Disruption of the presynaptic cytomatrix protein bassoon degrades ribbon anchorage, multiquantal release, and sound encoding at the hair cell afferent synapse

Zhizi Jing, Mark A. Rutherford, Hideki Takago, Thomas Frank, Anna Fejtova, Darina Khimich, Tobias Moser, Nicola Strenzke

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Inner hair cells (IHCs) of the cochlea use ribbon synapses to transmit auditory information faithfully to spiral ganglion neurons (SGNs). In the present study, we used genetic disruption of the presynaptic scaffold protein bassoon in mice to manipulate the morphology and function of the IHC synapse. Although partial-deletion mutants lacking functional bassoon (BsnΔEx4/5) had a near-complete loss of ribbons from the synapses (up to 88% ribbonless synapses), gene-trap mutants (Bsngt) showed weak residual expression of bassoon and 56% ribbonless synapses, whereas the remaining 44% had a loosely anchored ribbon. Patch-clamp recordings and synaptic CaV1.3 immunolabeling indicated a larger number of Ca2+ channels for Bsngt IHCs compared with BsnΔEx4/5 IHCs and for Bsngt ribbonoccupied versus Bsngt ribbonless synapses. An intermediate phenotype of Bsngt IHCs was also found by membrane capacitance measurements for sustained exocytosis, but not for the size of the readily releasable vesicle pool. The frequency and amplitude of EPSCs were reduced in BsnΔEx4/5 mouse SGNs, whereas their postsynaptic AMPA receptor clusters were largely unaltered. Sound coding in SGN, assessed by recordings of single auditory nerve fibers and their population responses in vivo, was similarly affected in Bsngt and BsnΔEx4/5 mice. Both genotypes showed impaired sound onset coding and reduced evoked and spontaneous spike rates. In summary, reduced bassoon expression or complete lack of full-length bassoon impaired sound encoding to a similar extent, which is consistent with the comparable reduction of the readily releasable vesicle pool. This suggests that the remaining loosely anchored ribbons in gt IHCs were functionally inadequate or that ribbon independent mechanisms dominated the coding deficit.

Original languageEnglish
Pages (from-to)4456-4467
Number of pages12
JournalJournal of Neuroscience
Volume33
Issue number10
DOIs
StatePublished - Mar 6 2013

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