Erratum to "Noise-induced changes of neuronal spontaneous activity in mice inferior colliculus brain slices"

The inferior colliculus (IC) in vivo is reportedly subject to a noise-induced decrease of GABA-related inhibitory synaptic transmission accompanied by an amplitude increase of auditory evoked responses, a widening of tuning curves and a higher neuronal discharge rate at suprathreshold levels. However, other in vivo experiments which demonstrated constant neuronal auditory thresholds or unchanged spontaneous activity in the IC after noise exposure did not confirm those findings. Perhaps this can be the result of complex noise-induced interactions between different central auditory structures. It was, therefore, the aim of the present study to investigate the effects of noise exposure on the spontaneous electrical activity of single neurons in a slice preparation of the isolated mouse IC. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun 10:1). After one week, auditory brainstem response (ABR) recordings and extracellular single-unit recordings from spontaneously active neurons within the IC slice were performed in noise-exposed and in normal hearing control mice. Noise-exposed animals showed a significant ABR threshold shift in the whole tested frequency range and a significant lower neuronal spontaneous activity in all investigated isofrequency laminae compared to controls. In both groups, the firing rate of 80% of IC neurons (approximately) increased significantly during the application of the GABA(A) receptor antagonist Bicucullin (10 microM). The present findings demonstrate a noise-related modulation of spontaneous activity in the IC, which possibly contribute to the generation of noise-induced tinnitus and hearing loss.     

Noise-induced cell death in the mouse medial geniculate body and primary auditory cortex

Noise-induced effects within the inner ear have been well investigated for several years. However, this peripheral damage cannot fully explain the audiological symptoms in noise-induced hearing loss (NIHL), e.g. tinnitus, recruitment, reduced speech intelligibility, hyperacusis. There are few reports on central noise effects. Noise can induce an apoptosis of neuronal tissue within the lower auditory pathway. Higher auditory structures (e.g. medial geniculate body, auditory cortex) are characterized by metabolic changes after noise exposure. However, little is known about the microstructural changes of the higher auditory pathway after noise exposure. The present paper was therefore aimed at investigating the cell density in the medial geniculate body (MGB) and the primary auditory cortex (AI) after noise exposure. Normal hearing mice were exposed to noise (10 kHz center frequency at 115 dB SPL for 3 h) at the age of 21 days under anesthesia (Ketamin/Rompun, 10:1). After 1 week, auditory brainstem response recordings (ABR) were performed in noise exposed and normal hearing animals. After fixation, the brain was microdissected and stained (Kluever-Barrera). The cell density in the MGB subdivisions and the AI were determined by counting the cells within a grid. Noise-exposed animals showed a significant ABR threshold shift over the whole frequency range. Cell density was significantly reduced in all subdivisions of the MGB and in layers IV-VI of AI. The present findings demonstrate a significant noise-induced change of the neuronal cytoarchitecture in central key areas of auditory processing. These changes could contribute to the complex psychoacoustic symptoms after NIHL.     

Noise-induced time-dependent changes in oxidative stress in the mouse cochlea and attenuation by D-methionine

Oxidative stress in the cochlea is considered to play an important role in noise-induced hearing loss. This study determined changes in superoxide dismutase (SOD), catalase, lipid peroxidation (LPO) and the auditory brainstem response (ABR) in the cochlea of C57BL/6 mice prior to and immediately, 1, 3, 7, 10, 14 and 21 days after noise exposure (4 kHz octave band at the intensity of 110 dB SPL for 4 h). A significant increase in SOD activity immediately and on 1st day after noise exposure, without a concomitant increase in catalase activity suggested a difference in the time dependent changes in the scavenging enzymes, which facilitates the increase in LPO observed on day 7. The ABR indicated significant noise-induced functional deficits which stabilized in 2 weeks with a permanent threshold shift (PTS) of 15 dB at both 4 kHz and 8 kHz. The antioxidant D-methionine (D-Met) reversed the noise-induced changes in LPO levels and enzyme activities. It also significantly reduced the PTS observed on the 14th day from 15 dB to 5 dB for 4 kHz. In summary, the findings indicate that time-dependent alterations in scavenging enzymes facilitate the production of reactive oxygen species and that D-met effectively attenuates noise-induced oxidative stress and the associated functional loss in the mouse cochlea.     

