High-frequency firing helps replenish the readily releasable pool of synaptic vesicles.
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.
Division of Neurology & The Program in Brain and Behavior, The Hospital for Sick Children, Department of Physiology, University of Toronto, Ontario, Canada.
L Y
LY
Wang
L K
LK
Kaczmarek
D000200:Action Potentials; D000818:Animals; D001306:Auditory Pathways / Q000502:physiology; D002118:Calcium / Q000502:physiology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D007700:Kinetics; D051379:Mice; D018408:Patch-Clamp Techniques; D011149:Pons / Q000502:physiology; D026902:Potassium Channel Blockers; D018091:Receptors, AMPA / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*; D019789:Tetraethylammonium / Q000494:pharmacology
D026902:Potassium Channel Blockers; D018091:Receptors, AMPA; D004533:Egtazic Acid; D019789:Tetraethylammonium; C046770:EGTA acetoxymethyl ester; D002118:Calcium