Glutamate-induced inhibition of paired pulse facilitation of monosynaptic excitatory post-synaptic potentials in frog spinal motoneurons

Abstract

To evaluate actions of glutamate on excitatory synaptic transmission in the central nervous system, we examined glutamate-induced changes in the paired pulse facilitation of monosynaptic excitatory post-synaptic potentials evoked by stimulation of the lateral column fibers (LC-EPSPs) on lumbar motoneurons in the frog spinal cord. Glutamate (1 mM) depolarized motoneurons both in the presence and absence of Mg 2+. In most cells perfused with Mg 2+-free or high Ca 2+-Mg 2+ solutions, the glutamate potential was accompanied by a reduction in pak amplitude of EPSPs, although the degree of change varied with the cells. Glutamate enhanced the EPSP amplitude in a few cells with Mg 2+-free and high Ca 2+-Mg 2+ solutions, and in most cells with high Mg 2+ medium. In 3/5 cells tested, the paired pulse facilitation of EPSPs was reduced by glutamate when the EPSP amplitude either increased or decreased. NMDA (50 μM), kainate (50–100 μM), quisqualate (5–50 μM) and l-2-amino-4-phosphonobutyrate ( l-AP4, 1 mM) also decreased the facilitation in about half of the cells tested. The glutamate-induced decrease in the facilitation was observed in both the presence and absence of Mg 2+ and was not affected by the concomitant application of glutamate and antagonists for non-NMDA or NMDA receptors, such as 6-cyano-7-nitro-quinoxalinediones (CNQX, 60 μM) or 2-amino-5-phosphonovalerate (APV, 250 μM). Glutamate reduced the facilitation of excitatory post-synaptic currents (EPSCs) recorded at a constant membrane potential under voltage clamp, when the EPSC amplitude either increased or decreased and when the input conductance either increased or decreared. Thus changes in membrane potential or input conductance of the post-synaptic membrane were not essential to the glutamate-induced inhibition of the facilitation. These results suggest that glutamate modulates release of excitatory transmitters via mechanisms insensitive to Mg 2+, CNQX and APV.