GFAP aggregates in the cochlear nerve increase the noise vulnerability of sensory cells in the organ of Corti in the murine model of Alexander disease

Outer hair cell (OHC) loss in the auditory sensory epithelium is a primary cause of noise-induced sensory-neural hearing loss (SNHL). To clarify the participation of glial cells in SNHL, we used an Alexander disease (AxD) mouse model. These transgenic mice harbor the AxD causal mutant of the human glial fibrillary acidic protein (GFAP) under the control of the mouse GFAP promoter. It is thought that GFAP aggregates compromise the function of astrocytes. In the auditory pathway, the formation of GFAP aggregates was observed only in GFAP-positive cells of the cochlear nerve. The presence of GFAP aggregates did not change auditory function at the threshold level. To assess the change in vulnerability to auditory excitotoxicity, both transgenic and control mice were treated with intense noise exposure. Auditory threshold shifts were assessed by auditory brainstem responses (ABR) at 1 and 4 weeks after noise exposure, and OHC damage was analyzed by quantitative histology at 4 weeks after exposure. Transgenic mice showed more severe ABR deficits and OHC damage, suggesting that cochlear nerve glial cells with GFAP aggregates play a role in noise susceptibility. Thus, we should focus more on the roles of cochlear nerve glial cells in SNHL.     

Noise-induced aspartate and glutamate efflux in the guinea pig cochlea and hearing loss

Aspartate and glutamate were monitored in the scala tympani of the guinea pig cochlea using in vivo microdialysis before and during noise exposure. Moderate level broad band noise [105 dB sound pressure level (SPL), 30 min] neither altered the levels of aspartate or glutamate, nor auditory brainstem response (ABR) thresholds. High level noise exposure (135 dB SPL, 30 min) caused a large increase in aspartate (330%), a smaller increase in glutamate (150%), and a permanent ABR threshold shift of 60-75 dB between 2.0 and 12.5 kHz. Morphological analysis of the cochlea revealed a collapse of supporting structures, swelling of the afferent dendrites under the inner hair cells, and outer hair cell loss. Pretreatment with the NMDA antagonist, MK 801 (1 mg/kg body weight, i.p.) 1 h before noise exposure protected the afferent dendrites from swelling but did not protect the collapse of supporting structures, outer hair cell loss, or auditory thresholds. In conclusion, the noise-induced increase in aspartate and glutamate release in the cochlea and the protective effect of NMDA antagonism suggest that these two neurotransmitters are involved in noise-induced hearing loss.     

Doxepin Mitigates Noise‐induced Neuronal Damage in Primary Auditory Cortex of Mice via Suppression of Acid Sphingomyelinase/Ceramide Pathway

Neuronal damage in primary auditory cortex (A1) underlies complex manifestations of noise exposure, prevention of which is critical for health maintenance. Acid sphingomyelinase (ASM) catalyzes generation of ceramide (Cer) which if over‐activated mediates neuronal disorders in various diseases. Tricyclic antidepressants (TCAs), by restraining ASM/Cer, benefits multiple neuronal anomalies, so we aimed to elucidate the effect of TCA on noise induced hearing loss and auditory cortex derangement, unraveling mechanism involved. The mice were exposed to noise with frequencies of 20–20 KHz and intensity of 95 dB. Doxepin hydrochloride (DOX), a kind of TCAs, was given intragastrically by 5 mg kg^?1 days^?1. Morphology of neurons was examined using hematoxylin‐eosin (HE) and Nissl staining. Apoptosis was assayed through transferase‐mediated dUTP nick end labeling (TUNEL). The content of ASM, Cer or acid ceramidase (AC) was detected by western blot and immunohistochemistry analysis. We demonstrated intense, broad band noise caused upward shift of auditory brainstem response (ABR) threshold to sound over frequencies 4–32 KHz, with prominent morphologic changes and enhanced apoptosis in neurons of primary auditory cortex (A1) (P < 0.05). DOX partly restored noise‐caused hearing loss alleviating morphologic changes or apoptosis remarkably (P < 0.05). Both ASM and Cer abundance were elevated significantly by noise which was reversed upon DOX treatment (P < 0.05), but neither noise nor DOX altered AC content. DOX had no influence on hearing, neuronal morphology or ASM/Cer in control mice. Our result suggests DOX palliates noise induced hearing loss and neuronal damage in auditory cortex by correcting over‐activation of ASM/Cer without hampering intrinsic behavior of it. Anat Rec, 300:2220–2232, 2017. © 2017 Wiley Periodicals, Inc.     

