Multi-determinate regulation of neuronal survival: neuropeptides, excitatory amino acids and bioelectric activity

Neuronal survival of dorsal root ganglion-spinal cord cultures was determined after treatment with vasoactive intestinal peptide (VIP) and an antagonist to the N-methyl-D-aspartate receptor (NMDA). Blockade of NMDA receptors with 2-amino 5-phosphonovaleric acid (AP5) produced a biphasic response on neuronal survival: low concentrations (0.1 microM) resulting in greater survival and higher concentrations (100 microM) causing cell death. VIP, a substance with demonstrated neurotrophic properties in vitro, prevented the neuronal cell death associated with high concentrations of AP5, while having no additive effect on the survival-promoting action of low levels of AP5. Electrophysiological studies indicated that AP5, although reducing high frequency bursting activity, did not significantly reduce the abundant on-going asynchronous activity present in these cultures of high density neuronal networks. These data indicate that excitatory amino acids have more than one action that can influence neuronal survival during development and that VIP can increase neuronal survival in bioelectrically active cultures when NMDA channels are blocked. Together with previous studies, these data suggest that multiple neurochemical inputs serve to determine the survival of spinal cord neurons during development, perhaps through one final common pathway: intracellular calcium regulation.