Regulation of synaptic transmission is a widespread means for dynamic alter
ations in nervous system function. In several cases, this regulation target
s vesicular recycling in presynaptic terminals and may result in substantia
l changes in efficiency of synaptic transmission. Traditionally, experiment
al accessibility of the synaptic vesicle cycle in central neuronal synapses
has been largely limited to the exocytotic side, which can be monitored wi
th electrophysiological responses to neurotransmitter release. Recently, ph
ysiological measurements on the endocytotic portion of the cycle have been
made possible by the introduction of styryl dyes such as FM1-43 as fluoresc
ent markers for recycling synaptic vesicles. Here we demonstrate the existe
nce of fast endocytosis in hippocampal nerve terminals and derive its kinet
ics from fluorescence measurements using dyes with varying rates of membran
e departitioning. The rapid mode of vesicular retrieval was greatly speeded
by exposure to staurosporine or elevated extracellular calcium. The effect
ive time-constant for retrieval can be <2 seconds under appropriate conditi
ons. Thus, hippocampal synapses capitalize on efficient mechanisms for endo
cytosis and their vesicular retrieval is subject to modulatory control.