Quisqualate and N-methyl-d-aspartate synergistically excite cerebellar Purkinje cells as a long-term effect

Interactions between the excitatory amino acids (EAAs) quisqualate (QUIS) and N-methyl-d-aspartate (NMDA) were investigated in order to explore mechanisms which may help to explain long-term changes in synaptic efficacy induced by these agents. In 93% of the cerebellar Purkinje (Pnj) cells recorded extracellularly which responded to iontophoretic application of QUIS with increases in discharge of up to 100% above spontaneous levels, NMDA administration sensitized the neuron to further QUIS stimulation by 40-200% over control levels of response. NMDA-enhanced QUIS responses reached maximal levels after termination of NMDA application and persisted for up to 2 h post-NMDA. The NMDA receptor blocker 2-amino-5-phosphonovalerate (APV) prevented the observed effect only when administered before but not after NMDA application, suggesting that a long-lasting post-receptor mechanism may be involved in the observed synergistic interaction of QUIS and NMDA.