Abstract:Tinnitus, the perception of a sound without an external acoustic source, is a complex perceptual phenomenon affecting the quality of life in 17% of the adult population. Despite its ubiquity and morbidity, the pathophysiology of tinnitus is a work in progress, and there is no generally accepted cure or treatment. Development of a reliable common animal model is crucial for tinnitus research and may advance this field. The goal of this study was to develop a tinnitus mouse model. Tinnitus was induced in an expe… Show more
“…Control mice were also monitored within the same time period. To demonstrate the development of tinnitus over a 360 day period in the same group of mice, Figures
1,
2,
3,
4 and
5 include some figures from Longenecker and Galazyuk
2011 showing data up to the 84 day time point.Figure 1
Fluctuations of gap-induced suppression of the acoustic startle response over a 360 day period in a control mouse. Open bars represent control means ± SD of (G + S)/S ratios measured at 6 different background frequencies (10, 12.5, 16, 20, 25, and 31.5 kHz).…”
Tinnitus is a maladaptive neuropathic condition that develops in humans and laboratory animals following auditory insult. In our previous study we demonstrated that sound exposure leads to development of behavioral evidence of tinnitus in a sample of exposed mice. However, this tinnitus mouse model did not account for long-term maladaptive plasticity or aging, factors that are commonly linked to the human tinnitus population. Therefore the same group of mice was monitored for tinnitus for 360 days post exposure. Tinnitus was assessed behaviorally by measuring gap-induced pre-pulse suppression of the acoustic startle (GPIAS). Cochlear histology was performed on both control (unexposed) and experimental mice to determine whether sound exposure caused any evident cochlear damage. We found that 360 days after exposure the vast majority of exposed mice exhibited similar gap detection deficits as detected at 84 days post exposure. These mice did not demonstrate significant loss of inner/outer hair cells or spiral ganglion neurons compared to the control sample. Lastly, we demonstrated that GPIAS deficits observed in exposed animals were unlikely exclusively caused by cochlear damage, but could be a result of central auditory maladaptive plasticity. We conclude that CBA/CaJ mice can be considered a good animal model to study the possible contribution of age effects on tinnitus development following auditory insult.
“…Control mice were also monitored within the same time period. To demonstrate the development of tinnitus over a 360 day period in the same group of mice, Figures
1,
2,
3,
4 and
5 include some figures from Longenecker and Galazyuk
2011 showing data up to the 84 day time point.Figure 1
Fluctuations of gap-induced suppression of the acoustic startle response over a 360 day period in a control mouse. Open bars represent control means ± SD of (G + S)/S ratios measured at 6 different background frequencies (10, 12.5, 16, 20, 25, and 31.5 kHz).…”
Tinnitus is a maladaptive neuropathic condition that develops in humans and laboratory animals following auditory insult. In our previous study we demonstrated that sound exposure leads to development of behavioral evidence of tinnitus in a sample of exposed mice. However, this tinnitus mouse model did not account for long-term maladaptive plasticity or aging, factors that are commonly linked to the human tinnitus population. Therefore the same group of mice was monitored for tinnitus for 360 days post exposure. Tinnitus was assessed behaviorally by measuring gap-induced pre-pulse suppression of the acoustic startle (GPIAS). Cochlear histology was performed on both control (unexposed) and experimental mice to determine whether sound exposure caused any evident cochlear damage. We found that 360 days after exposure the vast majority of exposed mice exhibited similar gap detection deficits as detected at 84 days post exposure. These mice did not demonstrate significant loss of inner/outer hair cells or spiral ganglion neurons compared to the control sample. Lastly, we demonstrated that GPIAS deficits observed in exposed animals were unlikely exclusively caused by cochlear damage, but could be a result of central auditory maladaptive plasticity. We conclude that CBA/CaJ mice can be considered a good animal model to study the possible contribution of age effects on tinnitus development following auditory insult.
“…8, insets) will be less detectable if the perceived tinnitus has characteristics of the carrier and "fills" the gap. Gap PPI can be reduced in noise-exposed animals compared with control animals for narrowband carriers centered at some frequencies but not others (see, e.g., Longenecker and Galazyuk 2011), in which case the animals are hypothesized to have spectrally restricted tinnitus.…”
Section: Prepulse Inhibition (Ppi) Of the Acoustic Startle Is Enhanmentioning
Here we ask whether this noise-induced primary neuronal degeneration results in abnormal auditory behavior, based on the acoustic startle response (ASR) and prepulse inhibition (PPI) of startle. Responses were measured in mice exposed either to a "neuropathic" noise or to a lower-intensity, "nonneuropathic" noise and in unexposed control mice. Mice with cochlear neuropathy displayed hyperresponsivity to sound, evidenced by enhanced ASR and PPI, while exposed mice without neuronal loss showed controllike responses. Gap PPI tests, often used to assess tinnitus, revealed limited gap detection deficits in mice with cochlear neuropathy only for certain gap-startle latencies, inconsistent with the presence of tinnitus "filling in the gap." Despite significantly reduced wave 1 of the auditory brainstem response, representing cochlear nerve activity, later peaks were unchanged or enhanced, suggesting compensatory neural hyperactivity in the auditory brainstem. Considering the rapid postexposure onset of both cochlear neuropathy and exaggerated startle-based behavior, the results suggest a role for cochlear primary neuronal degeneration, per se, in the central neural excitability that could underlie the generation of hyperacusis. acoustic startle response; prepulse inhibition; auditory brainstem response; noise-induced hearing loss; acoustic trauma
“…Ideally, even the time of exposure should be standardized in light of evidence that cochlear noise vulnerability appears subject to a diurnal cycle (Meltser et al 2014). In some studies, the goal may be unilateral NIPTS, so that an anesthetized animal may be positioned to only expose one ear (e.g., Longenecker and Galazyuk 2011;Turner et al 2012;Hickox and Liberman 2014). If the goal is explicitly to study unilateral NIPTS, this may be reasonable.…”
Section: Unilateral Noise Exposure and Anesthesiamentioning
Laboratory mice (Mus musculus) have become the major model species for inner ear research. The major uses of mice include gene discovery, characterization, and confirmation. Every application of mice is founded on assumptions about what mice represent and how the information gained may be generalized. A host of successes support the continued use of mice to understand hearing and balance. Depending on the research question, however, some mouse models and research designs will be more appropriate than others. Here, we recount some of the history and successes of the use of mice in hearing and vestibular studies and offer guidelines to those considering how to apply mouse models.
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