Regulation and function of immediate-early genes in the brain: beyond neuronal activity markers

Long lasting forms of synaptic plasticity and long-term memory formation require new mRNA and protein synthesis. While activity-dependent expression of immediate-early genes has long been thought to account for such critical de novo macromolecular synthesis, experimental proof has been scarce until recently. During the past few decades, a growing number of genetic and molecular biological studies have started to elucidate essential roles of immediate-early genes in synaptic plasticity and cognitive functions. I here present an overview of the history and recent work on regulation and function of neuronal immediate-early genes, including Arc/arg3.1. This review provides a conceptual framework in which various immediate-early genes underlie several distinct processes required for long-term synaptic changes and memory formation.