Onset Coding Is Degraded in Auditory Nerve Fibers from Mutant Mice Lacking Synaptic Ribbons

Synaptic ribbons, found at the presynaptic membrane of sensory cells in both ear and eye, have been implicated in the vesicle-pool dynamics of synaptic transmission. To elucidate ribbon function, we characterized the response properties of single auditory nerve fibers in mice lacking Bassoon, a scaffolding protein involved in anchoring ribbons to the membrane. In bassoon mutants, immunohistochemistry showed that fewer than 3% of the hair cells' afferent synapses retained anchored ribbons. Auditory nerve fibers from mutants had normal threshold, dynamic range, and postonset adaptation in response to tone bursts, and they were able to phase lock with normal precision to amplitude-modulated tones. However, spontaneous and sound-evoked discharge rates were reduced, and the reliability of spikes, particularly at stimulus onset, was significantly degraded as shown by an increased variance of first-spike latencies. Modeling based on in vitro studies of normal and mutant hair cells links these findings to reduced release rates at the synapse. The degradation of response reliability in these mutants suggests that the ribbon and/or Bassoon normally facilitate high rates of exocytosis and that its absence significantly compromises the temporal resolving power of the auditory system.National Institute on Deafness and Other Communication Disorders (U.S.) (Grant RO1 DC00188)National Institute on Deafness and Other Communication Disorders (U.S.) (Grant P30 DC05209)Jack Kent Cooke graduate fellowshipDeutsche ForschungsgemeinschaftDeutsche Forschungsgemeinschaft (Center for Molecular Physiology of the Brain)Germany. Bundesministerium für Bildung und ForschungBernstein Center for Computational Neuroscience GöttingenEuropean Commission (Eurohear)Deutsche Forschungsgemeinschaft (SFB 779/B9