ABR/DPOAE publications

Background The purpose of this study was to evaluate if kilohertz frequency alternating current (KHFAC) stimulation of peripheral nerve could serve as a treatment for lumbar radiculopathy. Prior work shows that KHFAC stimulation can treat sciatica resulting from chronic sciatic nerve constriction. Here, we evaluate if KHFAC stimulation is also beneficial in a more physiologic model of low back pain which mimics nucleus pulposus (NP) impingement of a lumbar dorsal root ganglion (DRG). Methods To mimic a lumbar radiculopathy, autologous tail NP was harvested and placed upon the right L5 nerve root and DRG. During the same surgery, a cuff electrode was implanted around the sciatic nerve with wires routed to a headcap for delivery of KHFAC stimulation. Male Lewis rats (3 mo., n = 18) were separated into 3 groups: NP injury + KHFAC stimulation ( n = 7), NP injury + sham cuff ( n = 6), and sham injury + sham cuff ( n = 5). Prior to surgery and for 2 weeks following surgery, animal tactile sensitivity, gait, and static weight bearing were evaluated. Results KHFAC stimulation of the sciatic nerve decreased behavioral evidence of pain and disability. Without KHFAC stimulation, injured animals had heightened tactile sensitivity compared to baseline ( p < 0.05), with tactile allodynia reversed during KHFAC stimulation ( p < 0.01). Midfoot flexion during locomotion was decreased after injury but improved with KHFAC stimulation ( p < 0.05). Animals also placed more weight on their injured limb when KHFAC stimulation was applied ( p < 0.05). Electrophysiology measurements at end point showed decreased, but not blocked, compound nerve action potentials with KHFAC stimulation ( p < 0.05). Conclusions KHFAC stimulation decreases hypersensitivity but does not cause additional gait compensations. This supports the idea that KHFAC stimulation applied to a peripheral nerve may be able to treat chronic pain resulting from sciatic nerve root inflammation.

Introduction Noise-induced calcium overload in sensory hair cells has been well documented as an early step in the pathogenesis of noise-induced hearing loss (NIHL). Alterations in cellular calcium homeostasis mediate a series of cellular events, including activation of calcium-dependent protein kinases and phosphatases. Using cell-membrane- and blood-brain-barrier-permeable calpain-1 (μ-calpain) and calpain-2 (m-calpain) inhibitor MDL-28170, we tested the involvement of calpains, a family of calcium-dependent cysteine proteases, and the potential of MDL-28170 in preventing NIHL. Methods CBA/J mice at the age of 12 weeks were exposed to broadband noise with a frequency spectrum from 2–20 kHz for 2 h at 101 dB sound pressure level to induce permanent hearing loss as measured by auditory brainstem response and distortion product otoacoustic emissions. Morphological damage was assessed by quantification of remaining sensory hair cells and inner hair cell synapses 2 weeks after the exposure. Results MDL-28170 treatment by intraperitoneal injection significantly attenuated noise-induced functional deficits and cochlear pathologies. MDL-28170 treatment also prevented noise-induced cleavage of alpha-fodrin, a substrate for calpain-1. Furthermore, MDL-28170 treatment prevented reduction of PI3K/Akt signaling after exposure to noise and upregulated p85α and p-Akt (S473) in outer hair cells. Discussion These results indicate that noise-induced calpain activation negatively regulates PI3K/Akt downstream signaling, and that prevention of NIHL by treatment with MDL-28170 is associated with upregulation of PI3K/Akt survival signaling pathways.

Background Otosclerosis is a common cause of adult-onset progressive hearing loss, affecting 0.3%–0.4% of the population. It results from dysregulation of bone homeostasis in the otic capsule, most commonly leading to fixation of the stapes bone, impairing sound conduction through the middle ear. Otosclerosis has a well-known genetic predisposition including familial cases with apparent autosomal dominant mode of inheritance. While linkage analysis and genome-wide association studies suggested an association with several genomic loci and with genes encoding structural proteins involved in bone formation or metabolism, the molecular genetic pathophysiology of human otosclerosis is yet mostly unknown. Methods Whole-exome sequencing, linkage analysis, generation of CRISPR mutant mice, hearing tests and micro-CT. Results Through genetic studies of kindred with seven individuals affected by apparent autosomal dominant otosclerosis, we identified a disease-causing variant in SMARCA4 , encoding a key component of the PBAF chromatin remodelling complex. We generated CRISPR-Cas9 transgenic mice carrying the human mutation in the mouse SMARCA4 orthologue. Mutant Smarca4 +/E1548K mice exhibited marked hearing impairment demonstrated through acoustic startle response and auditory brainstem response tests. Isolated ossicles of the auditory bullae of mutant mice exhibited a highly irregular structure of the incus bone, and their in situ micro-CT studies demonstrated the anomalous structure of the incus bone, causing disruption in the ossicular chain. Conclusion We demonstrate that otosclerosis can be caused by a variant in SMARCA4 , with a similar phenotype of hearing impairment and abnormal bone formation in the auditory bullae in transgenic mice carrying the human mutation in the mouse SMARCA4 orthologue.

