In the central nervous system, long-term adaptive responses to changes in the environment, such as the processes involved in learning and memory, require the conversion of extracellular stimuli into intracellular signals. Many of these signals involve the induction of gene expression. The late, transcription- and translation-dependent phase of long-term synaptic potentiation (L-LTP) is an attractive cellular model for long-lasting memory formation. The transcription factor cAMP response element-binding protein (CREB) plays an essential role in the maintenance of L-LTP. However, how synaptic signals propagate to the nucleus to initiate CREB-target gene expression is unclear. Recent studies indicate that the CREB transducer of regulated CREB activity 1 coactivator undergoes neuronal activity-dependent translocation from the cytoplasm to the nucleus, a process required for CRE-dependent gene expression and the maintenance of L-LTP in the hippocampus.