Activation of metabotropic glutamate receptors produces reciprocal regulation of ionotropic glutamate and GABA responses in the nucleus of the tractus solitarius of the rat

Whole-cell voltage-clamp recordings were made in thin transverse slices from neurons of the dorsomedial subdivision of the nucleus of the tractus solitarius (NTS) of the rat. Cells were exposed to either the ionotropic glutamate receptor agonist (R,S)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) or the GABA_A receptor agonist muscimol via pressure ejection directed at the cell soma. The metabotropic glutamate receptor agonist 1S,3R-1-aminocyclopentane-1,3-dicarboxylate (1S,3R-ACPD; 2-100 μM) reversibly depressed muscimol-evoked currents. Conversely, 1S,3R-ACPD reversibly potentiated AMPA-evoked currents. High-frequency stimulation of the tractus solitarius in the presence of 6,7-dinitroquinoxaline-2,3-dione and D-2-amino-5-phosphonopentanoic acid also produced a reversible depression of muscimol-evoked currents that was occluded in the presence of 100 μM 1S,3R-ACPD, 8-Br-cGMP or brain-derived natriuretic peptide mimicked the effects of 1S,3R-ACPD on AMPA and muscimol currents. However, agents that mimicked the actions of cAMP or diacylglycerol did not. These findings indicate that metabotropic glutamate receptors may mediate multiple components of excitatory transmission in the NTS including modulation of glutamate and GABA-activated ion channels.