Neural activity mapping with inducible transcription factors

Neurons respond to extracellular stimulation by modulating the expression of certain immediate-early genes. Inducible transcription factors (ITFs), such as c-Fos and Zif268, are coded by this class of gene and are among the first proteins to appear. The rapid accumulation of these products combined with histological methods that offer detection at the cellular level are key features that have led to their wide use in visualizing activated neurons. However, neuroscientists have long recognized two major drawbacks of ITFs that limit their use in the CNS: cell-type expression specificity and stimulus-transcription coupling uncertainty. In this review, I discuss recent advances in the field that broaden our understanding of the molecular constraints on ITF expression as well as in techniques that may help to extend their utility in functional mapping.