Sound encoding in the inferior colliculus of otoferlin Ile515Thr mutant mice

Otoferlin is an inner hair cell specific protein, which is essential for neurotransmitter release and hearing. In human patients, the OTOF Ile515Thr point mutation causes only a mild increase in hearing thresholds, but a severe speech perception deficit, impaired adaptation to continuous sounds and auditory fatigue. Mice with the same mutation have less Otoferlin in the cell membrane of inner hair cells, reduced exocytosis and abnormal auditory brainstem responses.

We now analyze how this peripheral deficit affects sound encoding in higher centers of the auditory pathway, particularly the inferior colliculus. Therefore, we compare data from in vivo single unit recordings from spiral ganglion neurons of Otof(I515T/I515) mice with those of neurons from the inferior colliculus.

Single neurons from mutant mice show normal spontaneous spiking, frequency tuning and thresholds, but reduced spike rates with a striking dependence on repetition rate and stimulus duration. Furthermore, the phase locking to amplitude modulated tones is impaired and the depression of spiking in response to a probe tone after a short silent interval between paired tones was more pronounced.

Single unit recordings from mutant mice indicate an unusual sound encoding deficit with a use-dependent reduction of spikerates. We believe that this reflects impaired vesicle reformation at the inner hair cell ribbon synapse due to reduced levels of functional otoferlin. The peripheral deficit in the encoding of amplitude modulated and paired tones cannot be fully compensated up to the level of the inferior colliculus, although the defect seems not to be as severe as in the auditory nerve. The resulting gap detection deficit likely contributes to the communication problems of human patients with otoferlin mutations.

Publication History

Publication Date:
18 April 2018 (online)