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.
Ison
James R
JR
Department of Brain and Cognitive Sciences, University of Rochester, Meliora Hall, Rochester, NY 14627, USA. JIson@bcs.rochester.edu
Allen
Paul D
PD
O'Neill
William E
WE
D000375:Aging / Q000502:physiology*; D000818:Animals; D001309:Auditory Threshold; D016057:Evoked Potentials, Auditory, Brain Stem; D005260:Female; D034381:Hearing Loss / Q000503:physiopathology*; D012001:Hyperacusis / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D012018:Reflex / Q000502:physiology*; D013216:Reflex, Startle / Q000502:physiology*; D012044:Regression Analysis