CREB responsive transcription and memory formation

Abstract

Inhibitors of protein synthesis block memory formation when they are acutely delivered around the time of behavioral training. This requirement for de novo synthesis of proteins includes a prerequisite for gene transcription, since inhibitors of RNA polymerase II display similar effects. These observations, together with the strong biochemical and genetic evidence in Aplysia and Drosophila, led to experiments testing the importance of the cAMP-Response Element (CRE) and its Binding protein (CREB) in long-term memory and synaptic plasticity. In this chapter, we will review the molecular biology of CREB genes, before summarizing the work that demonstrates CREB is an important factor in memory formation. We will then address the more complex issue of why this requirement remains controversial. Drawing from emerging work in Drosophila, we will discuss the complexity of CREB gene expression and how revealing the molecular mechanisms that underlie CREB activity may provide insights and resolutions to the earlier experimental discrepancies.