Cochlear Implant Recordings from Deafened DTR Mice: Where Neurons Survive Despite Loss of Hair Cells

A limitation of many animal models for cochlear implant (CI) is that the condition of the auditory nerve is closely tied to hair cell (HC) survival, so it is difficult to determine which of these elements contributes directly to the functional responses to electrical stimulation. We adopted the diphtheria toxin receptor (DTR) mouse as a novel candidate for CI research and developed a chronically-implanted DTR mouse model. Following diphtheria toxin
(DT) injection, these mice exhibit robust AN survival despite complete HC depletion. DTR mice treated with DT and wild type (WT) control mice were implanted with a single platinum/iridium ball electrode in the scala tympani and tested for up to 70 days. Electrically-evoked auditory brainstem responses (EABRs) recorded under anesthesia were obtained to assess differences in evoked neural activity and changes over time after implantation. EABR amplitude growth functions (neural response magnitude vs stimulus current level) for deafened DTR mice were similar to WT mice. Preliminary histology confirmed loss of HCs and showed a correlation between neuronal survival and EABRs. Based on results to date, the chronically implanted DTR mouse is a promising model for investigating the effects of HC and AN survival on CI function. The successful implantation and recording also suggest that mutant deafness mice modeling human hereditary hearing loss can be used for research on outcomes of CI in specific genetic diseases.