Auditory neuropathy is a kind of deafness in which cochlear outer hair cells function normally, but the auditory nerve fibers and/or the inner hair cells they innervate are dysfunctional. Clinically, this is identified by normal otoacoustic emissions but an absent or grossly abnormal auditory brainstem response. Some patients with auditory neuropathy have normal hearing thresholds but extreme difficulty understanding speech and hearing in noise. The threshold of the middle-ear muscle reflex (MEMR) is often elevated or immeasurable in these patients, as well. Recent work from the Liberman lab has suggested that observation of normal hearing thresholds with concomitant hearing-in-noise deficits can be explained by the degeneration of a specific subtype of cochlear nerve fibers with low spontaneous rates (SR) and high thresholds. This phenotype can be induced in laboratory animals with overexposure to loud sounds that causes only transient threshold elevation. I have assessed the MEMR in mice by measuring suppression of distortion-product otoacoustic emissions (DPOAEs) by contralateral sound before and after systemic application of curare, which blocks synaptic transmission at neuromuscular junctions. My preliminary data suggest that DPOAE suppression by contralateral sound is dominated by the MEMR, and my data substantiate the hypothesis that low-SR fibers dominate the drive to the MEMR, specifically that provided by the stapedial reflex. Here, I propose to design a test for MEMR measurements in mice that is more similar to that used in humans and subsequently use this test to compare MEMR thresholds, growth functions, and maximum suppression in low-SR neuropathic vs. control mice. This will allow me to more rigorously test the hypothesis that the MEMR is driven by low-SR auditory nerve fibers, and that as such, the MEMR can be used as a sensitive clinical test to identify low-SR cochlear neuropathy. The availability of an early diagnostic tool is of utmost importance: because one role of the MEMR is to protect the inner ear from high-level sound, low-SR cochlear neuropathy can lead to a vicious cycle wherein the ear becomes more damaged as its protective mechanisms deteriorate. Potential treatments for some types of auditory neuropathy are on the horizon, but to treat this pathology, we must first be able to identify it. The experiments in this proposal aim to improve the diagnostic utility of the MEMR in cochlear neuropathy that is specific to low-SR cochlear nerve fibers.
Our understanding of primary auditory neuropathy, the pathological condition in which cochlear nerve fibers degenerate despite the presence of healthy receptor cells in the cochlea, has improved dramatically in the past 20 years. However, there remain types of auditory neuropathy that are difficult to diagnose, such as that which affects only fibers with normally high thresholds that are thought to be critical to hearing in noise, and indeed, the death of these cochlear nerve fibers is observed in both noise-induced and age-related hearing loss. The proposed work aims to test the long-standing hypothesis that the middle-ear muscle reflex is driven by these high-threshold neurons and therefore that this reflex may serve as a useful diagnostic tool.
| Valero, M D; Burton, J A; Hauser, S N et al. (2017) Noise-induced cochlear synaptopathy in rhesus monkeys (Macaca mulatta). Hear Res 353:213-223 |
| Valero, Michelle D; Hancock, Kenneth E; Liberman, M Charles (2016) The middle ear muscle reflex in the diagnosis of cochlear neuropathy. Hear Res 332:29-38 |
