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

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 stimulus-specific 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

Ameliorative Effects of Exposing DBA/2J Mice to an Augmented Acoustic Environment on Histological Changes in the Cochlea and Anteroventral Cochlear Nucleus

DBA/2J (D2) mice, which exhibit very early progressive sensorineural hearing loss, were treated nightly with an augmented acoustic environment (AAE) initiated before the onset of hearing, and consisting of repetitive bursts of a 70-dB sound pressure level (SPL), 4–25 kHz noise band. At 55 days of age, AAE-treated mice exhibited less elevation of auditory brainstem response thresholds, fewer missing hair cells, and greatly reduced loss of anteroventral cochlear nucleus (AVCN) volume and neuron number compared to untreated control mice. It was hypothesized that the central neuroprotective effect was associated with increased afferent input to AVCN neurons evoked by the AAE as well as a healthier cochlea

Gravity Receptor Aging in the CBA/CaJ Strain: A Comparison to Auditory Aging

The CBA/CaJ mouse strain is commonly used as a control as it has no known genetic mutations affecting the inner ear, maintains hearing sensitivity throughout life, and serves as a background for creating new genetic strains. The purpose of the present study was to characterize the effects of age and gender on gravity receptor function and compare functional changes between auditory and vestibular modalities. Vestibular-evoked potentials (VsEPs), auditory brainstem responses (ABRs), and distortion product otoacoustic emissions were measured in 131 mice. VsEP thresholds deteriorated an average of 0.39 dB re: 1.0 g/ms per month and at the oldest ages (18–23 months old) showed an average loss of 49% of VsEP dynamic range. No significant gender differences were found for VsEPs. ABR thresholds increased by an average of 1.35, 1.38, and 1.15 dB pe SPL per month for ABR stimulus frequencies of 8, 16, and 32 kHz, respectively, demonstrating an average decrease in auditory dynamic range of 25–35% at advanced ages. Both modalities declined with age. Age-related decreases in gravity receptor sensitivity should be considered when using the CBA/CaJ strain for vestibular studies

Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae

Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as ‘good hearing’ standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70–83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (∼18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or ‘root’ cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis