Role of presynaptic metabotropic glutamate receptors in the induction of long-term synaptic plasticity of vesicular release

► Presynaptic mGluRs are key to short and long-term plasticity of transmitter release. ► mGluRs transiently inhibit vesicular release via release of Gβγ. ► Gβγ binding the SNAP-25 C-terminus is necessary, not sufficient, for LTD of release. ► Gαi2, Nitric oxide, cyclic GMP, cyclic ADP ribose, CaMKinase are all necessary for LTD.