ABR/DPOAE publications

The striatum is the primary input nucleus of the basal ganglia, integrating a dense plexus of inputs from the cerebral cortex and thalamus to regulate action selection and learning. Neuroanatomical mapping of the striatum and its subcompartments has been carried out extensively in rats and mice, nonhuman primates, and cats allowing comparative neuroanatomy studies to derive heuristics about striatal composition and function. Here, we systematically map corticostriatal topography from motor, somatosensory, auditory, and visual cortices as well as thalamostriatal parafascicular (PfN) inputs in the Mongolian gerbil. We also map a pathway reported in mice from medial vestibular nucleus to the PfN that could convey vestibular information to the striatum. Our findings align with those of similar studies in other rodents, indicating homologous neuroanatomical connectivity patterns within the corticostriatal projectome across Rodentia. We observed corticostriatal peaks of dense labeling for each input with a diffuse projection throughout striatal subregions from each cortical region, suggesting a global integration of all cortical information by the striatum. Thalamostriatal projections from PfN covered most of the striatum with a peak of PfN-specific compartmentalized labeling similar to other sensory and motor systems. We also confirm the connection from the medial vestibular nucleus to PfN thalamus, indicating that vestibular information may be widely integrated throughout the striatum. The findings build upon our body of knowledge on striatal connectivity across mammalian species and provide a foundation for striatal research focusing on vestibulothalamostriatal circuits in Rodentia.

Kölliker's organ is a transient developmental structure in the mouse cochlea that undergoes significant remodeling postnatally. Utilizing an epithelial-specific conditional deletion mouse model of Prdm16 (marker and regulator of Kölliker's organ), we show that Prdm16 is required for interdental cell development, and thereby the development of the limbal domain of the tectorial membrane and its medial anchorage to the spiral limbus. Additionally, we show that Kölliker's organ is involved in normal tectorial membrane collagen fibril development and maturation. Interestingly, mesenchymal cells of the spiral limbus underneath Prdm16 -deficient Kölliker's organ failed to produce interstitial matrix proteins, resulting in a hypoplastic and truncated spiral limbus, indicating a non-cell autonomous role of Prdm16 in regulating spiral mesenchymal matrix development. Single-cell RNA sequencing identified differentially expressed genes in Prdm16 -deficient Kölliker's organ suggesting a role for connective tissue growth factor (CTGF) downstream Prdm16 in epithelial-mesenchymal signaling involved in spiral limbus matrix deposition. Prdm16 -deficient mice showed a hearing deficit, as indicated by elevated auditory brainstem response thresholds at most frequencies, consistent with the cochlear structural defects. Both sexes were studied. This work establishes Prdm16 as a deafness gene in mice through its role in regulating Kölliker's organ development. Such understanding recognizes Kölliker's organ as a developmental hub regulating multiple surrounding cochlear structures.

AMPA-type glutamate receptors (AMPARs) mediate excitatory cochlear transmission. However, unique roles of AMPAR subunits are unresolved. Lack of subunit GluA3 (Gria3 KO ) in male mice reduced cochlear output by 8 postnatal weeks. Here, we studied the role of X-linked Gria3 in cochlear function and synapse anatomy in females. Auditory brainstem responses (ABRs) were similar in 3-week-old female Gria3 WT and Gria3 KO mice raised in quiet. However, after switching to ambient sound, ABR thresholds were elevated and wave-1 amplitudes were diminished at 5-week and older in Gria3 KO . A quiet vivarium precluded this effect. Paired synapses were similar in number, but lone ribbons and ribbonless synapses were more frequent, and swollen afferent terminals were observed only in female Gria3 KO mice in ambient sound. Synaptic GluA4:GluA2 ratios increased relative to Gria3 WT , particularly in ambient sound, suggesting an activity-dependent increase in calcium-permeable AMPARs in Gria3 KO . We propose that lack of GluA3 induces a sex-dependent vulnerability to AMPAR-mediated excitotoxicity.

