ABR/DPOAE publications

The neurochemical serotonin (5-hydroxytryptamine, 5-HT) is involved in a variety of behavioral functions including arousal, reward, and attention, and has a role in several complex disorders of the brain. In the auditory system, 5-HT fibers innervate a number of subcortical nuclei, yet the modulatory role of 5-HT in nearly all of these areas remains poorly understood. In this study, we examined spiking activity of neurons in the dorsal cochlear nucleus (DCN) following iontophoretic application of 5-HT. The DCN is an early site in the auditory pathway that receives dense 5-HT fiber input from the raphe nuclei and has been implicated in the generation of auditory disorders marked by neuronal hyperexcitability. Recordings from the DCN in awake mice demonstrated that iontophoretic application of 5-HT had heterogeneous effects on spiking rate, spike timing, and evoked spiking threshold. We found that 56% of neurons exhibited increases in spiking rate during 5-HT delivery, while 22% had decreases in rate and the remaining neurons had no change. These changes were similar for spontaneous and evoked spiking and were typically accompanied by changes in spike timing. Spiking increases were associated with lower first spike latencies and jitter, while decreases in spiking generally had opposing effects on spike timing. Cases in which 5-HT application resulted in increased spiking also exhibited lower thresholds compared to the control condition, while cases of decreased spiking had no threshold change. We also found that the 5-HT2 receptor subtype likely has a role in mediating increased excitability. Our results demonstrate that 5-HT can modulate activity in the DCN of awake animals and that it primarily acts to increase neuronal excitability, in contrast to other auditory regions where it largely has a suppressive role. Modulation of DCN function by 5-HT has implications for auditory processing in both normal hearing and disordered states.

In auditory pathways, the precision of action potential (AP) propagation depends on axon myelination and high densities of voltage-gated Na (Na v ) channels clustered at nodes of Ranvier. Changes in Na v channel expression at the heminode, the final node before the nerve terminal, can alter AP invasion into the presynaptic terminal. We studied the activity-dependent formation of Na v channel clusters before and after hearing onset at postnatal day 12 in the rat and mouse auditory brain stem. In rats, the Na v channel cluster at the heminode formed progressively during the second postnatal week, around hearing onset, whereas the Na v channel cluster at the nodes was present before hearing onset. Initiation of heminodal Na v channel clustering was correlated with the expression of scaffolding protein ankyrinG and paranodal protein Caspr. However, in whirler mice with congenital deafness, heminodal Na v channels did not form clusters and maintained broad expression, but Na v channel clustering was normal at the nodes. In addition, a clear difference in the distance from the heminodal Na v channel to the calyx across the mediolateral axis of the medial nucleus of the trapezoid body (MNTB) developed after hearing onset. In the medial MNTB, where neurons respond best to high-frequency sounds, the heminodal Na v channel cluster was located closer to the terminal than in the lateral MNTB, where neurons respond best to low-frequency sounds. Thus sound-mediated neuronal activities are potentially associated with the refinement of the heminode adjacent to the presynaptic terminal in the auditory brain stem. NEW & NOTEWORTHY Clustering of voltage-gated sodium (Na v ) channels and their distribution along the axon, specifically at the unmyelinated axon segment next to the nerve terminal, are essential for tuning propagated action potentials. Na v channel clusters near the nerve terminal and their location as a function of neuronal position along the mediolateral axis are controlled by auditory inputs after hearing onset. Thus sound-mediated neuronal activity influences the tonotopic organization of Na v channels at the nerve terminal in the auditory brain stem.