TRPA1 channels are expressed in nociceptive neurons, where they detect noxious stimuli, and in the mammalian cochlea, where their function is unknown. Here we show that TRPA1 activation in the supporting non-sensory Hensen’s cells of the mouse cochlea causes prolonged Ca 2+ responses, which propagate across the organ of Corti and cause long-lasting contractions of pillar and Deiters’ cells. Caged Ca 2+ experiments demonstrated that, similar to Deiters’ cells, pillar cells also possess Ca 2+ -dependent contractile machinery. TRPA1 channels are activated by endogenous products of oxidative stress and extracellular ATP. Since both these stimuli are present in vivo after acoustic trauma, TRPA1 activation after noise may affect cochlear sensitivity through supporting cell contractions. Consistently, TRPA1 deficiency results in larger but less prolonged noise-induced temporary shift of hearing thresholds, accompanied by permanent changes of latency of the auditory brainstem responses. We conclude that TRPA1 contributes to the regulation of cochlear sensitivity after acoustic trauma.

Intrinsically generated neural activity propagates through the developing auditory system to promote maturation and refinement of sound processing circuits prior to hearing onset. This early patterned activity is induced by non-sensory supporting cells in the organ of Corti, which are highly interconnected through gap junctions containing connexin 26 ( Gjb2 ). Although loss of function mutations in Gjb2 impair cochlear development and are the most common cause of congenital deafness, it is not known if these variants disrupt spontaneous activity and the developmental trajectory of sound processing circuits in the brain. Here, we show in a new mouse model of Gjb2- mediated congenital deafness that cochlear supporting cells adjacent to inner hair cells (IHCs) unexpectedly retain intercellular coupling and the capacity to generate spontaneous activity, exhibiting only modest deficits prior to hearing onset. Supporting cells lacking Gjb2 elicited coordinated activation of IHCs, leading to coincident bursts of activity in central auditory neurons that will later process similar frequencies of sound. Despite alterations in the structure of the sensory epithelium, hair cells within the cochlea of Gjb2 -deficient mice were intact and central auditory neurons could be activated within appropriate tonotopic domains by loud sounds at hearing onset, indicating that early maturation and refinement of auditory circuits was preserved. Only after cessation of spontaneous activity following hearing onset did progressive hair cell degeneration and enhanced auditory neuron excitability manifest. This preservation of cochlear spontaneous neural activity in the absence of connexin 26 may increase the effectiveness of early therapeutic interventions to restore hearing.

Neurophysiological studies suggest that intrinsic brain oscillations influence sensory processing, especially of rhythmic stimuli like speech. Prior work suggests that brain rhythms may mediate perceptual grouping and selective attention to speech amidst competing sound, as well as more linguistic aspects of speech processing like predictive coding. However, we know of no prior studies that have directly tested, at the single-trial level, whether brain oscillations relate to speech-in-noise outcomes. Here, we combined electroencephalography while simultaneously measuring intelligibility of spoken sentences amidst two different interfering sounds: multi-talker babble or speech-shaped noise. We find that induced parieto-occipital alpha (7–15 Hz; thought to modulate attentional focus) and frontal beta (13–30 Hz; associated with maintenance of the current sensorimotor state and predictive coding) oscillations covary with trial-wise percent-correct scores; importantly, alpha and beta power provide significant independent contributions to predicting single-trial behavioral outcomes. These results can inform models of speech processing and guide noninvasive measures to index different neural processes that together support complex listening.

