Presynaptic effects of NMDA in cerebellar Purkinje cells and interneurons

NMDA receptors (NMDARs) are generally believed to mediate exclusively posts ynaptic effects at brain synapses. Here we searched for presynaptic effects of NMDA at inhibitory synapses in rat cerebellar slices. In Purkinje cells , application of NMDA enhanced the frequency of miniature IPSCs (mIPSCs) bu t not that of miniature EPSCs (mEPSCs). This increase in frequency was depe ndent on the external Mg2+ concentration. In basket and stellate cells, NMD A induced an even larger mIPSC frequency increase than in Purkinje cells, w hereas mEPSCs were again not affected. Moreover, NMDA induced an inward cur rent in both types of interneuron, which translated into a small depolariza tion (similar to 10 mV for 30 mu M NMDA) under current-clamp conditions. In paired recordings of connected basket cell-Purkinje cell synapses, depolar izations of 10-30 mV applied to the basket cell soma enhanced the frequency of postsynaptic mIPSCs, suggesting that somatic depolarization was partial ly transmitted to the terminals in the presence of tetrodotoxin. However, t his effect was small and unlikely to account fully for the effects of NMDA on mIPSCs. Consistent with a small number of dendritic NMDARs, evoked EPSCs in interneurons had a remarkably small NMDA component. Evoked IPSCs at int erneuron-interneuron synapses were inhibited by NMDA, and the rate of failu res was increased, indicating again a presynaptic site of action. We conclu de that activation of NMDARs in interneurons exerts complex presynaptic eff ects, and that the corresponding receptors are most likely located in the a xonal domain of the cell.