Upregulation of brain-derived neurotrophic factor and neuropeptide Y in the dorsal ascending sensory pathway following sciatic nerve injury in rat

The numerical density of calbindin D-28k and parvalbumin immunopositive neurons in the inferior colliculus (IC) in mice was increased after sound stimulation. An increased number of calbindin positive neurons was found in the deep layers of the external cortex (EC) and particularly in the dorsal cortex (DC) and commissural nucleus (NCO). An increase of parvalbumin positive neurons was found in the EC, central nucleus (ICC) and DC, but not in the NCO. The increased immunoreactivity related to sound exposure suggests the appearance of neurons which express these proteins after sound stimulation. The up-regulation of calcium-binding proteins in these neurons may be due to their protective role against overstimulation, their response to a higher auditory metabolic activity, or increasing effect of excitatory inputs after noise-induced hearing loss.     

Noise exposure-induced enhancement of auditory cortex response and changes in gene expression

Noise exposure is one of the most common causes of hearing loss. There is growing evidence suggesting that noise-induced peripheral hearing loss can also induce functional changes in the central auditory system. However, the physiological and biological changes in the central auditory system induced by noise exposure are poorly understood. To address these issues, neurophysiological recordings were made from the auditory cortex (AC) of awake rats using chronically implanted electrodes before and after acoustic overstimulation. In addition, focused gene microarrays and quantitative real-time polymerase chain reaction were used to identify changes in gene expression in the AC. Monaural noise exposure (120 dB sound pressure level, 1 h) significantly elevated hearing threshold on the exposed ear and induced a transient enhancement on the AC response amplitude 4 h after the noise exposure recorded from the unexposed ear. This increase of the cortical neural response amplitude was associated with an upregulation of genes encoding heat shock protein (HSP) 27 kDa and 70 kDa after several hours of the noise exposure. These results suggest that noise exposure can induce a fast physiological change in the AC which may be related to the changes of HSP expressions.     

Neuroprotective effects of T-817MA against noise-induced hearing loss

Oxidative stress, including reactive oxygen species and other free radicals, is thought to play an important role in neuronal cell death, including noise-induced hearing loss. 1-{3-[2-(1-Benzothiophen-5-yl)ethoxy]propyl}azetidin-3-ol maleate (T-817MA), a novel neurotrophic agent, protects against oxidative stress-induced neurotoxicity. This study examines the effects of T-817MA in noise-induced ototoxicity in the cochlea. Guinea pigs received treatment with T-817MA-enhanced water (0.2, 0.7 mg/ml) or untreated water (control) beginning 10 days prior to noise exposure and continuing through this study. All subjects were exposed to 4-kHz octave-band noise at 120-dB SPL for 5h. Auditory thresholds were assessed by sound-evoked auditory brainstem response at 4, 8, and 16kHz, prior to and 10 days following noise exposure. Hair cell damage was analyzed by quantitative histology. T-817MA significantly reduced threshold deficits and hair cell death. These results suggest T-817MA reduces noise-induced hearing loss and cochlear damage, suggesting functional and morphological protection.     

Ebselen prevents noise-induced excitotoxicity and temporary threshold shift

This investigation tested the hypothesis that a noise-induced temporary threshold shift (TTS) can be attenuated by a peroxynitrite scavenger, ebselen (2-phenyl-1,2-benzisoselenazol-3(2H)-one). Guinea pigs received an oral dose of the vehicle or 10 mg/kg ebselen 1 h before exposure to 115 dB SPL 4-kHz octave band noise for 3 h. In controls, auditory brainstem response (ABR) thresholds increased by 25–45 dB immediately after noise and returned to pre-exposure baseline thresholds 7 days later. Ebselen eliminated this ABR threshold shift following noise exposure. In controls, swelling of the afferent dendrites beneath the inner hair cells was evident immediately after noise, whereas ebselen significantly reduced this pathology. These findings suggest that scavenging peroxynitrite can attenuate noise-induced excitotoxicity and, thereby, TTS.     