The cochlear blood-labyrinth barrier (BLB), located in the stria vascularis, is critical for the homeostasis of cochlear solutes and ion transport. Significant disruption to the BLB occurs early during noise‑induced hearing loss. Matrix metalloproteinase (MMP)‑2 and ‑9 are important molecules known to be capable of degrading tight junction (TJ) proteins. The TJ proteins are important components of the extracellular matrix (ECM), required to maintain BLB integrity and permeability. Previous studies have demonstrated that MMP‑2 and ‑9, rich in healthy cochlea, serve an essential role in regulating the cochlear response to acoustic trauma. The present study investigated the localization and function of MMP‑2 and ‑9 in the BLB by determining their associated gene expression and activity under normal conditions and after noise exposure. Analysis of gene expression by RNA‑sequencing (RNA‑seq) revealed expression of 15 MMP‑associated genes, including genes for MMP‑2 and ‑9, in healthy stria vascularis. Expression of these MMP genes was dynamically regulated by noise trauma to the cochlea, and accompanied by alterations in tissue inhibitors of metalloproteinases (TIMPs) and the TJ protein zona‑occludens 1 (ZO‑1). These alterations suggested that MMP‑2 and ‑9 serve an important role in maintaining the integrity of BLB and in response to acoustic trauma. MMP‑2, MMP‑9 and ZO‑1 protein expression levels in the stria vascularis by immunofluorescence, and observed that the stable expression of MMP-2 and ‑9 in healthy stria was markedly increased following noise exposure, consistent with the RNA‑seq results. The compact structure of ZO‑1 in the BLB loosened, and strial capillaries exhibited markedly increased leakage of Evans blue dye following acoustic trauma. These data indicated that mediation of MMP‑2 and ‑9 in structural damage to TJ proteins, including ZO‑1, may be an important mechanism in the breakdown of the BLB following acoustic trauma. Additionally, these results indicated that MMPs are involved in regulating the integrity and permeability of the BLB, which may provide a theoretical basis for the prevention of noise‑induced hearing loss.

Aminoglycoside antibiotics including gentamicin (GM) induce delayed ototoxic effects such as hearing loss after long-term use, unlike the early-onset ototoxicity caused by cisplatin. The purpose of the study was to identify the mechanism of the delayed GM-induced ototoxicity by exploring the role of autophagy in vitro and in vivo . Treating HEI-OC1 auditory cells with GM led to a time-dependent increase of the autophagosome marker LC3-II, which was accompanied by cell death. In contrast, cisplatin and penicillin caused a rapid increase and had no effect on LC3-II levels, respectively. LC3-II-expressing autophagosomes co-localized with the labeled GM. GM-treated autophagosomes expressed reduced levels of Rab7, which is necessary for the fusion of autophagosomes with lysosomes. When the autophagic flux enhancer rapamycin was applied to GM-treated cells, Rab7 and the lysosomal enzyme cathepsin D were upregulated, and increased cell survival was observed. In animal studies, the intraperitoneal injection of GM worsened hearing thresholds and induced the accumulation of LC3 in the organ of Corti. This hearing impairment was attenuated by rapamycin. These findings suggest that the delayed onset-ototoxicity of GM may be closely related to the accumulation of autophagosomes via impaired autophagy. This GM-induced auditory cell death could be inhibited by enhancing autophagic flux.

Cellular asymmetries play crucial roles in development and organ function. The planar cell polarity (PCP) signaling pathway is involved in the establishment of cellular asymmetry within the plane of a cell sheet. Inner ear sensory hair cells (HCs), which have several rows of staircase-like stereocilia and one kinocilium located at the vertex of the stereocilia protruding from the apical surface of each HC, exhibit a typical form of PCP. Although connections between cilia and PCP signaling in vertebrate development have been reported, their precise nature is not well understood. During inner ear development, several ciliary proteins are known to play a role in PCP formation. In the current study, we investigated a functional role for intestinal cell kinase (Ick), which regulates intraflagellar transport (IFT) at the tip of cilia, in the mouse inner ear. A lack of Ick in the developing inner ear resulted in PCP defects in the cochlea, including misorientation or misshaping of stereocilia and aberrant localization of the kinocilium and basal body in the apical and middle turns, leading to auditory dysfunction. We also observed abnormal ciliary localization of Ift88 in both HCs and supporting cells. Together, our results show that Ick ciliary kinase is essential for PCP formation in inner ear HCs, suggesting that ciliary transport regulation is important for PCP signaling. SIGNIFICANCE STATEMENT The cochlea in the inner ear is the hearing organ. Planar cell polarity (PCP) in hair cells (HCs) in the cochlea is essential for mechanotransduction and refers to the asymmetric structure consisting of stereociliary bundles and the kinocilium on the apical surface of the cell body. We reported previously that a ciliary kinase, Ick, regulates intraflagellar transport (IFT). Here, we found that loss of Ick leads to abnormal localization of the IFT component in kinocilia, PCP defects in HCs, and hearing dysfunction. Our study defines the association of ciliary transport regulation with PCP formation in HCs and hearing function.

