Association between the low threshold calcium spike and activation of NMDA receptors in guinea-pig substantia nigra pars compacta neurons

The aim of this study was to examine the interaction between N-methyl-D-aspartate (NMDA) receptor activation and the low threshold calcium spike (LTS) of phasically firing neurons in the rostral part of the substantia nigra pars compacta (SNpc) in mid-brain slices. Bath perfusion of 10 mu M NMDA gradually increased the LTS area and the effect reached a maximum after 6 min of perfusion. This enhancement of the LTS by NMDA was blocked both by a competitive and non-competitive NMDA receptor antagonist, 50 mu M D-AP5 and 10 mu M MK801, respectively, demonstrating that this effect of NMDA was mediated through NMDA receptors. Prolonged exposure to increasing concentrations of NMDA (0.1-100 mu M) progressively decreased the LTS area. The higher doses led to an irreversible marked depolarization and decrease of the membrane resistance. These results suggest that the LTS of SNpc neurons can trigger a NMDA receptor-dependent response which may have physiological and pathological roles.