Alleles that modulate late life hearing in genetically heterogeneous mice

A genetically heterogeneous population of mice was tested for hearing at 8, 18, and 22 months by auditory brainstem response (ABR), and genotyped at 128 markers to identify loci that modulate late life hearing loss. Half of the test mice were exposed to noise for 2 hours at age 20 months. Polymorphisms affecting hearing at 18 months were noted on chromosomes 2, 3, 7, 10, and 15. Most of these loci had effects only on responses to 48 kHz stimuli, but a subset also influenced the auditory brainstem response at lower frequencies. Loci on chromosomes 4, 10, 12, and 14 had significant effects on hearing at 22 months in noise-exposed mice, and loci on chromosomes 10 and 11 had effects on mice not exposed to noise. Outer hair cell loss was modulated by polymorphisms on chromosomes 10, 11, 12, 17, and 19. Resistance to age-related hearing loss is thus modulated by a set of genetic effects, some age-specific, some frequency specific, some dependent on prior exposure to noise, and some of which compromise survival of cochlear hair cells.     

Detection and differentiation of sensorineural hearing loss in mice using auditory steady-state responses and transient auditory brainstem responses

Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. We first characterized the ASSR evoked by sinusoidally amplitude-modulated tones in wild-type mice. ASSR were robustly elicited within three ranges of modulation frequencies below 200 Hz, from 200 to 600 Hz and beyond 600 Hz in most recordings. Using phase information we estimated the apparent ASSR latency to be about 3 ms, suggesting generation in the auditory brainstem. Auditory thresholds obtained by automated and visual analysis of ASSR recordings were comparable to those found with tone-burst evoked ABR in the same mice. We then recorded ASSR and ABR from mouse mutants bearing defects of either outer hair cell amplification (KCNQ4-knockout) or inner hair cell synaptic transmission (Bassoon-mutant). Both mutants showed an increase of ASSR and ABR thresholds of approximately 40 dB versus wild-type when investigated at 8 weeks of age. Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL.     

Up-regulation of cochlear Hes1 expression in response to noise exposure

Hes1, a hairy and enhancer of split homolog, negatively regulates inner ear hair cell differentiation. The main objective of this study was to investigate the status of the Hes1 gene in the noise-damaged cochlea in relation to the degree of noise-induced hearing loss (NIHL). Adult albino guinea pigs were exposed to white-band noise (115 dB sound pressure level). Noise exposure for either 1 or 3 hours induced significant elevations of threshold in auditory brainstem response (ABR) compared with unexposed controls. Succinate dehydrogenase staining showed that white-band noise exposure caused significant outer hair cell losses. In addition, we found significant up-regulations of cochlear Hes1 mRNA and protein expressions following acoustic trauma, and Hes1 mRNA expression was positively correlated with NIHL. These findings suggest that up-regulation of Hes1 expression in response to noise exposure may be one of the underlying mechanisms of NIHL.     

Group I metabotropic glutamate receptors in spiral ganglion neurons contribute to excitatory neurotransmissions in the cochlea

