Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse

Nature. 2003 Aug 14;424(6950):775-8. doi: 10.1038/nature01859.


Second messenger cascades involving G proteins and calcium are known to modulate neurotransmitter release. A prominent effect of such a cascade is the downmodulation of presynaptic calcium influx, which markedly reduces evoked neurotransmitter release. Here we show that G-protein-mediated signalling, such as through GABA (gamma-amino butyric acid) subtype B (GABA(B)) receptors, retards the recruitment of synaptic vesicles during sustained activity and after short-term depression. This retardation occurs through a lowering of cyclic AMP, which blocks the stimulatory effect of increased calcium concentration on vesicle recruitment. In this signalling pathway, cAMP (functioning through the cAMP-dependent guanine nucleotide exchange factor) and calcium/calmodulin cooperate to enhance vesicle priming. The differential modulation of the two forms of synaptic plasticity, presynaptic inhibition and calcium-dependent recovery from synaptic depression, is expected to have interesting consequences for the dynamic behaviour of neural networks.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Baclofen / pharmacology
  • Brain Stem / cytology
  • Brain Stem / drug effects
  • Brain Stem / metabolism
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calmodulin / metabolism
  • Cyclic AMP / metabolism
  • Cyclic AMP / pharmacology
  • Excitatory Postsynaptic Potentials / physiology
  • Guanosine Triphosphate / metabolism
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, GABA-B / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism*
  • Synaptic Transmission / drug effects
  • Synaptic Vesicles / drug effects
  • Synaptic Vesicles / metabolism*


  • Calmodulin
  • Receptors, GABA-B
  • Guanosine Triphosphate
  • Cyclic AMP
  • Heterotrimeric GTP-Binding Proteins
  • Baclofen
  • Calcium