Auditory nerve fibers (ANFs) transmit acoustic information from the sensory hair cells to the cochlear nuclei. In experimental and clinical audiology, probing the whole ANF population remains a difficult task, as the ANFs differ greatly in their threshold and onset response to sound. Thus, low spontaneous rate (SR) fibers, which have rather higher thresholds, delay and larger jitter in their first spike latency are not detectable in the far-field compound action potential of the auditory nerve. Here, we developed a new protocol of acoustic stimulation together with electrophysiological signal processing to track the steady state activity of ANFs. Mass potentials at the round window were recorded in response to repetitive 300-ms bursts of 1/3 octave band noise centered on a frequency probe. Analysis was assessed during the last 200-ms of the response to capture the steady-state response of ANFs. To eliminate the microphonic component reflecting the sensory cells activity, repetitive pairs of sounds of opposite polarities were used. The spectral analysis was calculated on the average of two consecutive responses, and the neural gain was calculated by dividing point-by-point the spectrum to sound over unstimulated condition. In response to low-sound-level stimulation, neural gain predominated in the low-frequency cochlear regions, while a second component of responses centered on higher cochlear frequency regions appeared beyond 30 dB SPL. At 60 dB SPL, neural gain showed a bimodal shape, with a notch near 5.6 kHz. In addition to correlate with the functional mapping of ANFs along the tonotopic axis, the deletion of low-SR fibers leads to a reduction in the high-frequency response, where the low-SR fibers are preferentially located. Thus, mass potentials at the round window may provide a useful tool to probe the SR-based distribution of ANFs in humans and in other species in which direct single-unit recordings are difficult to achieve or not feasible.

Extensive research on humans has improved our understanding of how the brain integrates information from our different senses, and has begun to uncover the brain regions and large-scale neural activity that contributes to an observer's ability to perceive the relative timing of auditory and visual stimuli. In the present study, we developed the first behavioral tasks to assess the perception of audiovisual temporal synchrony in rats. Modeled after the parameters used in human studies, separate groups of rats were trained to perform: (1) a simultaneity judgment task in which they reported whether audiovisual stimuli at various stimulus onset asynchronies (SOAs) were presented simultaneously or not; and (2) a temporal order judgment task in which they reported whether they perceived the auditory or visual stimulus to have been presented first. Furthermore, using in vivo electrophysiological recordings in the lateral extrastriate visual (V2L) cortex of anesthetized rats, we performed the first investigation of how neurons in the rat multisensory cortex integrate audiovisual stimuli presented at different SOAs. As predicted, rats (n = 7) trained to perform the simultaneity judgment task could accurately (~80%) identify synchronous vs. asynchronous (200 ms SOA) trials. Moreover, the rats judged trials at 10 ms SOA to be synchronous, whereas the majority (~70%) of trials at 100 ms SOA were perceived to be asynchronous. During the temporal order judgment task, rats (n = 7) perceived the synchronous audiovisual stimuli to be "visual first" for ~52% of the trials, and calculation of the smallest timing interval between the auditory and visual stimuli that could be detected in each rat (i.e., the just noticeable difference (JND)) ranged from 77 ms to 122 ms. Neurons in the rat V2L cortex were sensitive to the timing of audiovisual stimuli, such that spiking activity was greatest during trials when the visual stimulus preceded the auditory by 20-40 ms. Ultimately, given that our behavioral and electrophysiological results were consistent with studies conducted on human participants and previous recordings made in multisensory brain regions of different species, we suggest that the rat represents an effective model for studying audiovisual temporal synchrony at both the neuronal and perceptual level.

