Auditory Steady-State Responses (ASSR) und transiente auditorische Hirnstammpotenziale: Evaluation und Hörschwellenvergleich an Mausmodellen der sensorineuralen Schwerhörigkeit

Abstract

Auditory Steady-State Responses (ASSR) and transient auditory brainstem responses: evaluation and comparison of hearing thresholds based on mouse models of sensorineural hearing loss. The present study compares two objective hearing tests in normal hearing and hearing impaired mice to differentiate the underlying pathomechanisms of sensorineural hearing loss (SNHL). SNHL is caused by diverse pathologies of the inner ear or the auditory nerve. Up to date a clear correlation between the different phenotypes of hearing loss and specific defects has not been established. Based on two defined mouse models of SNHL (Bassoon and KCNQ4) we evaluated the practicability of Auditory Steady-State Responses (ASSR). Initially ASSR recordings were for the first time established and described in normal hearing animals. Within three ranges of modulation frequencies (below 200 Hz, between 200-600 Hz and beyond 600 Hz) ASSR in mice could be generated with steady results. ASSR thresholds were compared to the thresholds of the Auditory Brainstem Response (ABR). The subjective-visually and objective-statistically acquired ASSR thresholds did both not differ from the corresponding ABR thresholds. In the following part of the study ASSR- and ABR recordings were recorded in the SNHL mouse model. Animals bearing defects of the outer hair cells amplifier system (KCNQ4 KO) and animals with a defect of the inner hair cell synaptic transmission (Bassoon mutant) were investigated. The ASSR thresholds were comparable to the ABR thresholds in both groups. Both mutants showed an increase of ASSR- and ABR threshold of approximately 40 dB SPL compared to normal hearing animals of the same age. Animals with a defect of the amplifier system displayed a steep rise of the ASSR- and ABR amplitudes (with increasing sound intensity) near the auditory threshold. This recruitment phenomenon reflects probably a strong activation of synchronized neuronal activity beyond the auditory threshold. In contrast the amplitudes of the ASSR and ABR responses of mice with impaired synaptic transmission augmented very little with increasing sound intensity, which reflects the disturbed signal transmission at the ribbon deficient synapses. In summary ASSR, as an established electrophysiological method, allow a rapid, frequency-specific and objective assessment of the hearing threshold in mice. Together with the ABR and otoacustic emissions it was possible to create an audiological profile of SNHL, which can contribute to the differential diagnosis of SNHL.