NFAT-dependent gene expression in the nervous system: A critical mediator of neurotrophin-induced plasticity

The modulation of synaptic transmission in response to particular spatial and temporal patterns of neuronal firing provides a means by which information can be stored within the nervous system. Activity-dependent synaptic plasticity is thought to underlie such diverse processes as the regulation and refinement of neuronal connections during development, learning and memory within the adult brain, and persistent pain states incurred following tissue injury and inflammation. While acute changes in synaptic strength are accomplished through modulation of existing proteins that influence cellular excitability, enduring modifications require the induction of gene expression and protein synthesis. Therefore, understanding the molecular mechanisms by which transcription factors bridge signaling at the synapse to gene expression in the nucleus is of particular importance. Recent evidence suggests that the NFATc family of transcription factors plays an important role in neuronal activity-dependent gene expression. This chapter reviews these data, focusing on activation of NFAT-dependent transcription by neurotrophins, signaling molecules involved in many aspects of neuronal development and plasticity.