Excitation of neurons results in a series of finely orchestrated responses that occur over a time frame ranging from fractions of a second to hours or days. In the short term, stimulation evokes an array of biochemical and biophysical events that represent the execution of the neurophysiological phenotype of a particular cell. These processes, which contribute to the overall behavior of a neural circuit, do not require de novo protein synthesis. In contrast, stimulation is also linked to long-term phenotypic changes that require alterations in gene expression. Thus, one or more mechanisms must exist that couple cell-surface stimuli to the transcriptional regulatory apparatus of the neuron. In this article James Morgan and Tom Curran detail a stimulus-transcription coupling cascade, involving the products of the proto-oncogenes, c-fos and c-jun, that operates in many cell types including neurons.