Recruitment of resting vesicles into recycling pools supports NMDA receptor-dependent synaptic potentiation in cultured hippocampal neurons

J Physiol. 2012 Apr 1;590(7):1585-97. doi: 10.1113/jphysiol.2011.226688. Epub 2012 Jan 23.


Most presynaptic terminals in the central nervous system are characterized by two functionally distinct vesicle populations: a recycling pool, which supports action potential-driven neurotransmitter release via vesicle exocytosis, and a resting pool. The relative proportions of these two pools are highly variable between individual synapses, prompting speculation on their specific relationship, and on the possible functions of the resting pool.Using fluorescence imaging of FM-styryl dyes and synaptophysinI-pHluorin(sypHy) as well as correlative electronmicroscopy approaches, we show here that Hebbian plasticity-dependent changes in synaptic strength in rat hippocampal neurons can increase the recycling pool fraction at the expense of the resting pool in individual synaptic terminals. This recruitment process depends on NMDA-receptor activation, nitric oxide signalling and calcineurin and is accompanied by an increase in the probability of neurotransmitter release at individual terminals. Blockade of actin-mediated intersynaptic vesicle exchange does not prevent recycling pool expansion demonstrating that vesicle recruitment is intrasynaptic.We propose that the conversion of resting pool vesicles to the functionally recycling pool provides a rapid mechanism to implement long-lasting changes in presynaptic efficacy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcineurin / physiology
  • Calcineurin Inhibitors
  • Enzyme Inhibitors / pharmacology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Neurons / physiology*
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Nitric Oxide Synthase / physiology
  • Nitroarginine / pharmacology
  • Presynaptic Terminals / physiology*
  • Rats
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Synaptic Transmission / physiology
  • Synaptic Vesicles / physiology*
  • Tacrolimus / pharmacology


  • Calcineurin Inhibitors
  • Enzyme Inhibitors
  • Receptors, N-Methyl-D-Aspartate
  • Nitroarginine
  • Nitric Oxide Synthase
  • Calcineurin
  • Tacrolimus