SIGNALING FROM SYNAPSE TO NUCLEUS - POSTSYNAPTIC CREB PHOSPHORYLATIONDURING MULTIPLE FORMS OF HIPPOCAMPAL SYNAPTIC PLASTICITY

Phosphorylation of the transcription factor CREB is thought to be impo rtant in processes underlying long-term memory. It is unclear whether CREB phosphorylation can carry information about the sign of changes i n synaptic strength, whether CREB pathways are equally activated in ne urons receiving or providing synaptic input, or how synapse-to-nucleus communication is mediated. We found that Ca2+-dependent nuclear CREB phosphorylation was rapidly evoked by synaptic stimuli including, but not limited to, those that induced potentiation and depression of syna ptic strength. In striking contrast, high frequency action potential f iring alone failed to trigger CREB phosphorylation. Activation of a su bmembranous Ca2+ sensor, just beneath sites of Ca2+ entry, appears cri tical for triggering nuclear CREB phosphorylation via calmodulin and a Ca2+/calmodulin-dependent protein kinase.