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, J un and Krox families of inducible transcription factors (ITFs) in many noci ceptive CNS areas [28]. In the hippocampus, however, c-Fos is only weakly i nduced by such stimulation, and expression of the other ITFs has not been s tudied. Here we examine the effects of single, repeated and simultaneous C- fibre inputs on ITF expressions in the rat hippocampus. A brief, strong ele ctrical stimulation of sciatic nerve C-fibres induced little or no expressi on 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 init ially 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 a nd 6 h beforehand, this weak stimulus strongly induced Krox-24, but not oth er ITFs, i.e, there was a potentiation of Krox-24 expression. When these tw o 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 stron g potentiation of FosB and a strong reduction in c-Jun expression. This sim ultaneous stimulation was the only type of stimulation to induce expression of Krox-20. Also after simultaneous stimulation the majority of the nuclea r 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 t he C-fibre stimulations to induce c-Fos and c-Jun in specific areas of the hippocampus. Thus C-fibre stimulation does affect transcription factor acti vity in the hippocampus; and the strong responses of some ITFs to simultane ous inputs points to their having a role as 'genetic coincidence detectors' in the hippocampus. (C) 2001 Elsevier Science B.V. All rights reserved.