POTENTIATION OF EXCITATORY POSTSYNAPTIC POTENTIALS BY A METABOTROPIC GLUTAMATE-RECEPTOR AGONIST (1S,3R-ACPD) IN FROG SPINAL MOTONEURONS

We conducted intracellular recordings of lumbar motoneurons in the arterially-perfused frog spinal cord and investigated the effects of a metabotropic glutamate receptor agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), on excitatory postsynaptic potentials evoked by stimulation of the descending lateral column fibers (LC-EPSPs). in the absence of Mg2+, ACPD reversibly potentiated the amplitude of monosynaptic LC-EPSPs by more than 15% in 15 of 19 cells with 5 mu M ACPD and in 7 of 12 cells with 0.5 mu M ACPD. The EPSP amplitudes with 5 and 0.5 mu M ACPD were 142 +/- 10% (mean +/- S.E.M., n = 19) and 130 +/- 13% (n = 12) of the controls. The potentiation was seen without a decrease in the input conductance. Glutamate-induced depolarizations in the absence and the presence of 0.5 mu M ACPD were not significantly different in cells perfused with the low Ca2+-high Mg2+ solution which eliminated chemical transmission. Paired pulse facilitation of LC-EPSPs was reversibly decreased in association with the potentiation. ACPD-induced potentiation of monosynaptic LC-EPSPs was seen in 5 of 6 cells in the presence of D-(-)-2-amino-5-phosphonopentanoic acid (D-AP5), an NMDA receptor antagonist. ACPD occasionally activated polysynaptic components of LC-EPSPs which were mediated mainly via NMDA receptors. On the other hand, ACPD-induced potentiation of EPSPs was inhibited by extracellular Mg2+. Five mu M ACPD potentiated monosynaptic EPSPs in 4 of 6 cells with 1 mM Mg2+ in the solution and in 2 of 17 cells with 4 mM Mg2+, and the EPSP amplitude was 123 +/- 9% (n = 6) and 98 +/- 3% (n = 17) of those before application of ACPD, respectively. These results suggest that activation of metabotropic glutamate receptors potentiates LC-EPSPs via mechanisms sensitive to Mg2+ and may work as a positive feedback mechanism at the excitatory amino acid-mediated synapses between the descending fibers and lumbar spinal motoneurons.