These authors have contributed equally to the work.
Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson’s disease treatment
Article first published online: 14 MAR 2009
Journal Compilation © 2009 International Society for Neurochemistry. No claim to original US government works
Journal of Neurochemistry
Volume 109, Issue 4, pages 1096–1105, May 2009
How to Cite
Cuomo, D., Martella, G., Barabino, E., Platania, P., Vita, D., Madeo, G., Selvam, C., Goudet, C., Oueslati, N., Pin, J.-P., Acher, F., Pisani, A., Beurrier, C., Melon, C., Kerkerian-Le Goff, L. and Gubellini, P. (2009), Metabotropic glutamate receptor subtype 4 selectively modulates both glutamate and GABA transmission in the striatum: implications for Parkinson’s disease treatment. Journal of Neurochemistry, 109: 1096–1105. doi: 10.1111/j.1471-4159.2009.06036.x
- Issue published online: 14 APR 2009
- Article first published online: 14 MAR 2009
- Received November 7, 2008; revised manuscript received March 3, 2009; accepted March 4, 2009.
- γ-aminobutyric acid;
- basal ganglia;
- metabotropic glutamate receptor
Alterations of striatal synaptic transmission have been associated with several motor disorders involving the basal ganglia, such as Parkinson’s disease. For this reason, we investigated the role of group-III metabotropic glutamate (mGlu) receptors in regulating synaptic transmission in the striatum by electrophysiological recordings and by using our novel orthosteric agonist (3S)-3-[(3-amino-3-carboxypropyl(hydroxy)phosphinyl)-hydroxymethyl]-5-nitrothiophene (LSP1-3081) and l-2-amino-4-phosphonobutanoate (L-AP4). Here, we show that both drugs dose-dependently reduced glutamate- and GABA-mediated post-synaptic potentials, and increased the paired-pulse ratio. Moreover, they decreased the frequency, but not the amplitude, of glutamate and GABA spontaneous and miniature post-synaptic currents. Their inhibitory effect was abolished by (RS)-α-cyclopropyl-4-phosphonophenylglycine and was lost in slices from mGlu4 knock-out mice. Furthermore, (S)-3,4-dicarboxyphenylglycine did not affect glutamate and GABA transmission. Finally, intrastriatal LSP1-3081 or L-AP4 injection improved akinesia measured by the cylinder test. These results demonstrate that mGlu4 receptor selectively modulates striatal glutamate and GABA synaptic transmission, suggesting that it could represent an interesting target for selective pharmacological intervention in movement disorders involving basal ganglia circuitry.