Dynamic assembly of ribbon synapses and circuit maintenance in a vertebrate sensory system

Nat Commun. 2019 May 15;10(1):2167. doi: 10.1038/s41467-019-10123-1.

Abstract

Ribbon synapses transmit information in sensory systems, but their development is not well understood. To test the hypothesis that ribbon assembly stabilizes nascent synapses, we performed simultaneous time-lapse imaging of fluorescently-tagged ribbons in retinal cone bipolar cells (BCs) and postsynaptic densities (PSD95-FP) of retinal ganglion cells (RGCs). Ribbons and PSD95-FP clusters were more stable when these components colocalized at synapses. However, synapse density on ON-alpha RGCs was unchanged in mice lacking ribbons (ribeye knockout). Wildtype BCs make both ribbon-containing and ribbon-free synapses with these GCs even at maturity. Ribbon assembly and cone BC-RGC synapse maintenance are thus regulated independently. Despite the absence of synaptic ribbons, RGCs continued to respond robustly to light stimuli, although quantitative examination of the responses revealed reduced frequency and contrast sensitivity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured
  • Disks Large Homolog 4 Protein / genetics
  • Disks Large Homolog 4 Protein / metabolism
  • Intravital Microscopy / methods
  • Light
  • Luminescent Proteins / chemistry
  • Luminescent Proteins / genetics
  • Mice
  • Mice, Transgenic
  • Microscopy, Fluorescence / methods
  • Photic Stimulation
  • Primary Cell Culture
  • Red Fluorescent Protein
  • Retinal Bipolar Cells / physiology
  • Retinal Cone Photoreceptor Cells / physiology*
  • Retinal Ganglion Cells / physiology
  • Synapses / metabolism*
  • Synaptic Transmission / physiology*
  • Time-Lapse Imaging / methods

Substances

  • Disks Large Homolog 4 Protein
  • Dlg4 protein, mouse
  • Luminescent Proteins