Evidence has accumulated over the years supporting glutamate as the primary neurotransmitter used by hair cells in afferent cochlear neurotransmission. Besides acting on ionotropic glutamate receptors, glutamate also activates second messenger systems via G-protein-coupled metabotropic glutamate receptors (mGluRs) to modulate neuronal excitability. However, it is unclear whether mGluRs participate in cochlear neurotransmission. We present evidence directly supporting a functional role for group I metabotropic glutamate receptors (mGluRIs) in spiral ganglion (SG) neurons. The presence of mGluRI and downstream G-protein subunits was demonstrated by molecular biology and immunolabeling methods. Direct activation of mGluRIs in cultured SG neurons resulted in transient increases of intracellular Ca(++) concentration and transient inward currents that gave rise to firings of multiple action potentials. These responses showed mGluRI pharmacological specificity and quickly desensitized. We next examined changes in cochlear function after noise exposure as a result of pharmacologically manipulating cochlear glutamate neurotransmission. These in vivo tests showed that blocking non-N-methyl-D-aspartic acid glutamate receptors was sufficient to eliminate compound action potentials of the auditory nerve, and pharmacologically inhibiting mGluRIs in the cochlea did not significantly affect the hearing threshold. In contrast, blocking mGluRIs lowered the amplitude of compound action potentials at louder sound levels and reduced the noise-induced temporary threshold shift. Our results suggest that although mGluRIs did not initiate fast excitatory cochlear neurotransmission, their activation contributed to the growth of excitatory responses of the cochlea. As a result, the cochlea was more resistant to noise-induced temporary hearing losses without the activation of mGluRIs in SG neurons.     

Limitation of Conventional Audiometry in Identifying Hidden Hearing Loss in Acute Noise Exposure

PurposeThe concept of hidden hearing loss can explain the discrepancy between a listener''s perception of hearing ability and hearing evaluation using pure tone audiograms. This study investigated the utility of the suprathreshold auditory brainstem response (ABR) for the evaluation of hidden hearing loss in noise-exposed ear with normal audiograms.Materials and MethodsA total of 15 patients (24 ears) with normal auditory thresholds and normal distortion product otoacoustic emissions were included in a retrospective analysis of medical records of 80 patients presenting with histories of acute noise exposure. The control group included 12 subjects (24 ears) with normal audiograms and no history of noise exposure. Pure tone audiometry and suprathreshold ABR testing at 90 dB peSPL were performed. The amplitudes and latencies of ABR waves I and V were compared between the noise-exposed and control groups.ResultsWe found no significant difference in the wave I or V amplitude, or the wave I/V ratio, between the two groups. The latencies of ABR wave I, V, and I-V interpeak interval were compared, and no significant intergroup difference was observed.ConclusionThe results suggest that either hidden hearing loss may not be significant in this cohort of patients with acute noise exposure history, or the possible damage by noise exposure is not reflected in the ABRs. Further studies are needed to inquire about the role of ABR in identification of hidden hearing loss.     

In vivo protective effect of ferulic acid against noise-induced hearing loss in the guinea-pig

Ferulic acid (FA) is a phenolic compound whose neuroprotective activity was extensively studied in vitro. In this study, we provided functional in vivo evidence that FA limits noise-induced hearing loss. Guinea-pigs exposed to acoustic trauma for 1 h exhibited a significant impairment in auditory function; this injury was evident as early as 1 day from noise exposure and persisted over 21 days. Ferulic acid (150 mg/kg i.p. for 4 days) counteracted noise-induced hearing loss at days 1, 3, 7 and 21 from noise exposure. The improvement of auditory function by FA was paralleled by a significant reduction in oxidative stress, apoptosis and increase in hair cell viability in the organ of Corti. Interestingly in the guinea-pig cochleae, the neuroprotective effect of FA was functionally related not only to its scavenging ability in the peri-traumatic period but also to the up-regulation of the cytoprotective enzyme heme oxygenase-1 (HO-1); in fact, FA-induced improvement of auditory function was counteracted by the HO inhibitor zinc-protoporphyrin-IX and paralleled the time-course of HO-1 induction over 3–7 days. These results confirm the antioxidant properties of FA as free-radical scavenger and suggest a role of HO-1 as an additional mediator against noise-induced ototoxicity.     

Moderate noise induced cognition impairment of mice and its underlying mechanisms