Age-related hearing loss (ARHL) is a complex condition with genetic, aging, and environmental influences. Sirtuins, particularly SIRT1, are NAD-dependent protein deacetylases critical to aging and stress responses. SIRT1 is modulated by nicotinamide N-methyltransferase (NNMT) and its product, N 1 -methylnicotinamide (MNAM), which influence ARHL progression. While SIRT1 is protective under certain conditions, its overexpression may paradoxically exacerbate hearing loss. This study examines MNAM supplementation’s impact on SIRT1 expression and ARHL in low-fat diet (LFD)-fed B6 and CBA mice. Mice were divided into LFD and LFD + MNAM groups and evaluated for auditory function, cochlear morphology, metabolic profiles, and SIRT1 expression at 3, 6, and 12 months of age. MNAM supplementation accelerated ARHL in both strains, with B6 mice showing more pronounced and earlier disease progression. Auditory brainstem response (ABR) thresholds were significantly elevated, and distortion-product otoacoustic emissions (DPOAE) indicated outer hair cell dysfunction. Cochlear histology revealed reduced hair cell and spiral ganglion cell counts, as well as decreased Na + /K + -ATPase α1 expression and endocochlear potential. MNAM increased SIRT1 protein levels in the cochlea without altering Sirt1 mRNA, suggesting post-transcriptional regulation. Metabolomic analysis revealed disrupted mitochondrial and oxidative pathways, including fatty acid oxidation and gluconeogenesis. Tricarboxylic acid (TCA) cycle dysregulation was evident, particularly in B6 mice, with elevated pyruvate, fumarate, and lactate levels. Despite similar metabolic trends in CBA mice, their slower aging profiles mitigated ARHL progression. These results suggest that while moderate SIRT1 expression protects against ARHL, overexpression disrupts metabolic homeostasis, accelerating cochlear aging and dysfunction. The dual role of SIRT1 emphasizes the need for precise modulation of its expression for effective therapeutic interventions. Future research should explore mechanisms underlying SIRT1-induced cochlear damage and strategies to maintain balanced SIRT1 expression. This study highlights MNAM’s detrimental effects on ARHL, underscoring its significance for developing targeted approaches to delay ARHL onset and preserve auditory function.

Assembly of actin-based stereocilia is critical for cochlear hair cells to detect sound. To tune their mechanosensivity, stereocilia form bundles composed of graded rows of ascending height, necessitating the precise control of actin polymerization. Myosin 15 (MYO15A) drives hair bundle development by delivering critical proteins to growing stereocilia that regulate actin polymerization via an unknown mechanism. Here, we show that MYO15A is itself an actin nucleation-promoting factor. Moreover, a deafness-causing mutation in the MYO15A actin-binding interface inhibits nucleation activity but still preserves some movement on filaments in vitro and partial trafficking on stereocilia in vivo. Stereocilia fail to elongate correctly in this mutant mouse, providing evidence that MYO15A-driven actin nucleation contributes to hair bundle biogenesis. Our work shows that in addition to generating force and motility, the ATPase domain of MYO15A can directly regulate actin polymerization and that disrupting this activity can promote cytoskeletal disease, such as hearing loss.

Loud noise exposure is one of the leading causes of permanent hearing loss. Individuals with noise-induced hearing loss (NIHL) suffer from speech comprehension deficits and experience impairments to cognitive functions such as attention and decision-making. Here, we investigate the specific underlying cognitive processes during auditory perceptual decision-making that are impacted by NIHL. Gerbils were trained to perform an auditory decision-making task that involves discriminating between slow and fast presentation rates of amplitude-modulated (AM) noise. Decision-making task performance was assessed across pre- versus post-NIHL sessions within the same gerbils. A single exposure session (2 h) to loud broadband noise (120 dB SPL) produced permanent NIHL with elevated threshold shifts in auditory brainstem responses (ABRs). Following NIHL, decision-making task performance was tested at sensation levels comparable to those prior to noise exposure in all animals. Our findings demonstrate NIHL diminished perceptual acuity, reduced attentional focus, altered choice bias, and slowed down evidence accumulation speed. Finally, video-tracking analysis of motor behavior during task performance demonstrates that NIHL can impact sensory-guided decision-based motor execution. Together, these results suggest that NIHL impairs the sensory, cognitive, and motor factors that support auditory decision-making.

