Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells

Tina Pangrsic (1) , Livia Lasarow (1) , Kirsten Reuter (1) , Hideki Takago (1) , Martin Schwander (1) , Dietmar Riedel (1) , Thomas Frank (1) , Lisa M Tarantino (1) , Janice Bailey (1) , Nicola Strenzke (1) , Nils Brose (1) , Ulrich Mueller (1) , Ellen Reisinger (1) , Tobias Moser (1)

1 InnerEarLab, Dept. of Otolaryngology

Inner hair cell (IHC) ribbon synapses indefatigably transmit acoustic information. The proteins mediating their fast vesicle replenishment (hundreds of vesicles/s) are unknown. Here we show that an Asp to Gly substitution in the CF domain of the synaptic vesicle protein otoferlin impairs hearing by reducing vesicle replenishment in the pachanga mouse model of human deafness DFNB9. estimates of vesicle docking, the readily releasable vesicle pool (RRP), Ca signaling and vesicle fusion were normal. Moreover, we observed postsynaptic excitatory currents of variable size and spike generation. However, mutant active zones (AZs) replenished vesicles at lower rates, and sound-evoked spiking in auditory neurons was sparse and only partially improved during longer inter-stimulus intervals. We conclude that replenishment does not keep up with release of vesicles at mutant AZs , such that a sufficient standing RRP cannot be maintained. We propose a novel role of otoferlin in replenishing synaptic vesicles.

Mots clés: Sensory Systems; Synaptic Transmission; Neurophysiology

Tina Pangrsic, Livia Lasarow, Kirsten Reuter, Hideki Takago, Martin Schwander, et al.. Hearing requires otoferlin-dependent efficient replenishment of synaptic vesicles in hair cells. Nature Neuroscience, 2010, ⟨10.1038/nn.2578⟩. ⟨hal-00548216⟩