NEURONS respond to extracellular stimulation by modulating the express
ion 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 thes
e 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 rec
ognized two major drawbacks of ITFs that limit their use in the CNS: c
ell-type expression specificity and stimulus-transcription coupling un
certainty. In this review, I discuss recent advances in the field that
broaden our understanding of the molecular constraints on ITF express
ion as well as in techniques that may help to extend their utility in
functional mapping.