hearing and the ages of 18-30 were included in this study in two groups: violinists and controls who are unrelated to music. High frequency audiometer, auditory figure ground test (AFG) for speech discrimination in noise performance, Distortion Product Otoacoustic Emission (DPOAE) and contralateral suppression on DPOAE for medial olivocochlear system function tests were applied to all participants as well as routine audiological tests. The high frequency hearing thresholds were obtained higher in violinists compared to the controls. In violinists, the AFG test scores and the suppression amount at 1kHz were lower than the controls. In addition, DPOAE responses at 4-6kHz were obtained lower in violinists (p < 0.05). The reason for high frequency hearing loss, decreased DPOAE response amplitudes, and poor medial olivocochlear function in violinists can be explained by the long-term exposure to high-level noise caused by the violin, one of the closest musical instruments. Routine and comprehensive audiological follow-up is crucial for musicians.

Olivocochlear Changes Associated With Aging Predominantly Affect the Medial Olivocochlear System.

Age-related hearing loss (ARHL) is a public health problem that has been associated with negative health outcomes ranging from increased frailty to an elevated risk of developing dementia. Significant gaps remain in our knowledge of the underlying central neural mechanisms, especially those related to the efferent auditory pathways. Thus, the aim of this study was to quantify and compare age-related alterations in the cholinergic olivocochlear efferent auditory neurons. We assessed, in young-adult and aged CBA mice, the number of cholinergic olivocochlear neurons, auditory brainstem response (ABR) thresholds in silence and in presence of background noise, and the expression of excitatory and inhibitory proteins in the ventral nucleus of the trapezoid body (VNTB) and in the lateral superior olive (LSO). In association with aging, we found a significant decrease in the number of medial olivocochlear (MOC) cholinergic neurons together with changes in the ratio of excitatory and inhibitory proteins in the VNTB. Furthermore, in old mice we identified a correlation between the number of MOC neurons and ABR thresholds in the presence of background noise. In contrast, the alterations observed in the lateral olivocochlear (LOC) system were less significant. The decrease in the number of LOC cells associated with aging was 2.7-fold lower than in MOC and in the absence of changes in the expression of excitatory and inhibitory proteins in the LSO. These differences suggest that aging alters the medial and lateral olivocochlear efferent pathways in a differential manner and that the changes observed may account for some of the symptoms seen in ARHL.

Effects of Multisession Anodal Electrical Stimulation of the Auditory Cortex on Temporary Noise-Induced Hearing Loss in the Rat.

The protective effect of the efferent system against acoustic trauma (AT) has been shown by several experimental approaches, including damage to one ear, sectioning of the olivocochlear bundle (OCB) in the floor of the IV ventricle, and knock-in mice overexpressing outer hair cell (OHC) cholinergic receptors, among others. Such effects have been related to changes in the regulation of the cholinergic efferent system and in cochlear amplification, which ultimately reverse upon protective hearing suppression. In addition to well-known circuits of the brainstem, the descending corticofugal pathway also regulates efferent neurons of the olivary complex. In this study, we applied our recently developed experimental paradigm of multiple sessions of electrical stimulation (ES) to activate the efferent system in combination with noise overstimulation. ABR thresholds increased 1 and 2 days after AT (8–16 kHz bandpass noise at 107 dB for 90 min) recovering at AT + 14 days. However, after multiple sessions of epidural anodal stimulation, no changes in thresholds were observed following AT. Although an inflammatory response was also observed 1 day after AT in both groups, the counts of reactive macrophages in both experimental conditions suggest decreased inflammation in the epidural stimulation group. Quantitative immunocytochemistry for choline acetyltransferase (ChAT) showed a significant decrease in the size and optical density of the efferent terminals 1 day after AT and a rebound at 14 days, suggesting depletion of the terminals followed by a long-term compensatory response. Such a synthesis recovery was significantly higher upon cortical stimulation. No significant correlation was found between ChAT optical density and size of the buttons in sham controls (SC) and ES/AT + 1day animals; however, significant negative correlations were shown in all other experimental conditions. Therefore, our comparative analysis suggests that cochleotopic cholinergic neurotransmission is also better preserved after multisession epidural stimulation.

