Age-Related Hearing Loss in C57BL/6J Mice has both Frequency-Specific and Non-Frequency-Specific Components that Produce a Hyperacusis-Like Exaggeration of the Acoustic Startle Reflex

Abstract

Auditory brainstem-evoked response (ABR) thresholds were obtained in a longitudinal study of C57BL/6J mice between 10 and 53 weeks old, with repeated testing every 2 weeks. On alternate weeks, acoustic startle reflex (ASR) amplitudes were measured, elicited by tone pips with stimulus frequencies of 3, 6, 12, and 24 kHz, and intensities from subthreshold up to 110 dB sound pressure level. The increase in ABR thresholds for 3 and 6 kHz test stimuli followed a linear time course with increasing age from 10 to 53 weeks, with a slope of about 0.7 dB/week, and for 48 kHz a second linear time course, but beginning at 10 weeks with a slope of about 2.3 dB/week. ABR thresholds for 12, 24, and 32 kHz increased after one linear segment with a 0.7 dB slope, then after a variable delay related to the test frequency, shifted to a second segment having slopes of 3-5 dB/week. Hearing loss initially reduced the ASR for all eliciting stimuli, but at about 6 months of age, the response elicited by intense 3 and 6 kHz stimuli began to increase to reach values about three times above normal, and previously subthreshold stimuli came to elicit vigorous responses seen at first only for the intense stimuli. This hyperacusis-like effect appeared in all mice but was especially pronounced in mice with more serious hearing loss. These ABR data, together with a review of histopathological data in the C57BL/6 literature, suggest that the non-frequency-specific slow time course of hearing loss results from pathology in the lateral wall of the cochlea, whereas the stimulusspecific hearing loss with a rapid time course results from hair cell loss. Delayed exaggeration of the ASR with hearing loss reveals a deficit in centrifugal inhibitory control over the afferent reflex pathways after central neural reorganization, suggesting that this mouse may provide a useful model of age-related tinnitus and associated hyperacusis.

The Medial Olivocochlear System Attenuates the Developmental Impact of Early Noise Exposure

“…Linear regressions (implemented in MATLAB using the regress function) found statistically significant correlations (PG0.05) between relative ASR and 8-kHz thresholds at lead times of 1 and 2 ms. As previously noted (Ison et al 2007), these results suggest that the exaggerated ASR at short lead times is a manifestation of a hyperacusis-like phenomenon in mice with hearing loss. Despite the statistical significance of this relationship, affected mice in the present study showed modest threshold shifts (∼10 dB) relative to FIG.…”

“…3B) was the potentiated startle response at a lead time of 1 ms. This exaggeration of the startle response has been previously described in older C57BL/6 J mice (Ison et al 2007). Because the effect came at a later age relative to the age-related loss of cochlear hair cells, it has been attributed to a reorganization of the central afferent pathways that follows the disruption of peripheral inputs.…”

Early Postnatal Development of Spontaneous and Acoustically Evoked Discharge Activity of Principal Cells of the Medial Nucleus of the Trapezoid Body: AnIn VivoStudy in Mice

“…CBA/J mice are known for their persistent hearing sensitivity while C57BL/6J mice suffer from an early onset of high-frequency hearing loss so far reported to start at 2 months of age (Mikaelian, 1979;Henry and Chole, 1980;Li and Borg, 1991;Henry, 2004;Ison et al, 2007) The present data suggest that the deterioration of hearing sensitivity in C57BL/6J mice might even begin at the end of the first postnatal month. Except for threshold values, we did not find any major indications for strain-specific differences in spontaneous and acoustically evoked discharge characteristics of MNTB units.…”

Assessment of Synaptic Plasticity via Long-Term Potentiation in Young Mice on the Day after Acoustic Trauma: Implications for Tinnitus

“…These two methods have already been described in detail in the literature. As generally accepted, the magnitude and peak latency of the SR response are the basic parameters of this method [10,11] . In this study, SRT was used to determine the subjective auditory threshold of the mice, and GDT was employed to detect tinnitus induction.…”