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

Glitsch, Maike. Selective inhibition of spontaneous but not Ca dependent release machinery by presynaptic group II mGluRs in rat cerebellar slices. J Neurophysiol 96: 86–96, 2006. First published April 12, 2006; doi:10.1152/jn.01282.2005. Two main forms of neurotransmitter release are known: action potential-evoked and spontaneous release. Action potential-evoked release depends on Ca entry through voltage-gated Ca channels, whereas spontaneous release is thought to be Ca -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 interneuronPurkinje cell synapse activation of presynaptic group II metabotropic glutamate receptors suppresses spontaneous GABA release through a mechanism independent of voltage-gated Ca channels, store-operated Ca channels, and Ca release from intracellular Ca stores, suggesting that the metabotropic receptors target the release machinery directly. Voltage gated Ca channel-independent release following increased presynaptic cAMP production is similarly inhibited by these metabotropic receptors. In contrast, both voltage-gated Ca channel-dependent and presynaptic N-methyl-D-aspartate receptordependent GABA release were unaffected by activation of group II metabotropic glutamate receptors. Hence, the mechanisms underlying spontaneous and Ca -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.