Fig. 4.

Activation of the transcription factor CREB by the NMDA signal transduction pathway. Activation of NMDA receptors causes Ca^{2 +} influx (A). Ca^{2 +} interacts with kinases and phosphatases that act as messengers in signal transduction pathways. Kinases and phosphatases alter the phosphorylation patterns of TFs and, thus, influence their ability to stimulate the synthesis of mRNA. For example, CaM kinases, activated by Ca^{2 +}, can translocate to the nucleus and phosphorylate the TF CREB (Bito et al., 1996; Sheng et al., 1991; Sun et al., 1994). Phosphorylated CREB stimulates the synthesis of many different mRNAs, which are translated into proteins. These proteins alter neuronal properties and contribute to memory formation and synaptic strength. For instance, the newly synthesized proteins are incorporated into synapses. An active synapse can increase in size, and may even split into two synapses (B). An inactive synapse can decrease in size and may be even disassembled (C). PSD, postsynaptic density.