Direct modulation of synaptic vesicle priming by GABAB receptor activation at a glutamatergic synapse

Nature volume 424, pages775–778(2003)Cite this article

Abstract

Second messenger cascades involving G proteins1,2 and calcium3 are known to modulate neurotransmitter release4,5. A prominent effect of such a cascade is the downmodulation of presynaptic calcium influx6,7, which markedly reduces evoked neurotransmitter release5,7,8. Here we show that G-protein-mediated signalling, such as through GABA (γ-amino butyric acid) subtype B (GABAB) 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.

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Figure 1: Effects of baclofen on synaptic transmission at the calyx of Held.
Figure 2: Inhibitory effect of baclofen on vesicle recruitment.
Figure 3: Supplementation of cAMP prevents the inhibitory effect of GDP-βS.

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Acknowledgements

We thank N. Brose, F. Felmy, C. Rosenmund, F. Sachs, R. Schneggenburger, G. Schultz and M. Wölfel for critical comments on the manuscript. This work was supported in part by a grant from the Deutsche Forschungsgemeinschaft (DFG Research Center on Molecular Physiology of the Brain).

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  1. Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, 37077, Göttingen, Germany

    Takeshi Sakaba & Erwin Neher

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  1. Takeshi Sakaba
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  2. Erwin Neher
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Correspondence to Erwin Neher.

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Sakaba, T., Neher, E. Direct modulation of synaptic vesicle priming by GABAB receptor activation at a glutamatergic synapse. Nature 424, 775–778 (2003). https://doi.org/10.1038/nature01859

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