Medial Olivocochlear Functioning and Speech Perception in Noise in Individuals with Polycystic Ovary Syndrome

Introduction The current study aimed to evaluate the olivocochlear bundle functioning and speech perception in the presence of noise in females with Polycystic ovary syndrome (PCOS). Method Twenty participants in the age range of 18-25 years were included in the study. They were equally divided into two groups: group 1 included females diagnosed with PCOS, and group 2 included healthy adult male participants. Medial olivocochlear (MOC) functioning was evaluated using contralateral suppression of transient otoacoustic emissions (TEOAE). In addition, speech perception in noise was assessed using a quick speech perception in noise test in Malayalam. Results Results showed a significant difference for the TEOAE amplitude and signal to noise ratio (SNR) of TEOAEs in quiet and in the presence of contralateral noise and the speech perception in noise between the two groups. Also, no contralateral suppression was noted in the clinical group suggesting that MOC functioning is affected in individuals with PCOS. Conclusion It can be concluded that medial olivocochlear bundle functioning and speech perception in noise is affected in individuals with PCOS, which can be attributed to the abnormality in the hormonal status of PCOS.

The role of the medial olivocochlear reflex in psychophysical masking and intensity resolution in humans: a review.

This review addresses the putative role of the medial olivocochlear (MOC) reflex in psychophysical masking and intensity resolution in humans. A framework for interpreting psychophysical results in terms of the expected influence of the MOC reflex is introduced. This framework is used to review the effects of a precursor or contralateral acoustic stimulation on 1) simultaneous masking of brief tones, 2) behavioral estimates of cochlear gain and frequency resolution in forward masking, 3) the buildup and decay of forward masking, and 4) measures of intensity resolution. Support, or lack thereof, for a role of the MOC reflex in psychophysical perception is discussed in terms of studies on estimates of MOC strength from otoacoustic emissions and the effects of resection of the olivocochlear bundle in patients with vestibular neurectomy. Novel, innovative approaches are needed to resolve the dissatisfying conclusion that current results are unable to definitively confirm or refute the role of the MOC reflex in masking and intensity resolution.

Efferent feedback controls bilateral auditory spontaneous activity

In the developing auditory system, spontaneous activity generated in the cochleae propagates into the central nervous system to promote circuit formation. The effects of peripheral firing patterns on spontaneous activity in the central auditory system are not well understood. Here, we describe wide-spread bilateral coupling of spontaneous activity that coincides with the period of transient efferent modulation of inner hair cells from the brainstem medial olivocochlear system. Knocking out α9/α10 nicotinic acetylcholine receptors, a requisite part of the efferent pathway, profoundly reduces bilateral correlations. Pharmacological and chemogenetic experiments confirm that the efferent system is necessary for normal bilateral coupling. Moreover, auditory sensitivity at hearing onset is reduced in the absence of pre-hearing efferent modulation. Together, these results demonstrate how afferent and efferent pathways collectively shape spontaneous activity patterns and reveal the important role of efferents in coordinating bilateral spontaneous activity and the emergence of functional responses during the prehearing period.

Overexpression of Isl1 under the Pax2 Promoter, Leads to Impaired Sound Processing and Increased Inhibition in the Inferior Colliculus

The LIM homeodomain transcription factor ISL1 is essential for the different aspects of neuronal development and maintenance. In order to study the role of ISL1 in the auditory system, we generated a transgenic mouse (Tg) expressing Isl1 under the Pax2 promoter control. We previously reported a progressive age-related decline in hearing and abnormalities in the inner ear, medial olivocochlear system, and auditory midbrain of these Tg mice. In this study, we investigated how Isl1 overexpression affects sound processing by the neurons of the inferior colliculus (IC). We recorded extracellular neuronal activity and analyzed the responses of IC neurons to broadband noise, clicks, pure tones, two-tone stimulation and frequency-modulated sounds. We found that Tg animals showed a higher inhibition as displayed by two-tone stimulation; they exhibited a wider dynamic range, lower spontaneous firing rate, longer first spike latency and, in the processing of frequency modulated sounds, showed a prevalence of high-frequency inhibition. Functional changes were accompanied by a decreased number of calretinin and parvalbumin positive neurons, and an increased expression of vesicular GABA/glycine transporter and calbindin in the IC of Tg mice, compared to wild type animals. The results further characterize abnormal sound processing in the IC of Tg mice and demonstrate that major changes occur on the side of inhibition.