Direct modulation of synaptic vesicle priming by GABA(B) receptor activation at a glutamatergic synapse.
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.
Sakaba
Takeshi
T
Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, Göttingen 37077, Germany.
Neher
Erwin
E
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001933:Brain Stem / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D002147:Calmodulin / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism*
D002147:Calmodulin; D018080:Receptors, GABA-B; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D020962:Heterotrimeric GTP-Binding Proteins; D001418:Baclofen; D002118:Calcium