The synaptic ribbon is critical for sound encoding at high rates and with temporal precision

Elife. 2018 Jan 12:7:e29275. doi: 10.7554/eLife.29275.

Abstract

We studied the role of the synaptic ribbon for sound encoding at the synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in mice lacking RIBEYE (RBEKO/KO). Electron and immunofluorescence microscopy revealed a lack of synaptic ribbons and an assembly of several small active zones (AZs) at each synaptic contact. Spontaneous and sound-evoked firing rates of SGNs and their compound action potential were reduced, indicating impaired transmission at ribbonless IHC-SGN synapses. The temporal precision of sound encoding was impaired and the recovery of SGN-firing from adaptation indicated slowed synaptic vesicle (SV) replenishment. Activation of Ca2+-channels was shifted to more depolarized potentials and exocytosis was reduced for weak depolarizations. Presynaptic Ca2+-signals showed a broader spread, compatible with the altered Ca2+-channel clustering observed by super-resolution immunofluorescence microscopy. We postulate that RIBEYE disruption is partially compensated by multi-AZ organization. The remaining synaptic deficit indicates ribbon function in SV-replenishment and Ca2+-channel regulation.

Keywords: Ca2+-channels; active zone; cell biology; exocytosis; hearing; mouse; neuroscience; ribbon synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation
  • Alcohol Oxidoreductases
  • Animals
  • Co-Repressor Proteins
  • DNA-Binding Proteins / deficiency*
  • Hair Cells, Auditory, Inner / physiology*
  • Hearing*
  • Mice
  • Mice, Knockout
  • Microscopy, Electron
  • Microscopy, Fluorescence
  • Phosphoproteins / deficiency*
  • Spiral Ganglion / cytology*
  • Synapses / physiology*
  • Synapses / ultrastructure

Substances

  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Phosphoproteins
  • Alcohol Oxidoreductases
  • Ctbp2 protein, mouse