A mouse model of the auditory nerve to study cochlear synaptopathy

Several non-human animal studies have demonstrated a permanent loss of auditory nerve (AN) fiber synapses after noise over-exposure, termed cochlear synaptopathy, without causing hair cell loss nor altering normal auditory thresholds (e.g., Kujawa and Liberman, 2009). Studies in human listeners are generally inconclusive, mainly because assessing the status of the AN in humans represents a major challenge. In a previous study, we proposed the use of envelope following responses (EFR) as a tool to investigate synaptopathy both in mice and humans (Encina-Llamas et al., under review; Parthasarathy et al., 2017). Similar patterns in synaptopathic mice and humans were found. The use of a "humanized" version of the AN model by Zilany et al. (2009, 2014) could qualitatively account for the patterns obtained in the human listeners. Nevertheless, the use of the original animal version of the AN model (based on the cat) failed to simulate EFRs in mice. It was argued that a species-specific AN model could improve the non-human animal simulations. Given that the mouse is the most used and best characterized species in connection with cochlear synaptopathy, the present study proposes a modification of the original AN model by Zilany et al. (2009, 2014) based on cat data adapted to the mouse