Mitogen-activated protein kinase/extracellular signal-regulated kinase induced gene regulation in brain: a molecular substrate for learning and memory?

The mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) pathway is an evolutionarily conserved signaling cascade involved in a plethora of physiological responses, including cell proliferation, survival, differentiation, and, in neuronal cells, synaptic plasticity. Increasing evidence now implicates this pathway in cognitive functions, such as learning and memory formation, and also in behavioral responses to addictive drugs. Although multiple intracellular substrates can be activated by ERKs, nuclear targeting of transcription factors, and thereby control of gene expression, seems to be a major event in ERK-induced neuronal adaptation. By controlling a prime burst of gene expression, ERK signaling could be critically involved in molecular adaptations that are necessary for long-term behavioral changes. Reviewed here are data providing evidence for a role of ERKs in long-term behavioral alterations, and the authors discuss molecular mechanisms that could underlie this role.