Selective inhibition of spontaneous but not Ca2+ -dependent release machinery by presynaptic group II mGluRs in rat cerebellar slices.

Two main forms of neurotransmitter release are known: action potential-evoked and spontaneous release. Action potential-evoked release depends on Ca2+ entry through voltage-gated Ca2+ channels, whereas spontaneous release is thought to be Ca2+ -independent. Generally, spontaneous and action potential-evoked release are believed to use the same release machinery to release neurotransmitter. This study shows, using the whole cell patch-clamp technique in rat cerebellar slices, that at the interneuron- Purkinje cell synapse activation of presynaptic group II metabotropic glutamate receptors suppresses spontaneous GABA release through a mechanism independent of voltage-gated Ca2+ channels, store-operated Ca2+ channels, and Ca2+ release from intracellular Ca2+ stores, suggesting that the metabotropic receptors target the release machinery directly. Voltage gated Ca2+ channel-independent release following increased presynaptic cAMP production is similarly inhibited by these metabotropic receptors. In contrast, both voltage-gated Ca2+ channel-dependent and presynaptic N-methyl-D-aspartate receptor-dependent GABA release were unaffected by activation of group II metabotropic glutamate receptors. Hence, the mechanisms underlying spontaneous and Ca2+ -dependent GABA release are distinct in that only the former is blocked by group II metabotropic glutamate receptors. Thus the same neurotransmitter, glutamate, can activate or inhibit neurotransmitter release by selecting different receptors that target different release machineries.