Voltage-sensitivity of motoneuron NMDA receptor channels is modulated by serotonin in the neonatal rat spinal cord

Both N-methyl-D-aspartate (NMDA) and serotonin (5-HT) receptors contribute to the generation of rhythmic motor patterns in the rat spinal cord. Co-app lication of these chemicals is more effective at producing locomotor-like a ctivity than either neurochemical alone. In addition, NMDA application to r at spinal motoneurons, synaptically isolated in tetrodotoxin, induces nonli near membrane behavior that results in voltage oscillations which can be bl ocked by 5-HT antagonists. However, the mechanisms underlying NMDA and 5-HT receptor interactions pertinent to motor rhythm production remain to be de termined. In the present study, an in vitro neonatal rat spinal cord prepar ation was used to examine whether NMDA receptor-mediated nonlinear membrane voltage is modulated by 5-HT. Whole-cell recordings of spinal motoneurons demonstrated that 5-HT shifts the region of NMDA receptor-dependent negativ e slope conductance (RNSC) of the current-voltage relationship to more hype rpolarized potentials and enhances whole-cell inward current. The influence of 5-HT on the RNSC was similar to the effect on the RNSC of decreasing th e extracellular Mg2+ concentration. The results suggest that 5-HT may modul ate this form of membrane voltage nonlinearity by regulating Mg2+ blockade of the NMDA ionophore.