Effects of cochlear synaptopathy on middle-ear muscle reflexes in unanesthetized mice

• Published in: Hearing research Vol. 363; pp. 109 - 118
• Main Authors: Valero, Michelle D., Hancock, Kenneth E., Maison, Stéphane F., Liberman, M. Charles
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-06-2018
• Subjects: Acoustic overexposure; Acoustic Stimulation; Animals; Auditory Threshold; Cochlea - metabolism; Cochlea - physiopathology; Cochlear Diseases - genetics; Cochlear Diseases - metabolism; Cochlear Diseases - physiopathology; Cochlear Diseases - psychology; Cochlear Nerve - metabolism; Cochlear Nerve - physiopathology; Cochlear synaptopathy; Disease Models, Animal; Evoked Potentials, Auditory, Brain Stem; Hearing Loss, Sensorineural - genetics; Hearing Loss, Sensorineural - metabolism; Hearing Loss, Sensorineural - physiopathology; Hearing Loss, Sensorineural - psychology; Hidden hearing loss; Mice, Inbred CBA; Mice, Knockout; Middle-ear muscle reflex; Muscle Contraction; Nerve Degeneration; Receptors, Nicotinic - genetics; Reflex, Acoustic; Stapedius - innervation; Synapses; Wideband reflex; Cochlear synaptopathy; Middle-ear muscle reflex; Acoustic overexposure; Hidden hearing loss; Wideband reflex
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2018.03.012

Cochlear synaptopathy, i.e. the loss of auditory-nerve connections with cochlear hair cells, is seen in aging, noise damage, and other types of acquired sensorineural hearing loss. Because the subset of auditory-nerve fibers with high thresholds and low spontaneous rates (SRs) is disproportionately affected, audiometric thresholds are relatively insensitive to this primary neural degeneration. Although suprathreshold amplitudes of wave I of the auditory brainstem response (ABR) are attenuated in synaptopathic mice, there is not yet a robust diagnostic in humans. The middle-ear muscle reflex (MEMR) might be a sensitive metric (Valero et al., 2016), because low-SR fibers may be important drivers of the MEMR (Liberman and Kiang, 1984; Kobler et al., 1992). Here, to test the hypothesis that narrowband reflex elicitors can identify synaptopathic cochlear regions, we measured reflex growth functions in unanesthetized mice with varying degrees of noise-induced synaptopathy and in unexposed controls. To separate effects of the MEMR from those of the medial olivocochlear reflex, the other sound-evoked cochlear feedback loop, we used a mutant mouse strain with deletion of the acetylcholine receptor required for olivocochlear function. We demonstrate that the MEMR is normal when activated from non-synaptopathic cochlear regions, is greatly weakened in synaptopathic regions, and is a more sensitive indicator of moderate synaptopathy than the suprathreshold amplitude of ABR wave I.
Cochlear synaptopathy is a significant problem in sensorineural hearing lossSynaptopathy has no definitive diagnostic test in humansThe middle-ear muscle reflex (MEMR) could be a sensitive metric of synaptopathyThe MEMR in mouse can identify cochlear synaptopathic regions with octave-band resolutionThe MEMR may be useful in estimating the severity of synaptopathy