Piccolino is required for ribbon architecture at cochlear inner hair cell synapses and for hearing

Abstract

Abstract Cochlear inner hair cells (IHCs) form specialized ribbon synapses with spiral ganglion neurons that tirelessly transmit sound information at high rates over long time periods with extreme temporal precision. This functional specialization is essential for sound encoding and is attributed to a distinct molecular machinery with unique players or splice variants compared to conventional neuronal synapses. Among these is the active zone (AZ) scaffold protein piccolo/aczonin, which is represented by its short splice variant piccolino at cochlear and retinal ribbon synapses. While the function of piccolo at synapses of the central nervous system has been intensively investigated, the role of piccolino at IHC synapses remains unclear. In this study, we characterize the structure and function of IHC synapses in piccolo gene‐trap mutant rats ( Pclo gt/gt ). We find a mild hearing deficit with elevated thresholds and reduced amplitudes of auditory brainstem responses. Ca 2+ channel distribution and ribbon morphology are altered in apical IHCs, while their presynaptic function seems to be unchanged. We conclude that piccolino contributes to the AZ organization in IHCs and is essential for normal hearing.

Synopsis image Piccolino regulates ribbon morphology as well as the arrangement of Ca 2+ channels at cochlear ribbon synapses. Lack of piccolino results in mild hearing impairment. Rats lacking piccolino show elevated thresholds and reduced amplitudes of auditory brainstem responses for middle and high sound frequencies, indicating an impairment in synchronous synaptic transmission of sound information. Disruption of piccolino results in two distinct categories of active zones with different ribbon synapse morphologies in mutant inner hair cells, while tethering of synaptic vesicles is normal. Ca 2+ channel clustering is impaired in piccolino‐deficient hair cells, but Ca 2+ currents and exocytosis are unaffected.