High-frequency firing helps replenish the readily releasable pool of synaptic vesicles

Nature. 1998 Jul 23;394(6691):384-8. doi: 10.1038/28645.


Synapses in the central nervous system undergo various short- and long-term changes in their strength, but it is often difficult to distinguish whether presynaptic or postsynaptic mechanisms are responsible for these changes. Using patch-clamp recording from giant synapses in the mouse auditory brainstem, we show here that short-term synaptic depression can be largely attributed to rapid depletion of a readily releasable pool of vesicles. Replenishment of this pool is highly dependent on the recent history of synaptic activity. High-frequency stimulation of presynaptic terminals significantly enhances the rate of replenishment. Broadening the presynaptic action potential with the potassium-channel blocker tetraethylammonium, which increases Ca2+ entry, further enhances the rate of replenishment. As this increase can be suppressed by the Ca2+-channel blocker Cd2+ or by the Ca2+ buffer EGTA, we conclude that Ca2+ influx through voltage-gated Ca2+ channels is the key signal that dynamically regulates the refilling of the releasable pool of synaptic vesicles in response to different patterns of inputs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials
  • Animals
  • Auditory Pathways / physiology
  • Calcium / physiology
  • Egtazic Acid / analogs & derivatives
  • Egtazic Acid / pharmacology
  • Excitatory Postsynaptic Potentials
  • In Vitro Techniques
  • Kinetics
  • Mice
  • Patch-Clamp Techniques
  • Pons / physiology
  • Potassium Channel Blockers
  • Receptors, AMPA / physiology
  • Synaptic Transmission / physiology*
  • Synaptic Vesicles / physiology*
  • Tetraethylammonium / pharmacology


  • Potassium Channel Blockers
  • Receptors, AMPA
  • Egtazic Acid
  • Tetraethylammonium
  • EGTA acetoxymethyl ester
  • Calcium