Effect of Selective Ototoxicity and Noise Exposure on the Middle Ear Muscle Reflex in Chinchilla

Inner and outer hair cells (IHC and OHC, respectively) are the two primary sensory cell types in the mammalian cochlea. Despite extensive IHC innervation by auditory afferent nerve fibers (ANF), our understanding of the role of IHC on daily listening ability is limited. Over 90% of ANF activity arises from IHC activation; however, some auditory tasks appear unaffected by extensive IHC loss. For example, significant IHC loss has little-to-no impact on hearing thresholds across frequencies in the audiogram, the universal test of hearing sensitivity, but significantly degrades tone-in-noise detection. This suggests that IHCs play a crucial role in complex auditory tasks that are not well evaluated in routine clinical tests of hearing. Considering the emphasis on the audiogram as a basis for treatment and rehabilitation of individuals with hearing loss, the lack of sensitivity to IHC pathology is particularly concerning. Previous reports have proposed that the middle ear muscle reflex (MEMR) may serve as a sensitive diagnostic test for subclinical hearing loss. Cochlear synaptopathy (CS), believed to be a form of subclinical hearing loss, is characterized by loss of presynaptic IHC ribbon synapses following noise exposure or aging. CS symptoms are speculated to include normal audiometry, poorer-than-expected hearing-in-noise ability, and an increased probability of experiencing tinnitus or hyperacusis. Data from human studies have suggested that CS may be the underlying pathology in individuals with normal hearing sensitivity who report disproportionately poorer hearing-in-noise ability, and that CS and other forms of IHC pathology may be detectable using the MEMR. The MEMR is an involuntary contraction of the middle ear stapedius muscle that decreases the admittance of the tympanic membrane to attenuate loud acoustic signals, via a reflex loop that is initiated by IHC transmitter release and ANF discharge. MEMR threshold and amplitude measures can provide information regarding the integrity of a patient’s peripheral and central auditory system. In clinical practice, MEMR threshold and amplitude are routinely assessed as part of a standard audiological diagnostic test battery. The MEMR has recently been suggested to be a sensitive measure of CS when measured with a wideband probe, and not the standard clinical single-frequency probe. Previous data has shown that MEMR thresholds measured using a 226 Hz probe tone were unaffected by severe and selective loss of IHC in chinchillas treated with carboplatin, an anticancer drug that destroys IHC in this species. To explore potential differences among MEMR probes on the effect of selective IHC loss, the MEMR was measured using both a wideband probe and a single-frequency probe in chinchillas with moderate to severe IHC loss. To explore potential differences among MEMR probes on the effect of IHC synapse loss and selective IHC loss, this dissertation measured responses related to the MEMR before and after two cochlear lesion models in the chinchilla: (1) noise-induced IHC synaptopathic damage and (2) carboplatin-induced selective IHC loss. The proposed study will gauge the sensitivity of the MEMR to hair cell pathology and could advance our understanding of the mechanisms that generate the MEMR.