Vesicle sub-pool organization at inner hair cell ribbon synapses

EMBO Rep. 2018 Nov;19(11):e44937. doi: 10.15252/embr.201744937. Epub 2018 Sep 10.


The afferent inner hair cell synapse harbors the synaptic ribbon, which ensures a constant vesicle supply. Synaptic vesicles (SVs) are arranged in morphologically discernable pools, linked via filaments to the ribbon or the presynaptic membrane. We propose that filaments play a major role in SV resupply and exocytosis at the ribbon. Using advanced electron microscopy, we demonstrate that SVs are organized in sub-pools defined by the filament number per vesicle and its connections. Upon stimulation, SVs increasingly linked to other vesicles and to the ribbon, whereas single-tethered SVs dominated at the membrane. Mutant mice for the hair cell protein otoferlin (pachanga, OtofPga/Pga ) are profoundly deaf with reduced sustained release, serving as a model to investigate the SV replenishment at IHCs. Upon stimulation, multiple-tethered and docked vesicles (rarely observed in wild-type) accumulated at OtofPga/Pga active zones due to an impairment downstream of docking. Conclusively, vesicles are organized in sub-pools at ribbon-type active zones by filaments to support vesicle supply, transport, and finally release.

Keywords: exocytosis; high‐pressure freezing; ribbon synapse; sub‐pools; synaptic vesicle tethering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism
  • Deafness / genetics
  • Exocytosis
  • Hair Cells, Auditory, Inner / cytology*
  • Hair Cells, Auditory, Inner / pathology
  • Membrane Proteins / genetics
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Microscopy, Electron, Transmission
  • Mutation
  • Synapses / physiology
  • Synapses / ultrastructure*
  • Synaptic Vesicles / physiology*
  • Synaptic Vesicles / ultrastructure


  • Membrane Proteins
  • otoferlin protein, mouse