Introduction Cisplatin is extensively employed in the treatment of multiple solid malignant tumors. Nevertheless, side effects such as cisplatin-induced ototoxicity (CIO) pose obstacles to tumor therapy.The important natural product chiisanoside from Acanthopanax sessiliflorus has abundant activity against CIO. Methods In this study, 26 chiisanoside derivatives were screened, and compound 19 demonstrated significant protective activity against CIO damage. A cisplatin—induced HEI—OC1 cell injury model and a mouse ototoxicity model were established. The regulatory effects were revealed through transcriptome sequencing, and the protein expression levels were analyzed by molecular docking, ELISA, Western blotting, and immunofluorescence. Results It was found that compound 19 inhibited cell apoptosis, alleviated abnormal hearing and spiral ganglion damage. Transcriptome sequencing revealed its regulatory effects. Compound 19 treatment increased autophagy levels, thereby alleviating mitochondrial dysfunction and reducing the accumulation of reactive oxygen species (ROS).In-depth studies have found that the autophagy inhibitor 3-methyladenine (3-MA) weakens the regulatory effect of compound 19 on autophagy and inhibits the clearance of damaged cells, resulting in oxidative stress damage, apoptosis and necrosis. By knocking down LRP6, it was found that the protective effect of compound 19 was eliminated, the autophagy level was significantly reduced, oxidative stress and ROS production were induced, and apoptosis after cisplatin exposure was promoted. Finally, the inhibitor LiCl was used to suppress the expression of GSK3β. It was found that inhibiting GSK3β could protect cells from cisplatin-induced damage by activating autophagy. Discussion These findings suggest that compound 19 is capable of preventing ototoxicity by activating autophagy via the LRP6/GSK3β axis and consequently inhibiting oxidative stress, offering a new approach for treating CIO and sensorineural hearing loss.

Noise-induced hearing loss is one of the most common forms of hearing loss in adults and also one of the most common occupational diseases. Extensive previous work has shown that the highly sensitive synapses of the inner hair cells (IHCs) may be the first target for irreparable damage and permanent loss in the noise-exposed cochlea, more precisely in the cochlear base. However, how such synaptic loss affects the synaptic physiology of the IHCs in this particularly vulnerable part of the cochlea has not yet been investigated. To address this question, we exposed 3–4-week-old C57BL/6J mice to 8–16 kHz noise for 2 h under isoflurane anesthesia. We then employed hearing measurements, immunohistochemistry and patch-clamp to assess IHC synaptic function. Two noise sound pressure levels (SPLs) were used to evoke acute hearing threshold elevations with different levels of recovery 2 weeks post-exposure. Regardless of noise intensity, the exposure resulted in a loss of approximately 25–36% of ribbon synapses in the basal portions of the cochlea that persisted 2 weeks after exposure. Perforated patch-clamp recordings were made in the IHCs of the basal regions of the cochlea where the greatest synaptic losses were observed. Depolarization-evoked calcium currents in IHCs 2 weeks after exposure were slightly but not significantly smaller as compared to controls from age-matched non-exposed animals. Exocytic changes monitored as changes in membrane capacitance did not follow that trend and remained similar to controls despite significant loss of ribbons, likely reflecting increased exocytosis at the remaining synapses. Additionally, we report for the first time that acute application of isoflurane reduces IHC calcium currents, which may have implications for noise-induced IHC synaptic loss.

Noise exposure is one of the most common causes of hearing loss and hyperacusis. Studies have shown that noise exposure can induce a cortical gain to compensate for reduced input of the cochlea, which may contribute to the increased sound sensitivity. However, many people with hyperacusis have no measurable cochlear lesion after being exposed to loud sound. In this experiment, we studied the neurological alterations in the cortical and subcortical areas following a prolonged moderate level of noise exposure (84 dB SPL, 8 h/day for 4 weeks) in the laboratory mice. The cochlear function was monitored by auditory brainstem responses (ABRs). The behavioral auditory sensitivity and temporal processing were evaluated using the acoustic startle response (ASR) and gap‐induced prepulse inhibition (gap‐PPI). The central auditory functions were determined by electrophysiological recordings of the inferior colliculus (IC) and the auditory cortex (AC). Our results showed that although there was no significant difference in the ABR thresholds, the noise group showed enhanced ASR and gap‐PPI compared to the control group. Increased neural activity in both the IC and the AC was recorded in the noise‐exposed mice compared to the control group, suggesting a central gain in both the subcortical and cortical regions. The current source density (CSD) analysis of the AC response revealed an increased columnar excitation and reduced corticocortical projection in the noise group, different from the central gain model of noise‐induced hearing loss. Our results suggest that chronic “nondestructive” noise can increase the gain of the central auditory system by altering the balance of auditory thalamocortical and intracortical inputs, which may contribute to the increased sound sensitivity in people with normal hearing.