Anesthesia is known to affect the auditory brainstem response (ABR) in mice, rats, birds and lizards. The present study investigated how the level of anesthesia affects ABR recordings in an amphibian species, Babina daunchina. To do this, we compared ABRs evoked by tone pip stimuli recorded from 35 frogs when Tricaine methane sulphonate (MS-222) anesthetic immersion times varied from 0, 5 and 10 minutes after anesthesia induction at sound frequencies between 0.5 and 6 kHz. ABR thresholds increased significantly with immersion time across the 0.5 kHz to 2.5 kHz frequency range, which is the most sensitive frequency range for hearing and the main frequency range of male calls. There were no significant differences for anesthetic levels across the 3 kHz to 6 kHz range. ABR latency was significantly longer in the 10 min group than in the 0 and 5 min groups at frequencies of 0.5, 1.0, 1.5, 2.5 kHz, while ABR latency did not differ across the 3 kHz to 4 kHz range and at 2.0 kHz. Taken together, these results show that the level of anesthesia affects the amplitude, threshold and latency of ABRs in frogs.

The purpose of this study was to test the hypothesis that listeners with frequent exposure to loud music exhibit deficits in suprathreshold auditory performance consistent with cochlear synaptopathy. Young adults with normal audiograms were recruited who either did ( n = 31) or did not ( n = 30) have a history of frequent attendance at loud music venues where the typical sound levels could be expected to result in temporary threshold shifts. A test battery was administered that comprised three sets of procedures: (a) electrophysiological tests including distortion product otoacoustic emissions, auditory brainstem responses, envelope following responses, and the acoustic change complex evoked by an interaural phase inversion; (b) psychoacoustic tests including temporal modulation detection, spectral modulation detection, and sensitivity to interaural phase; and (c) speech tests including filtered phoneme recognition and speech-in-noise recognition. The results demonstrated that a history of loud music exposure can lead to a profile of peripheral auditory function that is consistent with an interpretation of cochlear synaptopathy in humans, namely, modestly abnormal auditory brainstem response Wave I/Wave V ratios in the presence of normal distortion product otoacoustic emissions and normal audiometric thresholds. However, there were no other electrophysiological, psychophysical, or speech perception effects. The absence of any behavioral effects in suprathreshold sound processing indicated that, even if cochlear synaptopathy is a valid pathophysiological condition in humans, its perceptual sequelae are either too diffuse or too inconsequential to permit a simple differential diagnosis of hidden hearing loss.

Objectives . As a homing factor of stem cell, stromal derived factor-1 (SDF-1) is important for the regenerative research in ototoxicity. Mice models with aminoglycoside ototoxicity have been widely used to study the regeneration capacity of MSCs in repair of cochlear injury. We developed a mouse model with maximal increase in SDF-1 levels in the inner ear, according to the “one-shot” doses of kanamycin and furosemide. Methods . C57BL/6 mice had kanamycin (420, 550, and 600 mg/kg) dissolved in PBS, followed by an intraperitoneal injection of furosemide (130 mg/kg). The injuries of inner ear were measured with hearing thresholds, histology, and outer hair cell counts at 0, 3, 5, 7, 10, and 14 days before the sacrifice. The levels of SDF-1 in the inner ear were tested by real-time RT-PCR and immunohistochemistry. Results . There were a significant reduction in hearing thresholds and a maximal increase of SDF-1 levels in the furosemide 130 mg/kg + kanamycin 550 mg/kg group, but severe hearing deterioration over time was observed in the furosemide 130 mg/kg + kanamycin 600 mg/kg group and four mice were dead. SDF-1 was detected mostly in the stria vascularis and organ of Corti showing the highest increase in expression. Conclusion . We observed optimal induction of the stem cell homing factor in the newly generated aminoglycoside-induced ototoxicity mouse model using a “one-shot” protocol. This study regarding high SDF-1 levels in our mouse model of ototoxicity would play a major role in the development of therapeutic agents using MSC homing.

