Activity-dependent acceleration of endocytosis at a central synapse.
Accumulated evidence indicates the existence of rapid and slow endocytosis at many synapses. It has been proposed that rapid endocytosis is activated by intense stimulation when vesicle recycling needs to be speeded up to supply vesicles at hippocampal synapses. However, the evidence, as obtained with imaging techniques, which are somewhat indirect in indicating rapid endocytosis, is controversial. Furthermore, a slower time course of endocytosis is often found after more intense nerve activity, casting doubt on the role of rapid endocytosis at synapses. Here, we addressed this issue at a mammalian central synapse, the calyx of Held, using a capacitance measurement technique that provides a higher time resolution than imaging techniques. We found that rapid endocytosis with a time constant of approximately 1-2 s was activated during intense nerve activity. Reducing the presynaptic calcium current or buffering the intracellular calcium with EGTA significantly inhibited rapid endocytosis, suggesting that calcium triggers rapid endocytosis. During intense stimulation, rapid endocytosis retrieved up to approximately eight vesicles per second per active zone, approximately eightfold larger than reported in the hippocampus, and thus played a dominant role during and within 3 s after intense stimulation. Slow endocytosis became dominant 3 s after intense stimulation likely because of the fall of the intracellular calcium level that deactivated rapid endocytosis. These results underscore the importance of calcium-triggered rapid endocytosis, which offers the nerve terminal the plasticity to speed up vesicle cycling during intense nerve activity.
Wu
Wei
W
National Institute of Neurological Disorders and Stroke, Bethesda, Maryland 20892, USA.
Xu
Jianhua
J
Wu
Xin-Sheng
XS
Wu
Ling-Gang
LG
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D013997:Time Factors
D002118:Calcium