DECIPHERING THE MECHANISMS UNDERLYING AUDITORY HYPEREXCITABILITY IN TWO GENETIC MOUSE MODELS SUSCEPTIBLE TO AUDIOGENIC SEIZURES

An exquisite characteristic of the auditory system is its ability to sense a large range of sound intensities from whispers to loud alarm sounds, covering 6 orders of magnitude in acoustic pressure. Deficits of sound intensity processing may lead to hearing loss and/or major auditory perception distortions like tinnitus, the perception of phantom sounds, or hyperacusis, a reduced tolerance for moderate sound levels. Audiogenic seizures, reflex seizures induced by loud sounds, are a common feature of many mouse models for central nervous system disorders and may be seen as a model of auditory hyperexcitability. However, the mechanisms underlying these seizures are still poorly understood. Interestingly both peripheral and central hearing impairments, either acquired or congenital, increase the susceptibility to these seizures. Here, we report two genetic mouse models for deafness, which show a particularly high and sustainable susceptibility over development to audiogenic seizures. Through the creation of the corresponding cre fate mapping tools, we identified and characterized two candidate neuronal populations in the auditory brainstem with functional deficits, and explored their connectivity in the cochlear nucleus, which could account for auditory hyperexcitability in these genetic forms of deafness. These models provide new opportunities for deciphering pathophysiological mechanisms of auditory hyperexcitability.