GABAB receptor activation enhances mGIuR-mediated responses at cerebellar excitatory synapses

Metabotropic gamma -aminobutyric acid type B (GABA(B)) and glutamate receptors (mGluRs) are postsynaptically co-expressed at cerebellar parallel fiber (PF)-Purkinje cell (PC) excitatory synapses, but their functional interactions are unclear. We found that mGluR1 agonist-induced currents and [Ca2+](i) increases in PCs were enhanced following co-activation of GABA(B) receptors. A GABA(B) antagonist and a G-protein uncoupler suppressed these effects. Low-concentration baclofen, a GABA(B) agonist, augmented mGluR1-mediated excitatory synaptic current produced by stimulating PFs. These results indicate that postsynaptic GABA(B) receptors functionally interact with mGluR1 and enhance mGluR1-mediated excitatory transmission at PF-PC synapses. The interaction between the two types of metabotropic receptors provides a likely mechanism for regulating cerebellar synaptic plasticity.