Sequential changes in synaptic vesicle pools and endosome-like organelles during depolarization near the active zone of central nerve terminals

Neuroscience. 2002;109(1):195-206. doi: 10.1016/s0306-4522(01)00450-x.


During periods of high-frequency stimulation the maintenance of synaptic transmission depends on a continued supply of synaptic vesicles. Local recycling in the terminals ensures synaptic vesicle replenishment, but the intermediate steps are still a matter of debate. We analyzed changes in synaptic vesicle pools and endosome-like organelles near the active zone in central nerve terminals during depolarization at the ultrastructural level by electron microscopy. A short, 100 ms, depolarization-induced recruitment of synaptic vesicles was observed from a reserve pool to a recruited pool, within 150 nm of the active zone, and the docked pool at the active zone was increased as well. Prolonged, 15 s or 3 min, depolarization decreased the total amount of synaptic vesicles, which was accompanied by a parallel increase in size and amount of endosome-like organelles. After a period of rest, the number of endosome-like organelles decreased and the amount of synaptic vesicles was restored to control level. The endocytotic nature of part of the endosome-like organelles after 15 s and 3 min depolarization was indicated by their labeling with extracellularly added horseradish peroxidase (HRP). In addition, a small number of synaptic vesicles entrapped HRP under these conditions. After repolarization, the number of HRP-loaded endosome-like structures decreased. Simultaneously, a strong increase in amount of HRP-loaded small vesicles did occur. These results indicate that during sub-second depolarization, synaptic vesicles were rapidly recruited from the reserve pool to replenish the releasable pool, whereas prolonged depolarization (s-min) induced local endocytosis in at least two ways, i.e. either directly as vesicles or via endosome-like organelles from which synaptic vesicles were reformed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Central Nervous System / metabolism*
  • Central Nervous System / ultrastructure
  • Endosomes / drug effects
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • Horseradish Peroxidase
  • Mice
  • Mice, Inbred C57BL
  • Neurotransmitter Agents / metabolism
  • Potassium / pharmacology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Presynaptic Terminals / ultrastructure
  • Synaptic Membranes / drug effects
  • Synaptic Membranes / metabolism*
  • Synaptic Membranes / ultrastructure
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism*
  • Synaptic Vesicles / ultrastructure
  • Synaptosomes / metabolism
  • Synaptosomes / ultrastructure


  • Neurotransmitter Agents
  • Horseradish Peroxidase
  • Potassium