Jun, Fos and Krox in the hippocampus after noxious stimulation: Simultaneous-input-dependent expression and nuclear speckling

Stimulation of sensory C-fibres produces extensive expression of the Fos, Jun and Krox families of inducible transcription factors (ITFs) in many nociceptive CNS areas [28]. In the hippocampus, however, c-Fos is only weakly induced by such stimulation, and expression of the other ITFs has not been studied. Here we examine the effects of single, repeated and simultaneous C-fibre inputs on ITF expressions in the rat hippocampus. A brief, strong electrical stimulation of sciatic nerve C-fibres induced little or no expression of c-Fos or Krox-20. In contrast, FosB was induced and continued to rise in all areas, whereas the basal expressions of c-Jun and Krox-24 were initially reduced but then returned during the subsequent 36 h. A weak noxious cutaneous stimulus applied to one hindpaw induced only weak expressions of the ITFs. However, if the sciatic stimulation was applied contralaterally and 6 h beforehand, this weak stimulus strongly induced Krox-24, but not other ITFs, i.e. there was a potentiation of Krox-24 expression. When these two stimuli were applied simultaneously a few c-Fos labelled cells did appear, and there was and an increased Krox-24 expression. There was also a strong potentiation of FosB and a strong reduction in c-Jun expression. This simultaneous stimulation was the only type of stimulation to induce expression of Krox-20. Also after simultaneous stimulation the majority of the nuclear labelling for FosB, but not of the other ITFs, had a speckled appearance. MK-801 blocked these changes in ITF expressions, but it could also cause the C-fibre stimulations to induce c-Fos and c-Jun in specific areas of the hippocampus. Thus C-fibre stimulation does affect transcription factor activity in the hippocampus; and the strong responses of some ITFs to simultaneous inputs points to their having a role as 'genetic coincidence detectors' in the hippocampus.