Mutations in the human genes encoding the endothelin ligand-receptor pair EDN3 and EDNRB cause Waardenburg-Shah syndrome (WS4), which includes congenital hearing impairment. The current explanation for auditory dysfunction is defective migration of neural crest-derived melanocytes to the inner ear. We explored the role of endothelin signaling in auditory development in mice using neural crest-specific and placode-specific Ednrb mutation plus related genetic resources. On an outbred strain background, we find a normal representation of melanocytes in hearing-impaired mutant mice. Instead, our results in neural crest-specific Ednrb mutants implicate a previously unrecognized role for glial support of synapse assembly between auditory neurons and cochlear hair cells. Placode-specific Ednrb mutation also caused impaired hearing, resulting from deficient synaptic transmission. Our observations demonstrate the significant influence of genetic modifiers in auditory development, and invoke independent and separable roles for endothelin signaling in the neural crest and placode lineages to create a functional auditory circuitry.

GJB2 encodes connexin 26 (Cx26), the most commonly mutated gene causing hereditary non‐syndromic hearing loss. Cx26 is mainly expressed in supporting cells (SCs) and fibrocytes in the mammalian cochlea. Gene therapy is currently considered the most promising strategy for eradicating genetic diseases. However, there have been no significant effects of gene therapy for GJB2 gene mutation‐associated deafness because deficiency of Cx26 leads to expanded sensory epithelial damage. In this study, the AAV2.7m8 serotype combined with the gfaABC1D promoter targeted infection of SCs is identified. It is found that Gjb2 gene replacement therapy in wild‐type mice results in sensory hair cells (HCs) deficits, excessive inflammatory responses, and hearing loss. This may be one of the key factors contributing to the hardship of GJB2 gene replacement therapy. Dexamethasone (DEX) shows promising results in inhibiting macrophage recruitment, with a protective effect against HC damage. Further, the combination of AAV2.7m8‐ Gjb2 with DEX shows a synergistic effect and enhances the gene therapy effect in a conditional Cx26 null mice model. These results indicate that the combination of gene therapy and medication will provide a new strategy for the treatment of hereditary deafness associated with GJB2 defects.

To encode continuous sound stimuli, the inner hair cell (IHC) ribbon synapses utilize calcium-binding proteins (CaBPs), which reduce the inactivation of their Ca V 1.3 calcium channels. Mutations in the CABP2 gene underlie non-syndromic autosomal recessive hearing loss DFNB93. Besides CaBP2, the structurally related CaBP1 is highly abundant in the IHCs. Here, we investigated how the two CaBPs cooperatively regulate IHC synaptic function. In Cabp1/2 double-knockout mice, we find strongly enhanced Ca V 1.3 inactivation, slowed recovery from inactivation and impaired sustained exocytosis. Already mild IHC activation further reduces the availability of channels to trigger synaptic transmission and may effectively silence synapses. Spontaneous and sound-evoked responses of spiral ganglion neurons in vivo are strikingly reduced and strongly depend on stimulation rates. Transgenic expression of CaBP2 leads to substantial recovery of IHC synaptic function and hearing sensitivity. We conclude that CaBP1 and 2 act together to suppress voltage- and calcium-dependent inactivation of IHC Ca V 1.3 channels in order to support sufficient rate of exocytosis and enable fast, temporally precise and indefatigable sound encoding.

In the mammalian cochlea, sensory hair cells are crucial for the transduction of acoustic stimuli into electrical signals, which are then relayed to the central auditory pathway via spiral ganglion neuron (SGN) afferent dendrites. The SGN output is directly modulated by inhibitory cholinergic axodendritic synapses from the efferent fibers originating in the superior olivary complex. When the adult cochlea is subjected to noxious stimuli or aging, the efferent system undergoes major rewiring, such that it reestablishes direct axosomatic contacts with the inner hair cells (IHCs), which occur only transiently during prehearing stages of development. The trigger, origin, and degree of efferent plasticity in the cochlea remains largely unknown. Using functional and morphological approaches, we demonstrate that efferent plasticity in the adult cochlea occurs as a direct consequence of mechanoelectrical transducer current dysfunction. We also show that, different from prehearing stages of development, the lateral olivocochlear — but not the medial olivocochlear — efferent fibers are those that form the axosomatic synapses with the IHCs. The study also demonstrates that in vivo restoration of IHC function using AAV- Myo7a rescue reestablishes the synaptic profile of adult IHCs and improves hearing, highlighting the potential of using gene-replacement therapy for progressive hearing loss.