Noise‐induced hearing loss (NIHL) results from the damage of the delicate hair cells inside the ear after excessive stimulation of noise. Unlike certain lower animals such as amphibians, fishes, and birds, in humans, hair cells cannot be regenerated once they are killed or damaged; thus, there are no therapeutic options to cure NIHL. Therefore, it is more important to protect hair cells from the noise before the damage occurs. In this study, we report the protective effect of Yang Mi Ryung extract (YMRE) against NIHL; this novel therapeutic property of YMRE has not been reported previously. Our data demonstrates that the hearing ability damaged by noise is markedly restored in mice preadministrated with YMRE before noise exposure, to the level of normal control group. Our study also provides the molecular mechanism underlying the protective effect of YMRE against NIHL by showing that YMRE significantly blocks noise‐induced apoptotic cell death and reduces reactive oxygen species (ROS) production in cochleae. Moreover, quantitative polymerase chain reaction (qPCR) analysis demonstrates that YMRE has anti‐inflammatory properties, suppressing the mRNA levels of TNF α and IL‐1 β induced by noise exposure. In conclusion, YMRE could be a useful preventive intervention to prevent hearing impairment induced by the exposure to excessive noise.

MEIS1 is a developmental transcription factor linked to restless legs syndrome (RLS) in genome-wide association studies. RLS is a movement disorder leading to severe sleep reduction and with significant impact on the quality-of-life of patients. In genome-wide association studies, MEIS1 has consistently been the gene with the highest effect size and functional studies suggest a disease-relevant downregulation. Therefore, haploinsufficiency of Meis1 could be the most potential system for modeling RLS in animals. We used heterozygous Meis1 knock-out mice to study the effects of Meis1 haploinsufficiency on mouse behavioral and neurological phenotypes, and to relate the findings to human RLS. We exposed the Meis1-deficient mice to assays of motor, sensorimotor and cognitive ability and assessed the effect of a dopaminergic receptor 2/3 agonist commonly used in the treatment of RLS. The mutant mice showed a pattern of circadian hyperactivity, compatible with human RLS. Moreover, we discovered a replicable prepulse inhibition (PPI) deficit in the Meis1-deficient animals. In addition, these mice were hyposensitive to the PPI-reducing effect of the dopaminergic receptor agonist, highlighting a role of Meis1 in the dopaminergic system. Other reported phenotypes include enhanced social recognition at an older age that was not related to alterations in adult olfactory bulb neurogenesis previously shown to be implicated in this behavior. In conclusion, the Meis1-deficient mice fulfill some of the hallmarks of an RLS animal model, and revealed the role of Meis1 in sensorimotor gating and in the dopaminergic systems modulating it.

Cochlear hair cells and the stria vascularis are critical for normal hearing. Hair cells transduce mechanical stimuli into electrical signals, whereas the stria is responsible for generating the endocochlear potential (EP), which is the driving force for hair cell mechanotransduction. We questioned whether hair cells and the stria interdepend for survival by using two mouse models. Atoh1 conditional knockout mice, which lose all hair cells within four weeks after birth, were used to determine whether the absence of hair cells would affect function and survival of stria. We showed that stria morphology and EP remained normal for long time despite a complete loss of all hair cells. We then used a mouse model that has an abnormal stria morphology and function due to mutation of the Mitf gene to determine whether hair cells are able to survive and transduce sound signals without a normal electrochemical environment in the endolymph. A strial defect, reflected by missing intermediate cells in the stria and by reduction of EP, led to systematic outer hair cell death from the base to the apex after postnatal day 18. However, an 18-mV EP was sufficient for outer hair cell survival. Surprisingly, inner hair cell survival was less vulnerable to reduction of the EP. Our studies show that normal function of the stria is essential for adult outer hair cell survival, while the survival and normal function of the stria vascularis do not depend on functional hair cells.

