Complexin 3 Increases the Fidelity of Signaling in a Retinal Circuit by Regulating Exocytosis at Ribbon Synapses

Cell Rep. 2016 Jun 7;15(10):2239-2250. doi: 10.1016/j.celrep.2016.05.012. Epub 2016 May 26.


Complexin (Cplx) proteins modulate the core SNARE complex to regulate exocytosis. To understand the contributions of Cplx to signaling in a well-characterized neural circuit, we investigated how Cplx3, a retina-specific paralog, shapes transmission at rod bipolar (RB)→AII amacrine cell synapses in the mouse retina. Knockout of Cplx3 strongly attenuated fast, phasic Ca(2+)-dependent transmission, dependent on local [Ca(2+)] nanodomains, but enhanced slower Ca(2+)-dependent transmission, dependent on global intraterminal [Ca(2+)] ([Ca(2+)]I). Surprisingly, coordinated multivesicular release persisted at Cplx3(-/-) synapses, although its onset was slowed. Light-dependent signaling at Cplx3(-/-) RB→AII synapses was sluggish, owing largely to increased asynchronous release at light offset. Consequently, propagation of RB output to retinal ganglion cells was suppressed dramatically. Our study links Cplx3 expression with synapse and circuit function in a specific retinal pathway and reveals a role for asynchronous release in circuit gain control.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Calcium / pharmacology
  • Exocytosis* / drug effects
  • Eye Proteins / metabolism*
  • Mice, Inbred C57BL
  • Multivesicular Bodies / drug effects
  • Multivesicular Bodies / metabolism
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / metabolism*
  • Retina / cytology*
  • Retina / drug effects
  • Retina / metabolism*
  • Retinal Bipolar Cells / drug effects
  • Retinal Bipolar Cells / metabolism
  • Signal Transduction* / drug effects
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects


  • Adaptor Proteins, Signal Transducing
  • Cplx3 protein, mouse
  • Eye Proteins
  • Nerve Tissue Proteins
  • Calcium