In the cochlea, afferent transmission between inner hair cells and auditory neurons is mediated by glutamate receptors. Glutamate transporters located near the synapse and in spiral ganglion neurons are thought to maintain low synaptic levels of glutamate. We analyzed three glutamate transporter blockers for their ability to alter the effects of glutamate, exogenously applied to the synapse via perfusion of the scala tympani of the mouse, and compared that action to their ability to alter the effects of intense acoustic stimulation. Threo-beta-benzyloxyaspartate (TBOA) is a broad-spectrum glutamate transporter antagonist, affecting all three transporters [glutamate/aspartate transporter (GLAST), glutamate transporter-1 (GLT1), and excitatory amino acid carrier 1 (EAAC1)]. l-serine- O-sulfate (SOS) blocks both GLAST and EAAC1 without effect on GLT1. Dihydrokainate (DHK) is selective for GLT1. Infusion of glutamate (10 μM for 220 min), TBOA (200 μM for 220 min), or SOS (100 μM for 180 min) alone did not alter auditory neural thresholds. When infused together with glutamate, TBOA and SOS produced significant neural threshold shifts, leaving otoacoustic emissions intact. In addition, both TBOA and SOS exacerbated noise-induced hearing loss by producing larger neural threshold shifts and delaying recovery. DHK did not alter glutamate- or noise-induced hearing loss. The evidence points to a major role for GLAST, both in protecting the synapse from exposure to excess extracellular glutamate and in attenuating hearing loss due to acoustic overstimulation.
TrkB agonist drugs are shown here to have a significant effect on the regeneration of afferent cochlear synapses after noise-induced synaptopathy. The effects were consistent with regeneration of cochlear synapses that we observed in vitro after synaptic loss due to kainic acid-induced glutamate toxicity and were elicited by administration of TrkB agonists, amitriptyline, and 7,8-dihydroxyflavone, directly into the cochlea via the posterior semicircular canal 48 hours after exposure to noise. Synaptic counts at the inner hair cell and wave 1 amplitudes in the auditory brainstem response (ABR) were partially restored 2 weeks after drug treatment. Effects of amitriptyline on wave 1 amplitude and afferent auditory synapse numbers in noise-exposed ears after systemic (as opposed to local) delivery were profound and long-lasting; synapses in the treated animals remained intact 1 year after the treatment. However, the effect of systemically delivered amitriptyline on synaptic rescue was dependent on dose and the time window of administration: it was only effective when given before noise exposure at the highest injected dose. The long-lasting effect and the efficacy of postexposure treatment indicate a potential broad application for the treatment of synaptopathy, which often goes undetected until well after the original damaging exposures.
Noise-induced hearing loss (NIHL) and age-related hearing loss (AHL, or presbycusis) are widespread health problems that will continue to increase as our society ages. NIHL and AHL often coexist in the same ear; however, the conditions under which they interact and the mechanisms by which they do so remain poorly understood. Inspired by epidemiological studies suggesting that noise-exposed ears age differently from nonexposed ears [Gates et al., ‘‘Logitudinal threshhold changes in people with audiometric notches,’’ Hear. Res. 141, 220–228 (2000)], we studied interactions between NIHL and AHL in mouse; an animal with a short life span, with intrastrain genetic homogeneity to minimize variability and with interstrain differences in vulnerability which can be exploited to probe mechanisms. Using such models, we have uncovered evidence that early noise exposure can have an ongoing influence on the nature and progression of an age-related hearing loss. The nature of this age-related hearing loss exacerbation is special; it can occur even in ears without permanent threshold shifts from the noise and leads to massive loss of spiral ganglion neurons despite intact hair cell populations. Findings have practical importance for investigations of NIHL in animal models, and may have implications for clinical practices allocating noise-induced and age-related components of hearing loss as strictly additive. [Work supported by NIH.]
Context: Sound levels in fitness classes often exceed safe levels despite studies that show many participants find high sound levels stressful. Aims: The objective is to determine if lower sound levels in spinning classes significantly impact exercise intensity and to determine if class participants prefer the music played at lower levels. Settings and Design: Observational study of 1-hour group spin classes. Methods and Materials: Sound levels were measured in 18 spin classes over two weeks. No adjustments were made in week-1 and sound levels were decreased by 3 dB in week-2. Participant preferences and data on post-class hearing changes were collected via post-class questionnaires ( n = 213) and divided into three terciles based on the total sound exposure of corresponding classes. Statistical Analysis Used: Unweighted survey generalized linear models are used to sort the causal relationships between different variables simultaneously and participant responses. The Chi-square test is used to reveal statistically significant relationships between two or more categorical variables. Results: When mean sound levels exceeded 98.4 dBC, respondents were 23 times more likely to report the music as too loud than too quiet ( P < 0.05), and four times more likely to prefer a decrease, rather than an increase, in sound level ( P < 0.05). There was no significant difference in respondents reporting high exercise intensity between the middle (95.7–98.1 dBC) and upper (98.4–101.0 dBC) terciles, 67.1% and 71.8%, respectively ( P = 0.53). Overall, 25.9% of respondents reported auditory symptoms following classes. Analysis in the context of dBA and dBC produced congruent conclusions and interpretations. Conclusions: Sound levels in many fitness classes remain dangerously high. However, music level can be lowered without a significant impact on perceived exercise intensity and many participants prefer lower sound levels than current levels.
Brown, M. C, S. G. Kujawa, and M. C. Liberman. Single olivocochlear neurons in the guinea pig. II. Response plasticity due to noise conditioning. J. Neurophysiol. 79: 3088–3097, 1998. Previous studies have shown that daily, moderate-level sound exposure, or conditioning, can reduce injury from a subsequent high-level noise exposure. We tested the hypothesis that this conditioning produces an increased activity in the olivocochlear efferent reflex, a reflex known to provide protection to the cochlea. Guinea pigs were conditioned by a 10-day intermittent exposure to 2–4 kHz noise at 85 dB sound pressure level. This conditioning is known to reduce damage from a subsequent high-level exposure to the same noise band. Responses to monaural and binaural sound were recorded from single medial olivocochlear (MOC) efferent neurons, and data from conditioned animals were compared with those obtained from unexposed controls. MOC neurons were classified by their response to noise bursts in the ipsilateral or contralateral ears as ipsi units, contra units, or either-ear units. There were no significant differences in the distributions of these unit types between control and conditioned animals. There were also no differences in other responses to monaural stimuli, including the distribution of characteristic frequencies (CFs), the sharpness of tuning, or thresholds at the CF. For binaural sound at high levels, particularly relevant to sound-evoked activation of the MOC reflex during acoustic overstimulation, the firing rates of MOC neurons with CFs just above the conditioning band showed slight (but statistically significant) elevations relative to control animals. Frequency regions just above the conditioning band also demonstrated maximum conditioning-related protection; thus protection could be due, in part, to long-term changes in MOC discharge rates. For binaural sound at low levels, MOC firing rates in conditioned animals also were increased significantly relative to controls. Again, increases were largest for neurons with CFs just above the conditioning band. For equivalent monaural sound, rates were not significantly increased; thus, conditioning appears to increase binaural facilitation by opposite-ear sound. These data indicate that MOC neurons show long-term plasticity in acoustic responsiveness that is dependent on their acoustic history.