Current tests of hearing fail to diagnose pathologies in ~10% of patients seeking help for hearing difficulties. Neural ensemble responses to perceptually relevant cues in the amplitude envelope, termed envelope following responses (EFR), hold promise as an objective diagnostic tool to probe these 'hidden' hearing difficulties. But clinical translation is impeded by current measurement approaches involving static amplitude modulated (AM) tones, which are time-consuming and lack optimal spectrotemporal resolution. Here we develop a framework to rapidly measure EFRs using dynamically varying AMs combined with spectrally specific analyses. These analyses offer 5x improvement in time and 30x improvement in spectrotemporal resolution, and more generally, are optimal for analyzing time-varying signals with known spectral trajectories of interest. We validate this approach across several mammalian species, including humans, and demonstrate robust responses that are highly correlated with traditional static EFRs. Our analytic technique facilitates rapid and objective neural assessment of temporal processing throughout the brain that can be applied to track auditory neurodegeneration using EFRs, as well as tracking recovery after therapeutic interventions.

Pairing vagus nerve stimulation (VNS) with sounds has improved auditory processing in the auditory cortex of normal-hearing rats and autism models of rats. This study tests the ability of VNS-sound pairing to restore auditory processing in the inferior colliculus (IC) of valproic acid (VPA)-exposed rats. Pairing VNS with tones significantly reversed the degraded sound processing in the IC in VPA-exposed rats. The findings provide evidence that auditory processing in autism rat models can be improved through VNS.

Hearing mediates many behaviours critical for survival in echolocating bats, including foraging and navigation. Although most mammals are susceptible to progressive age-related hearing loss, the evolution of biosonar, which requires the ability to hear low-intensity echoes from outgoing sonar signals, may have selected against the development of hearing deficits in bats. Many echolocating bats exhibit exceptional longevity and rely on acoustic behaviours for survival to old age; however, relatively little is known about the ageing bat auditory system. In this study, we used DNA methylation to estimate the ages of wild-caught big brown bats ( Eptesicus fuscus ) and measured hearing sensitivity in young and ageing bats using auditory brainstem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs). We found no evidence for hearing deficits in bats up to 12.5 years of age, demonstrated by comparable thresholds and similar ABR and DPOAE amplitudes across age groups. We additionally found no significant histological evidence for cochlear ageing, with similar hair cell counts, afferent and efferent innervation patterns in young and ageing bats. Here, we demonstrate that big brown bats show minimal evidence for age-related hearing loss and therefore represent informative models for investigating mechanisms that may preserve hearing function over a long lifetime.

Myh1 is a mouse deafness gene with an unknown function in the auditory system. Hearing loss in Myh1 -knockout mice is characterized by an elevated threshold for the auditory brainstem response and the absence of a threshold for distortion product otoacoustic emission. Here, we investigated the role of MYH1 in outer hair cells (OHCs), crucial structures in the organ of Corti responsible for regulating cochlear amplification. Direct whole-cell voltage-clamp recordings of OHCs revealed that prestin activity was lower in Myh1 -knockout mice than in wild-type mice, indicating abnormal OHC electromotility. We analyzed whole-exome sequencing data from 437 patients with hearing loss of unknown genetic causes and identified biallelic missense variants of MYH1 in five unrelated families. Hearing loss in individuals harboring biallelic MYH1 variants was non-progressive, with an onset ranging from congenital to childhood. Three of five individuals with MYH1 variants displayed osteopenia. Structural prediction by AlphaFold2 followed by molecular dynamic simulations revealed that the identified variants presented structural abnormalities compared with wild-type MYH1. In a heterogeneous overexpression system, MYH1 variants, particularly those in the head domain, abolished MYH1 functions, such as by increasing prestin activity and modulating the membrane traction force. Overall, our findings suggest an essential function of MYH1 in OHCs, as observed in Myh1-deficient mice, and provide genetic evidence linking biallelic MYH1 variants to autosomal recessive hearing loss in humans.