Noise pollution is recognized as a serious human health problem in modern society. The aim of the present study was to explore the effects of moderate-intensity white noise exposure on learning and memory of mice, and the underlying mechanisms. The learning and memory ability of mice were evaluated by water maze and step-down inhibitory avoidance experiments respectively, following 1, 3, and 6 weeks noise exposure (80 dB SPL, 2 h/day). To explore potential mechanisms, we determined levels of oxidative stress in the inferior colliculus (IC), auditory cortex (AC), and hippocampus (the structures comprising the critical encephalic region associated with the acoustic lemniscal ascending pathway), the phosphorylation of microtubule-associated protein tau in the hippocampus (important role in learning and memory), and the basic auditory response properties of neurons in the IC. Moderate-intensity noise exposure impaired the learning and memory ability of mice in both water maze and step-down inhibitory avoidance experiments, and the longer the noise exposure time the greater the impairment. At 6 weeks after noise exposure, there was also evidence of oxidative damage in the IC, AC, and hippocampus, hyperphosphorylated tau protein in the hippocampus, and significant changes in the auditory response properties of neurons in the IC. These data results suggest that moderate-intensity noise can progressively impair the learning and memory ability of mice, which may result from peroxidative damage, tau hyperphosphorylation, and auditory coding alteration.     

Membrane properties and firing patterns of inferior colliculus neurons: an in vivo patch-clamp study in rodents

The inferior colliculus (IC) is a large auditory nucleus in the midbrain, which is a nearly obligatory relay center for ascending auditory projections. We made in vivo whole cell patch-clamp recordings of IC cells in young-adult anesthetized C57/Bl6 mice and Wistar rats to characterize their membrane properties and spontaneous inputs. We observed spikelets in both rat (18%) and mouse (13%) IC neurons, suggesting that IC neurons may be connected by electrical synapses. In many cells, spontaneous postsynaptic potentials were sufficiently large to contribute to spike irregularity. Cells differed considerably in the number of simultaneous spontaneous postsynaptic potentials that would be needed to trigger an action potential. Depolarizing and hyperpolarizing current injections showed six different types of firing patterns: buildup, accelerating, burst-onset, burst-sustained, sustained, and accommodating. Their relative frequencies were similar in both species. In mice, about half of the cells showed a clear depolarizing sag, suggesting that they have the hyperpolarization-activated current I_h. This sag was observed more often in burst and in accommodating cells than in buildup, accelerating, or sustained neurons. Cells with I_h had a significantly more depolarized resting membrane potential. They were more likely to fire rebound spikes and generally showed long-lasting afterhyperpolarizations following long depolarizations. We therefore suggest a separate functional role for I_h.     

Inner hair cell ribbon synapse plasticity might be molecular basis of temporary hearing threshold shifts in mice

Recent studies have reported that noise exposure at relatively low intensities can cause temporary threshold shifts (TTS) in hearing. However, the mechanism underlying the TTS is still on debate. Here, we report that an acoustic stimulation (100 dB SPL, white noise) induced TTS in mice, with the maximal ABR threshold elevations seen on the 4^th day after noise exposure. On the other hand, there were no significant morphological changes in the cochlea. Further, there were paralleled changes of pre-synaptic ribbons in both the number and postsynaptic density (PSDs) during this noise exposure. The numbers of presynaptic ribbon, postsynaptic density (PSDs), and colocalized puncta correlated with the shifts of ABR thresholds. Moreover, a complete recovery of ABR thresholds and synaptic puncta was seen on the 14^th day after the noise stimulations. Thus, our study may indicate that noise exposure can cause a decline in cochlear ribbon synapses and result in consequent hearing loss. The reduction of synaptic puncta appears reversible and may contribute to hearing restoration in mice after noise exposure.     

Effects of salicylate on spontaneous activity in inferior colliculus brain slices

Salicylate is a well-known substance to produce reversible tinnitus in humans and animals. It has been shown that systemic application of salicylate changes the neuronal spontaneous activity in several parts of the auditory pathway. Salicylate has also a direct influence on cochlear outer hair cell electromotility. The effects observed in the central auditory structures in vivo could therefore be based upon the change in afferent cochlear input to the auditory system and in addition by a direct action of salicylate on neurons within the auditory pathway. The present study investigated the direct effect of salicylate application on the spontaneous activity of mouse inferior colliculus neurons in brain slices. Out of 92 neurons, 87% responded statistically significantly to the superfusate by changing their firing rates. 70% increased and 17% decreased their firing rates, respectively. Salicylate superfusion induced a general increase of electrophysiological activity within the inferior colliculus brain slice preparation which was similar to those obtained during systemic application of salicylate. The results suggest that the salicylate sensitivity of inferior colliculus neurons can modulate to a great extent the salicylate-induced generation of tinnitus.