The matched filter hypothesis proposes that the tuning of auditory sensitivity and the spectral character of calls will match in order to maximize auditory processing efficiency during courtship. In this study, we analyzed the acoustic structure of male calls and both male and female hearing sensitivities in the little torrent frog ( Amolops torrentis ), an anuran species who transmits acoustic signals across streams. The results were in striking contradiction to the matched filter hypothesis. Auditory brainstem response results showed that the best hearing range was 1.6–2 kHz consistent with the best sensitive frequency of most terrestrial lentic taxa, yet completely mismatched with the dominant frequency of conspecific calls (4.3 kHz). Moreover, phonotaxis tests show that females strongly prefer high‐frequency (4.3 kHz) over low‐frequency calls (1.6 kHz) regardless of ambient noise levels, although peripheral auditory sensitivity is highest in the 1.6–2 kHz range. These results are consistent with the idea that A. torrentis evolved from nonstreamside species and that high‐frequency calls evolved under the pressure of stream noise. Our results also suggest that female preferences based on central auditory system characteristics may evolve independently of peripheral auditory system sensitivity in order to maximize communication effectiveness in noisy environments.

Ca2+ signaling has been implicated in the initial pathophysiologic mechanisms underlying the cochlea's response to acoustic overstimulation. Intracellular Ca2+ signaling (ICS) waves, which occur in glia and retinal cells in response to injury to activate cell regulatory pathways, have been proposed as an early event in cochlear injury. Disruption of ICS activity is thought to underlie Connexin 26-associated hearing loss, the most common genetic form of deafness, and downstream sequelae of ICS wave activity, such as MAP kinase pathway activation, have been implicated in noise-induced hearing loss. However, ICS waves have only been observed in neonatal cochlear cultures and are thought to be quiescent after the onset of hearing. In this study, we employ an acute explant model of an adult, hearing cochlea that retains many in vivo physiologic features to investigate Ca2+ changes in response to sound. We find that both slow monotonic changes in intracellular Ca2+ concentration as well as discrete ICS waves occur with acoustic overstimulation. The ICS waves share many intrinsic features with their better-described neonatal counterparts, including ATP and gap-junction dependence, and propagation velocity and distance. This identification of ICS wave activity in the adult, hearing cochlea thus confirms and characterizes an important early detection mechanism for cochlear trauma and provides a target for interventions for noise-induced and Connexin 26-associated hearing loss.

Cisplatin-induced ototoxicity remains a primary dose-limiting adverse effect of this highly effective anticancer drug. The clinical utility of cisplatin could be enhanced if the signaling pathways that regulate the toxic side-effects are delineated. In previous studies, we reported cisplatin-induced nitration of cochlear proteins and provided the first evidence for nitration and downregulation of cochlear LIM domain only 4 (LMO4) in cisplatin ototoxicity. Here, we extend these findings to define the critical role of nitrative stress in cisplatin-induced downregulation of LMO4 and its consequent ototoxic effects in UBOC1 cell cultures derived from sensory epithelial cells of the inner ear and in CBA/J mice. Cisplatin treatment increased the levels of nitrotyrosine and active caspase 3 in UBOC1 cells, which was detected by immunocytochemical and flow cytometry analysis, respectively. The cisplatin-induced nitrative stress and apoptosis were attenuated by co-treatment with SRI110, a peroxynitrite decomposition catalyst (PNDC), which also attenuated the cisplatin-induced downregulation of LMO4 in a dose-dependent manner. Furthermore, transient overexpression of LMO4 in UBOC1 cells prevented cisplatin-induced cytotoxicity while repression of LMO4 exacerbated cisplatin-induced cell death, indicating a direct link between LMO4 protein levels and cisplatin ototoxicity. Finally, auditory brainstem responses (ABR) recorded from CBA/J mice indicated that co-treatment with SRI110 mitigated cisplatin-induced hearing loss. Together, these results suggest that cisplatin-induced nitrative stress leads to a decrease in the levels of LMO4, downregulation of LMO4 is a critical determinant in cisplatin-induced ototoxicity, and targeting peroxynitrite could be a promising strategy for mitigating cisplatin-induced hearing loss.

