NT3 treatment for brain coding restoration after cochlear synaptopathy
Royal National Institute for Deaf People
University of Michigan Health System
After noise-exposure that produces TTS, and thus clinically ‘normal’ audiograms, there is nonetheless permanent damage to auditory nerve (AN) - hair-cell synapses. 'Hidden' hearing loss is a potential major health issue, as temporal bone and ABR studies suggest it is common in humans, causing difficulties understanding speech in noise. These deficits reflect temporal-coding problems likely due to loss of high-threshold, low-spontaneous rate ANFs, which are preferentially affected after TTS. The primary central targets of high-threshold ANFs reside in the small cell cap (SCC) of the cochlear nucleus (CN), which is prominent in humans. SCC neurons display large dynamic ranges and superior suprathreshold tuning and temporal coding, which are essential for speech perception in noisy environments. The SCC is a recipient and projection area of medial olivocochlear (MOC) neurons which minimize threshold shifts after noise damage, and thus likely also play a role in SCC circuits in hidden hearing loss. The overall hypothesis of this proposal is that the SCC plays a major role in suprathreshold sound coding and that this coding is highly susceptible to degradation by hidden hearing loss. We will elucidate the cochlea-SCC-MOC circuit in normal and noise-damaged animals with hidden hearing loss, using optogenetics, physiology and tract tracing. Furthermore, we will determine whether NT3 restoration of ANFs affects auditory processing in the SCC after noise damage. Cochlear delivery of neurotrophins in humans is easily achieved via trans-tympanic injections, suggesting a possible clinical intervention.
2.1 Biological and endogenous factors