Relationships between novel phenotypic behaviors and specific genetic alterations are often discovered using target‐specific, directed mutagenesis or phenotypic selection following chemical mutagenesis. An alternative approach is to exploit deficiencies in DNA repair pathways that maintain genetic integrity in response to spontaneously induced damage. Mice deficient in the DNA glycosylase NEIL1 show elevated spontaneous mutations, which arise from translesion DNA synthesis past oxidatively induced base damage. Several litters of Neil1 knockout mice included animals that were distinguished by their backwards‐walking behavior in open‐field environments, while maintaining frantic forward movements in their home cage environment. Other phenotypic manifestations included swim test failures, head tilting and circling. Mapping of the mutation that conferred these behaviors showed the introduction of a stop codon at amino acid 4 of the Ush1g gene. Ush1g bw/bw null mice displayed auditory and vestibular defects that are commonly seen with mutations affecting inner‐ear hair‐cell function, including a complete lack of auditory brainstem responses and vestibular‐evoked potentials. As in other Usher syndrome type I mutant mouse lines, hair cell phenotypes included disorganized and split hair bundles, as well as altered distribution of proteins for stereocilia that localize to the tips of row 1 or row 2. Disruption to the bundle and kinocilium displacement suggested that USH1G is essential for forming the hair cell's kinocilial links. Consistent with other Usher type 1 models, Ush1g bw/bw mice had no substantial retinal degeneration compared with Ush1g bw /+ controls. In contrast to previously described Ush1g alleles, this new allele provides the first knockout model for this gene.

Prediction provides key advantages for survival, and cognitive studies have demonstrated that the brain computes multilevel predictions. Evidence for predictions remains elusive at the neuronal level because of the complexity of separating neural activity into predictions and stimulus responses. We overcome this challenge by recording from single neurons from cortical and subcortical auditory regions in anesthetized and awake preparations, during unexpected stimulus omissions interspersed in a regular sequence of tones. We find a subset of neurons that responds reliably to omitted tones. In awake animals, omission responses are similar to anesthetized animals, but larger and more frequent, indicating that the arousal and attentional state levels affect the degree to which predictions are neuronally represented. Omission-sensitive neurons also responded to frequency deviants, with their omission responses getting emphasized in the awake state. Because omission responses occur in the absence of sensory input, they provide solid and empirical evidence for the implementation of a predictive process.

Tightly regulated and robust mitochondrial activities are critical for normal hearing. Previously, we demonstrated that Fus1/Tusc2 KO mice with mitochondrial dysfunction exhibit premature hearing loss. Molecular analysis of the cochlea revealed hyperactivation of the mTOR pathway, oxidative stress, and altered mitochondrial morphology and quantity, suggesting compromised energy sensing and production. Here, we investigated whether the pharmacological modulation of metabolic pathways using rapamycin (RAPA) or 2-deoxy-D-glucose (2-DG) supplementation can protect against hearing loss in female Fus1 KO mice. Additionally, we aimed to identify mitochondria- and Fus1/Tusc2-dependent molecular pathways and processes critical for hearing. We found that inhibiting mTOR or activating alternative mitochondrial energetic pathways to glycolysis protected hearing in the mice. Comparative gene expression analysis revealed the dysregulation of critical biological processes in the KO cochlea, including mitochondrial metabolism, neural and immune responses, and the cochlear hypothalamic–pituitary–adrenal axis signaling system. RAPA and 2-DG mostly normalized these processes, although some genes showed a drug-specific response or no response at all. Interestingly, both drugs resulted in a pronounced upregulation of critical hearing-related genes not altered in the non-treated KO cochlea, including cytoskeletal and motor proteins and calcium-linked transporters and voltage-gated channels. These findings suggest that the pharmacological modulation of mitochondrial metabolism and bioenergetics may restore and activate processes critical for hearing, thereby protecting against hearing loss.

Objective: Distortion-product otoacoustic emission (DPOAE) levels are repeatable over time in normal-hearing individuals making DPOAE levels an ideal measurement for monitoring cochlear status in clinic and research applications. However, if DPOAE signal-to-noise ratio (SNR) values instead of levels are used for monitoring, the repeatability of this value needs to be established. This retrospective, cross-sectional study sought to determine DPOAE SNR repeatability in younger children, older children, young adults and a patient population with normal hearing. Design: Each participant attended four sessions where DPOAE discrete frequency sweeps were collected at conventional (≤ 8 kHz) and/or extended-high frequencies (> 8 kHz). To examine the extent of variability to be expected for DPOAE SNR, average absolute SNR differences-between-trials were determined and compared to average absolute DPOAE level differences-between-trials. Study samples: One hundred forty-five participants, incorporating four different groups from three different studies. Ages ranged from 3 to 55 years. Results: Average SNR differences-between-trials across all frequencies are greater than differences for average DPOAE levels. Improved calibration methods result in SNR differences-between-trials that are similar across all frequencies. Conclusions: When monitoring cochlear health over an extended bandwidth, DPOAE levels are less variable across trials than SNR values, thus allowing earlier indicators of cochlear damage.