Age-related hearing loss (ARHL) is largely attributed to structural changes and functional declines in the peripheral auditory system, which include synaptopathy at the inner hair cell/spiral ganglion cell (SGC) connection and the loss of SGCs. However, functional changes at the central terminals of SGCs, namely the auditory nerve synapses in the cochlear nucleus, are not yet fully understood during ARHL. With the use of young (1–3 mo) and old (25–30 mo) CBA/CaJ mice, this study evaluated the intrinsic properties of the bushy neurons postsynaptic to the endbulb of Held synapses, and the firing properties of these neurons to direct current injections as well as to synaptic inputs from the auditory nerve. Results showed that bushy neurons in old mice are more excitable and are able to fire spikes at similar rate and timing to direct current injections as those in young mice. In response to synaptic inputs, however, bushy neurons from old mice fired spikes with significantly decreased rate and reduced temporal precision to stimulus trains at 100 and 400 Hz, with the drop in firing probability more profound at 400 Hz. It suggests that transmission of auditory information at the endbulb is declined in both rate and timing during aging, which signifies the loss of sensory inputs to the central auditory system under ARHL. The study proposes that, in addition to damages at the peripheral terminals of SGCs as well as the loss of SGCs, functional decline at the central terminals of surviving SGCs is also an essential component of ARHL.

Sound energy propagates in the cochlea through a forward-traveling or slow wave supported by the cochlear partition and fluid inertia. Additionally, cochlear models support traveling wave propagation in the reverse direction as the expected mechanism for conveying otoacoustic emissions out of the cochlea. Recently, however, this hypothesis has been questioned, casting doubt on the process by which otoacoustic emissions travel back out through the cochlea. The proposed alternative reverse travel path for emissions is directly through the fluids of the cochlea as a compression pressure in the form of a fast wave. In the present study, a custom-made micro-pressure sensor was used in vivo in the gerbil cochlea to map two-tone-evoked pressure responses at distinct longitudinal and vertical locations in both the scala tympani and scala vestibuli. Analyses of the magnitude and phase of intracochlear pressure responses at the primary tone and distortion product frequencies were used to distinguish between fast and slow waves in both the forward- and reverse-propagation directions. Results demonstrated that distortion products may travel in both forward and reverse directions post-generation and the existence of both traveling and compression waves. The forward-traveling component appeared to duplicate the process of any external tone, tuned to the local characteristic-frequency place, as it increased compressively and nonlinearly with primary-tone levels. A compression wave was evidenced at frequencies above the cutoff of the recording site. In the opposite direction, a reverse-traveling wave played the major role in driving the stapes reversely and contributed to the distortion product otoacoustic emission. The compression wave may also play a role in reverse propagation when distortion products are generated at a region close to the stapes.

Tinnitus chronically affects between 10–15% of the population but, despite its prevalence, the underlying mechanisms are still not properly understood. One experimental model involves administration of high doses of sodium salicylate, as this is known to reliably induce tinnitus in both humans and animals. Guinea pigs were implanted with chronic electrocorticography ( EC oG) electrode arrays, with silver‐ball electrodes placed on the dura over left and right auditory cortex. Two more electrodes were positioned over the cerebellum to monitor auditory brainstem responses ( ABR s). We recorded resting‐state and auditory evoked neural activity from awake animals before and 2 h following salicylate administration (350 mg/kg; i.p.). Large increases in click‐evoked responses (> 100%) were evident across the whole auditory cortex, despite significant reductions in wave I ABR amplitudes (in response to 20 kHz tones), which are indicative of auditory nerve activity. In the same animals, significant decreases in 6–10 Hz spontaneous oscillations (alpha waves) were evident over dorsocaudal auditory cortex. We were also able to demonstrate for the first time that cortical evoked potentials can be inhibited by a preceding gap in background noise [gap‐induced pre‐pulse inhibition ( PPI )], in a similar fashion to the gap‐induced inhibition of the acoustic startle reflex that is used as a behavioural test for tinnitus. Furthermore, 2 h following salicylate administration, we observed significant deficits in PPI of cortical responses that were closely aligned with significant deficits in behavioural responses to the same stimuli. Together, these data are suggestive of neural correlates of tinnitus and oversensitivity to sound (hyperacusis).