Role of the ribbon synapse in high-frequency neural phase locking

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In humans and animals with good low-frequency hearing, phase locking by the afferent fibres of the auditory nerve is known to be a salient temporal code for the central auditory system. The temporal dispersion of spiking in phase-locking auditory-nerve fibres can be as low as 30 µs. This represents ultrafast and temporally precise information processing at its extreme. However, the underlying cellular mechanisms are not well understood. This project aims to explore the specific role of the hair-cell ribbon synapse in this process. The chicken is chosen as the model organism because it combines 1) robust auditory-nerve phase-locking into the kHz-range with 2) good accessibility of early embryonic stages in-ovo for established techniques of virus-mediated gene misexpression. We have a chicken model available with an aberrant phenotype in one ear that specifically changes the hair cells and their innervation, such that an increased number of synaptic ribbons connects to each afferent fibre. This will allow for testing the recently suggested mechanism that tightly synchronised multi-vesicular transmitter release is crucial for the normal temporal precision observed in neural phase locking. We predict that, especially near the upper frequency limit of phase locking, an increased number of ribbon sites will degrade the synchronisation and thus degrade the temporal precision of spiking. This will be quantified with several metrics in vivo. Our bird work will complement ongoing work on mouse hair cells by extending the concepts and available toolbox for unravelling the mechanisms for ultrafast processing at this very specialised first synapse in the auditory pathway.