Efferent brain-stem neurons release acetylcholine to desensitize cochlear hair cells and can protect the inner ear from acoustic trauma. That protection is absent from knockout mice lacking efferent inhibition and is stronger in mice with a gain-of-function point mutation of the hair cell-specific nicotinic acetylcholine receptor. The present work uses viral transduction of gain-of-function receptors to restore acoustic prophylaxis to the knockout mice. Widespread postsynaptic expression of the transgene was visualized in excised tissue with a fluorophore-conjugated peptide toxin that binds selectively to hair cell acetylcholine receptors. Viral transduction into efferent knockout mice reduced the temporary hearing loss measured 1 day post acoustic trauma. The acoustic evoked-response waveform (auditory brain-stem response) recovered more rapidly in treated mice than in control mice. Thus, both cochlear amplification by outer hair cells (threshold shift) and afferent signaling (evoked-response amplitude) in knockout mice were protected by viral transduction of hair cell acetylcholine receptors. Gene therapy to strengthen efferent cochlear feedback could be complementary to existing and future therapies to prevent hearing loss, including ear coverings, hearing aids, single-gene repair, or small-molecule therapies.

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5 (PRMT5) in cisplatin-induced hearing loss. The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry, apoptosis assays, and auditory brainstem response. The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction (CUT&Tag-qPCR) analyses in the HEI-OC1 cell line. Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species. CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene, thus activating the expression of Pik3ca. These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Hearing impairment without threshold elevations can occur when there is damage to high‐threshold auditory nerve fibre synapses with cochlear inner hair cells. Instead, cochlear synaptopathy produces suprathreshold deficits, especially in older patients, which affect conversational speech. Given that listening in noise at suprathreshold levels presents significant challenges to the ageing population, we examined the effects of synaptopathy on tone‐in‐noise coding on the central recipients of auditory nerve fibres, i.e. the cochlear nucleus neurons. To induce synaptopathy, guinea pigs received a unilateral sound overexposure to the left ears. A separate group received sham exposures. At 4 weeks post‐exposure, thresholds had recovered but reduced auditory brainstem response wave 1 amplitudes and auditory nerve synapse loss remained on the left side. Single‐unit responses were recorded from several cell types in the ventral cochlear nucleus to pure‐tone and noise stimuli. Receptive fields and rate–level functions in the presence of continuous broadband noise were examined. The synaptopathy‐inducing noise exposure did not affect mean unit tone‐in‐noise thresholds, nor the tone‐in‐noise thresholds in each animal, demonstrating equivalent tone‐in‐noise detection thresholds to sham animals. However, synaptopathy reduced single‐unit responses to suprathreshold tones in the presence of background noise, particularly in the cochlear nucleus small cells. These data demonstrate that suprathreshold tone‐in‐noise deficits following cochlear synaptopathy are evident in the first neural station of the auditory brain, the cochlear nucleus neurons, and provide a potential target for assessment and treatment of listening‐in‐noise deficits in humans. image Key points Recording from multiple central auditory neurons can determine tone‐in‐noise deficits in animals with quantified cochlear synapse damage. Using this technique, we found that tone‐in‐noise thresholds are not altered by cochlear synaptopathy, whereas coding of suprathreshold tones‐in‐noise is disrupted. Suprathreshold deficits occur in small cells and primary‐like neurons of the cochlear nucleus. These data provide important insights into the mechanisms underlying difficulties associated with hearing in noisy environments.

Isoforms of a gene may contribute to diverse biological functions. In the cochlea, the repertoire of alternative isoforms remains unexplored. We integrated single-cell short-read and long-read RNA sequencing techniques and identified 236,012 transcripts, 126,612 of which were unannotated in the GENCODE database. Then we analyzed and verified the unannotated transcripts using RNA-seq, RT-PCR, Sanger sequencing, and MS-based proteomics approaches. To illustrate the importance of identifying spliced isoforms, we investigated otoferlin, a key protein involved in synaptic transmission in inner hair cells (IHCs). Upon deletion of the canonical otoferlin isoform, the identified short isoform is able to support normal hearing thresholds but with reduced sustained exocytosis of IHCs, and further revealed otoferlin functions in endocytic membrane retrieval that was not well-addressed previously. Furthermore, we found that otoferlin isoforms are associated with IHC functions and auditory phenotypes. This work expands our mechanistic understanding of auditory functions at the level of isoform resolution.

