Metabotropic γ-aminobutyric acid type B (GABAB) 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 GABAB receptors. A GABAB antagonist and a G-protein uncoupler suppressed these effects. Low-concentration baclofen, a GABAB agonist, augmented mGluR1-mediated excitatory synaptic current produced by stimulating PFs. These results indicate that postsynaptic GABAB 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.
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We thank J. Bockaert, T. Murakoshi, D. Rusakov, F. Saitow and K. Yoshioka for comments on the manuscript and Novartis Pharma (Basel, Switzerland) for the gift of CGP62349. This work was supported in part by a Grant-in-Aid 0727910 (T.Y.) from the Ministry of Education, Science, Sports and Culture of Japan, and Grant-in-Aids 96L00310 (T.Y.) and 12780603 (M.H.) from the Japan Society for Promotion of Science. S.K. is a research director of CREST, JST (Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation).
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Hirono, M., Yoshioka, T. & Konishi, S. GABAB receptor activation enhances mGluR-mediated responses at cerebellar excitatory synapses. Nat Neurosci 4, 1207–1216 (2001). https://doi.org/10.1038/nn764
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