Induction of cerebellar long-term depression requires activation of glutamate metabotropic receptors.

In rat cerebellar slices, 500 microM (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) reversibly inhibited both dendritic and somatic increases in FLUO-3 fluorescence intensity induced by bath applications of 50-100 microM (+-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD). No effect of MCPG was observed on dendritically recorded excitatory postsynaptic potentials evoked by synaptic activation of either parallel or climbing fibres. Long-term depression of parallel fibre-Purkinje cell transmission, induced either by conjunctive activation of parallel and climbing fibres or by pairing parallel fibre stimulation with intradendritic injections of 8-BrcGMP, was not only prevented in the presence of MCPG but a robust long-term potentiation of responses consistently occurred. These data show that metabotropic glutamate receptor activation is necessary for the induction of LTD.