Alzheimer’s Disease (AD) is a neurodegenerative illness without a cure. All current therapies require an accurate diagnosis and staging of AD to ensure appropriate care. Central auditory processing disorders (CAPDs) and hearing loss have been associated with AD, and may precede the onset of Alzheimer’s dementia. Therefore, CAPD is a possible biomarker candidate for AD diagnosis. However, little is known about how CAPD and AD pathological changes are correlated. In the present study, we investigated auditory changes in AD using transgenic amyloidosis mouse models. AD mouse models were bred to a mouse strain commonly used for auditory experiments, to compensate for the recessive accelerated hearing loss on the parent background. Auditory brainstem response (ABR) recordings revealed significant hearing loss, a reduced ABR wave I amplitude, and increased central gain in 5xFAD mice. In comparison, these effects were milder or reversed in APP/PS1 mice. Longitudinal analyses revealed that in 5xFAD mice, central gain increase preceded ABR wave I amplitude reduction and hearing loss, suggesting that it may originate from lesions in the central nervous system rather than the peripheral loss. Pharmacologically facilitating cholinergic signaling with donepezil reversed the central gain in 5xFAD mice. After the central gain increased, aging 5xFAD mice developed deficits for hearing sound pips in the presence of noise, consistent with CAPD-like symptoms of AD patients. Histological analysis revealed that amyloid plaques were deposited in the auditory cortex of both mouse strains. However, in 5xFAD but not APP/PS1 mice, plaque was observed in the upper auditory brainstem, specifically the inferior colliculus (IC) and the medial geniculate body (MGB). This plaque distribution parallels histological findings from human subjects with AD and correlates in age with central gain increase. Overall, we conclude that auditory alterations in amyloidosis mouse models correlate with amyloid deposits in the auditory brainstem and may be reversed initially through enhanced cholinergic signaling. The alteration of ABR recording related to the increase in central gain prior to AD-related hearing disorders suggests that it could potentially be used as an early biomarker of AD diagnosis.

Alterations in neuronal plasticity and critical periods are common across neurodevelopmental diseases, including Fragile X syndrome (FXS), the leading single-gene cause of autism. Characterized with sensory dysfunction, FXS is the result of gene silencing of Fragile X messenger ribonucleoprotein 1 (FMR1) and loss of its product, Fragile X messenger ribonucleoprotein (FMRP). The mechanisms underlying altered critical period and sensory dysfunction in FXS are obscure. Here, we performed genetic and surgical deprivation of peripheral auditory inputs in wildtype and Fmr1 knockout (KO) mice across ages and investigated the effects of global FMRP loss on deafferentation-induced neuronal changes in the ventral cochlear nucleus (VCN) and auditory brainstem responses. The degree of neuronal cell loss during the critical period was unchanged in Fmr1 KO mice. However, the closure of the critical period was delayed. Importantly, this delay was temporally coincidental with reduced hearing sensitivity, implying an association with sensory inputs. Functional analyses further identified early-onset and long-lasting alterations in signal transmission from the spiral ganglion to the VCN, suggesting a peripheral site of FMRP action. Finally, we generated conditional Fmr1 KO (cKO) mice with selective deletion of FMRP in spiral ganglion but not VCN neurons. cKO mice recapitulated the delay in the VCN critical period closure in Fmr1 KO mice, confirming an involvement of cochlear FMRP in shaping the temporal features of neuronal critical periods in the brain. Together, these results identify a novel peripheral mechanism of neurodevelopmental pathogenesis.

