N-methyl-D-aspartate receptors influence neuronal survival in developing spinal cord cultures

Neuronal cell death, which exhibits precise spatial and temporal regulation, serves to remodel and optimize function in the developing nervous system. The mechanisms underlying neuronal cell death are poorly understood, but electrical activity and trophic substances appear to be among the important determinants of survival. We find that N-methyl-D-aspartate (NMDA) receptor antagonists induce neuronal cell death in developing spinal cord cultures. The magnitude of cell death is similar in amount to that produced by blocking action potentials with tetrodotoxin (TTX). The NMDA antagonists and TTX accelerate neuronal death in 2-week-old cultures but not in those that are 1 month old. Low concentrations of NMDA increased neuronal survival under conditions of electrical blockade with TTX. In addition, treatment with low levels of a calcium ionophore also decreased cell death associated with TTX. These results suggest that the NMDA receptor is an important determinant of neuronal survival and that this influence is stage-dependent and likely to be calcium-mediated.