RT Journal Article
SR Electronic
T1 Metabotropic Glutamate 2 Receptors Modulate Synaptic Inputs and Calcium Signals in Striatal Cholinergic Interneurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6176
OP 6185
DO 10.1523/JNEUROSCI.22-14-06176.2002
VO 22
IS 14
A1 Pisani, Antonio
A1 Bonsi, Paola
A1 Catania, Maria Vincenza
A1 Giuffrida, Raffaella
A1 Morari, Michele
A1 Marti, Matteo
A1 Centonze, Diego
A1 Bernardi, Giorgio
A1 Kingston, Ann E.
A1 Calabresi, Paolo
YR 2002
UL http://www.jneurosci.org/content/22/14/6176.abstract
AB Striatal cholinergic interneurons were recorded from a rat slice preparation. Synaptic potentials evoked by intrastriatal stimulation revealed three distinct components: a glutamatergic EPSP, a GABAA-mediated depolarizing potential, and an acetylcholine (ACh)-mediated IPSP. The responses to group II metabotropic glutamate (mGlu) receptor activation were investigated on the isolated components of the synaptic potentials. Each pharmacologically isolated component was reversibly reduced by bath-applied LY379268 and ((2S,1′R,2′R,3′R)-2-(2,3-dicarboxylcyclopropyl)-glycine, group II agonists. In an attempt to define the relevance of group II mGlu receptor activation on cholinergic transmission, we focused on the inhibitory effect on the IPSP, which was mimicked and occluded by ω-agatoxin IVA (ω-Aga-IVA), suggesting a modulation on P-type high-voltage-activated calcium channels. Spontaneous calcium-dependent plateau-potentials (PPs) were recorded with cesium-filled electrodes plus tetraethylammonium and TTX in the perfusing solution, and measurements of intracellular calcium [Ca2+]i changes were obtained simultaneously. PPs and the concomitant [Ca2+]i elevations were significantly reduced in amplitude and duration by LY379268. The mGlu-mediated inhibitory effect on PPs was mimicked by ω-Aga-IVA, suggesting an involvement of P-type channels. Moreover, electrically induced ACh release from striatal slices was reduced by mGlu2 receptor agonists and occluded by ω-Aga-IVA in a dose-dependent manner. Finally, double-labeling experiments combining mGlu2 receptor in situ hybridization and choline acetyltransferase immunocytochemistry revealed a strong mGlu2 receptor labeling on cholinergic interneurons, whereas single-label isotopic in situ hybridization for mGlu3 receptors did not show any labeling in these large striatal interneurons. These results suggest that the mGlu2 receptor-mediated modulatory action on cell excitability would tune striatal ACh release, representing an interesting target for pharmacological intervention in basal ganglia disorders.