The cochlea hair cells transform mechanic sounds to neural signals with a remarkable sensitivity and resolution. This is achieved via the precisely sculpted mechanotransduction apparatus of the hair cells and the supporting structure of the cochlea. The shaping of the mechanotransduction apparatus, the staircased stereocilia bundles on the apical surface of the hair cells, requires an intricate regulatory network including planar cell polarity (PCP) and primary cilia genes in orienting stereocilia bundles and building molecular machinery of the apical protrusions. The mechanism linking these regulatory components is unknown. Here, we show that a small GTPase known for its role in protein trafficking, Rab11a, is required for ciliogenesis in hair cells during development in mice. In addition, in the absence of Rab11a, stereocilia bundles lost their cohesion and integrity, and mice are deaf. These data indicate an essential role of protein trafficking in the formation of hair cell mechanotransduction apparatus, implicating a role of Rab11a or protein trafficking in linking the cilia and polarity regulatory components with the molecular machinery in building the cohesive and precisely shaped stereocilia bundles.

Mutations in GJB2 (Gap junction protein beta 2) are the most common genetic cause of non-syndromic hereditary deafness in humans, especially the 35delG and 235delC mutations. Owing to the homozygous lethality of Gjb2 mutations in mice, there are currently no perfect mouse models carrying Gjb2 mutations derived from patients for mimicking human hereditary deafness and for unveiling the pathogenesis of the disease. Here, we successfully constructed heterozygous Gjb2 + /35delG and Gjb2 + /235delC mutant mice through advanced androgenic haploid embryonic stem cell (AG-haESC)-mediated semi-cloning technology, and these mice showed normal hearing at postnatal day (P) 28. A homozygous mutant mouse model, Gjb2 35delG/35delG , was then generated using enhanced tetraploid embryo complementation, demonstrating that GJB2 plays an indispensable role in mouse placenta development. These mice exhibited profound hearing loss similar to human patients at P14, i.e., soon after the onset of hearing. Mechanistic analyses showed that Gjb2 35delG disrupts the function and formation of intercellular gap junction channels of the cochlea rather than affecting the survival and function of hair cells. Collectively, our study provides ideal mouse models for understanding the pathogenic mechanism of DFNB1A-related hereditary deafness and opens up a new avenue for investigating the treatment of this disease.

The peroxisome is a ubiquitous organelle in rodent cells and plays important roles in a variety of cell types and tissues. It is previously indicated that peroxisomes are associated with auditory function, and patients with peroxisome biogenesis disorders (PBDs) are found to have hearing dysfunction, but the specific role of peroxisomes in hearing remains unclear. In this study, two peroxisome‐deficient mouse models ( Atoh1‐Pex5 −/− and Pax2‐Pex5 −/− ) are established and it is found that peroxisomes mainly function in the hair cells of cochleae. Furthermore, peroxisome deficiency‐mediated negative effects on hearing do not involve mitochondrial dysfunction and oxidative damage. Although the mammalian target of rapamycin complex 1 (mTORC1) signaling is shown to function through peroxisomes, no changes are observed in the mTORC1 signaling in Atoh1‐Pex5 −/‐ mice when compared to wild‐type (WT) mice. However, the expression of large‐conductance, voltage‐, and Ca2 + ‐activated K + (BK) channels is less in Atoh1‐Pex5 −/− mice as compared to the WT mice, and the administration of activators of BK channels (NS‐1619 and NS‐11021) restores the auditory function in knockout mice. These results suggest that peroxisomes play an essential role in cochlear hair cells by regulating BK channels. Hence, BK channels appear as the probable target for treating peroxisome‐related hearing diseases such as PBDs.

Synopsis According to the World Health Organization, ∼15 million children are born prematurely each year. Many of these infants end up spending days to weeks in a neonatal intensive care unit (NICU). Infants who are born prematurely are often exposed to noise and light levels that affect their auditory and visual development. Children often have long-term impairments in cognition, visuospatial processing, hearing, and language. We have developed a rodent model of NICU exposure to light and sound using the Mongolian gerbil (Meriones unguiculatus), which has a low-frequency human-like audiogram and is altricial. To simulate preterm infancy, the eyes and ears were opened prematurely, and animals were exposed to the NICU-like sensory environment throughout the gerbil’s cortical critical period of auditory development. After the animals matured into adults, auditory perceptual testing was carried out followed by auditory brainstem response recordings and then histology to assess the white matter morphology of various brain regions. Compared to normal hearing control animals, NICU sensory-exposed animals had significant impairments in learning at later stages of training, increased auditory thresholds reflecting hearing loss, and smaller cerebellar white matter volumes. These have all been reported in longitudinal studies of preterm infants. These preliminary results suggest that this animal model could provide researchers with an ethical way to explore the effects of the sensory environment in the NICU on the preterm infant’s brain development.