Mechanisms, pools, and sites of spontaneous vesicle release at synapses of rod and cone photoreceptors

Eur J Neurosci. 2016 Aug;44(3):2015-27. doi: 10.1111/ejn.13288. Epub 2016 Jun 22.


Photoreceptors have depolarized resting potentials that stimulate calcium-dependent release continuously from a large vesicle pool but neurons can also release vesicles without stimulation. We characterized the Ca(2+) dependence, vesicle pools, and release sites involved in spontaneous release at photoreceptor ribbon synapses. In whole-cell recordings from light-adapted horizontal cells (HCs) of tiger salamander retina, we detected miniature excitatory post-synaptic currents (mEPSCs) when no stimulation was applied to promote exocytosis. Blocking Ca(2+) influx by lowering extracellular Ca(2+) , by application of Cd(2+) and other agents reduced the frequency of mEPSCs but did not eliminate them, indicating that mEPSCs can occur independently of Ca(2+) . We also measured release presynaptically from rods and cones by examining quantal glutamate transporter anion currents. Presynaptic quantal event frequency was reduced by Cd(2+) or by increased intracellular Ca(2+) buffering in rods, but not in cones, that were voltage clamped at -70 mV. By inhibiting the vesicle cycle with bafilomycin, we found the frequency of mEPSCs declined more rapidly than the amplitude of evoked excitatory post-synaptic currents (EPSCs) suggesting a possible separation between vesicle pools in evoked and spontaneous exocytosis. We mapped sites of Ca(2+) -independent release using total internal reflectance fluorescence (TIRF) microscopy to visualize fusion of individual vesicles loaded with dextran-conjugated pHrodo. Spontaneous release in rods occurred more frequently at non-ribbon sites than evoked release events. The function of Ca(2+) -independent spontaneous release at continuously active photoreceptor synapses remains unclear, but the low frequency of spontaneous quanta limits their impact on noise.

Keywords: calcium; exocytosis; retina; ribbon synapse; spontaneous synaptic release; tiger salamander.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Excitatory Postsynaptic Potentials*
  • Exocytosis*
  • Female
  • Glutamic Acid / metabolism
  • Male
  • Retinal Cone Photoreceptor Cells / metabolism*
  • Retinal Cone Photoreceptor Cells / physiology
  • Retinal Rod Photoreceptor Cells / metabolism*
  • Retinal Rod Photoreceptor Cells / physiology
  • Synaptic Vesicles / metabolism*
  • Urodela


  • Glutamic Acid
  • Calcium