The cochlea contains two extracellular fluids, perilymph and endolymph. Endolymph exhibits high potential of approximately +80 to +110 mV (depending on species), which sensitizes sensory hair cells. Other properties of this unique fluid remain elusive, owing to its minuscule volume in rodent cochlea. We therefore developed a technique to collect high-purity endolymph from mouse cochleae. Comprehensive proteomic analysis of sampled endolymph using liquid chromatography with mass spectrometry identified 301 proteins, dominated by molecules engaged in immunity and proteostasis. Approximately 30% of these proteins were undetectable in our perilymph. A combination of mass spectrometry and different approaches revealed that, compared to perilymph, endolymph was enriched with α2-macroglobulin, osteopontin, apolipoprotein D, apolipoprotein E, and apolipoprotein J/clusterin. In other cells or tissues, α2-macroglobulin, apolipoprotein E, and apolipoprotein J contribute to the clearance of degraded proteins from extracellular fluid. Altogether, with the proteins described here, endolymph may play a protective role in stabilizing cochlear homeostasis.

Cochlear ribbon synapses between sensory inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are vulnerable to rapid and primary damage and/or loss due to noise overexposure. Such damaged ribbon synapses can repair spontaneously in mouse and guinea pig. However, the mechanisms for synaptic repair are unclear. Previously, we have demonstrated a critical role for the fractalkine signaling axis (CX 3 CL1-CX 3 CR1) in synaptic repair, wherein noise-damaged ribbon synapses are spontaneously repaired in the presence of fractalkine receptor (CX 3 CR1) expressed by cochlear macrophages. Here, we examined whether local administration of chemokine fractalkine ligand (CX 3 CL1 or FKN) in the form of a peptide is effective in restoring synapses and hearing loss after noise-induced cochlear synaptopathy (NICS). Specifically, the efficacy of different isoforms of FKN was evaluated for restoration of loss of IHC ribbon synapses and hearing after NICS. A single transtympanic injection of soluble isoform of FKN (sFKN) peptide at 1 day after synaptopathic noise trauma for 2 hours at 93 decibel sound pressure level led to significant recovery of auditory brainstem response (ABR) thresholds, ABR peak I amplitudes and ribbon synapses in FKN knockout mice when compared to mice injected with membrane-bound FKN peptide (mFKN). Likewise, local treatment with sFKN peptide in FKN wild type mice restored synaptopathic noise-damaged ribbon synapses and ABR peak I amplitudes. Mechanistically, FKN regulates macrophage numbers in the damaged cochlea and in the absence of macrophages, sFKN failed to restore loss of synapses and hearing after NICS. Furthermore, sFKN treatment attenuated cochlear inflammation after NICS without altering the expression of CX 3 CR1. Finally, injected sFKN peptide was detectable inside the cochlea for 24 h localized to the basilar membrane and spiral lamina near the sensory epithelium. These data provide a proof-of-principle that local delivery of an immune factor, sFKN is effective in restoring ribbon synapses and hearing loss after NICS in a macrophage-dependent manner and highlights the potential of sFKN as an immunotherapy for cochlear synaptopathy due to noise.

Background Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems. We have developed an animal model of this human condition in the Mongolian Gerbil that uses surgically created SSCD to induce the condition. A feature that is unique in this model is that spontaneous resurfacing of the dehiscence occurs via osteoneogenesis without a subsequent intervention. In this study, we completed our assessment of this model to include reversible asymmetrical vestibular impairments that interfere with balance. Methods Adult Mongolian gerbils ( N = 6) were trained to complete a balance beam task. They were also trained to perform a Rotarod task. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Balance beam testing recommenced at postoperative day 6 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results Behavioral comparison of preoperative and postoperative performance show a significant decrease in Rotarod performance, increased rates of falling, and an increase in time to cross the balance beam. Impairments were the most significant at postoperative day 7 with a return toward preoperative performance by postoperative day 14. This behavioral impairment was correlated with residual impairments to auditory thresholds and vestibular myogenic amplitudes at postoperative day 14. Conclusion These results confirm that aberrant asymmetric vestibular output in our model of SSCD results in reversible balance impairments. The level of these behavioral impairments is directly correlated with severity of the vestibular dysfunction as we have previously reported for peripheral ear physiology and cognition.