Fig. 2.

Intracellular mechanism by which NMDA receptors mediate neuroplasticity and programmed cell death. Upon interaction with glutamate and glycine, NMDA receptor channels open and pass Na ⁺ and Ca^{2 +} ions. The influx of Ca^{2 +} activates signal transduction molecules, such as kinases and phosphatases, which proceed to phosphorylate cellular proteins at the synapse (see insert) and in the nucleus. Among the proteins phosphorylated are TFs that are activated by phosphorylation. These TFs bring RNA polymerase to DNA, which transcribes genes encoded by the DNA into RNA. RNA is shuttled out of the nucleus and translated into protein. The signal transduction pathways activated are specific to the strength of ion influx and the route(s) of ion influx (see insert). The genes induced by these pathways can be involved in either neuroplastic or cell death mechanisms. Insert: At the synapse, Ca^{2 +} entering through NMDA receptors activates local kinases. These kinases phosphorylate/activate neighboring receptors and ion channels, which initiate signal transduction pathways that can combine with the NMDA receptor signal transduction pathway. The combination of receptors and channels activated lends further specificity to the signal transduction pathway, and helps to determine the type of molecular response the neuron will exhibit. P, phosphate residue.