Molecular physiology of the inner hair cell ribbon synapses

Abstract

During this work we investigated organization, molecular composition and function of hair cell ribbon synapses. We demonstrated RIBEYE, Bassoon and Piccolo to be components of IHC synaptic ribbons. In the present study we showed that anchoring of IHC ribbons is impaired in mouse mutants for the presynaptic scaffolding protein Bassoon. The lack of active, zone-anchored synaptic ribbons reduced the presynaptic readily releasable vesicle pool, and impaired synchronous auditory signalling as revealed by recordings of exocytic IHC capacitance changes and sound-evoked activation of spiral ganglion neurons. Both exocytosis of the hair cell releasable vesicle pool and the number of synchronously activated spiral ganglion neurons co-varied with the number of anchored ribbons during development. Interestingly, ribbon-deficient IHCs were still capable of sustained exocytosis with normal Ca2+-dependence. Endocytic membrane retrieval was intact, but an accumulation of tubular and cisternal membrane profiles was observed in ribbon-deficient IHCs. We conclude that ribbon-dependent synchronous release of multiple vesicles at the hair cell afferent synapse is essential for normal hearing. In addition, our study presents a molecularly defined mouse model for human auditory neuropathy and characterizes it as a synaptic audiopathy.