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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)-alpha-amino-3-hydroxy-5- methylisoxazole-4-propionate (AMPA) or the GABAA 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 microM) 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 microM 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.

Following microinjection into the nucleus tractus solitarius (NTS), the effects of glutamate on the baroreceptor reflex are poorly antagonized by kynurenic acid and DL-2-amino-5-phosphonovaleric acid, suggesting the possible involvement of metabotropic glutamate receptors in this response. The metabotropic glutamate receptor agonist 1S,3R-1- aminocyclopentane-1,3-dicarboxylic acid (1S,3R-ACPD) depolarized neurons located medial to the tractus solitarius (TS) at the level of the area postrema in coronal sections of the rat NTS. This effect was mimicked by glutamate and was not blocked by antagonists at alpha-amino- 3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA)/kainate or NMDA receptors. 1S,3R-ACPD also produced an inward current under voltage clamp that was not accompanied by a rise in [Ca2+]i, monitored with the Ca(2+)-sensitive dye fura-2. Conversely, the muscarinic agonist carbachol produced an outward current and a rise in [Ca2+]i. 1S,3R-ACPD reduced both the excitatory and the inhibitory postsynaptic current resulting from single electrical stimuli in the region of the TS. High- frequency stimulation of the TS produced an inward current in the presence of AMPA/kainate and NMDA receptor blockers. This current had similar properties to that produced by 1S,3R-ACPD. Thus, metabotropic glutamate receptors may mediate a component of excitatory transmission in the NTS.