Group II metabotropic glutamate receptor modulation of excitatory transmission in rat subthalamic nucleus

Patch pipettes were used to record currents in whole-cell configuration to study the effects of group II metabotropic glutamate receptor (mGluR) stimulation on synaptic transmission in slices of rat subthalamic nucleus. Evoked glutamatergic excitatory postsynaptic currents (EPSCs) were reversibly reduced by the selective group II mGluR agonist (2'S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine (DCG IV) in a concentration-dependent manner, with an IC50 Of 0.19 +/- 0.05 muM. DCG IV (1 mum) had no effect on inhibitory postsynaptic currents mediated by GABA. DCG IV-induced inhibition of EPSCs was reversed by the selective group II mGluR antagonist LY 341495 (100 nM) and mimicked by another selective group II agonist (2S,1'S,2'S)-2-(carboxycyclopropyl)glycine (L-CCG-1). Inhibition of EPSC amplitude by DCG IV and L-CCG-1 was associated with an increase in the paired-pulse ratio of EPSCs. The protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (2 muM) reduced the inhibitory effect of DCG IV on EPSCs. However, the response to DCG IV was not affected by the protein kinase A (PKA) activator forskolin (20 muM), by the adenylyl cyclase inhibitor MDL 12230A (20 muM), or by the phosphodiesterase inhibitor Ro 20-1724 (50 muM). DCG IV-induced inhibition of EPSCs was reduced by the non-selective protein kinase inhibitors H-7 (100 muM), H-8 (50 muM) and HA-1004 (100 muM). These results suggest that group II mGluR stimulation acts presynaptically to inhibit glutamate release by a PKC-dependent mechanism in the subthalamic nucleus.