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.
School of Biomedical and Biomolecular Sciences, Griffith University, Nathan, Australia.
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D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*; D018891:Dentate Gyrus / Q000166:cytology / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D017874:Immediate-Early Proteins; D007150:Immunohistochemistry; D008297:Male; D009412:Nerve Fibers / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D009475:Neurons, Afferent / Q000737:chemistry / Q000378:metabolism; D009676:Noxae; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000096:biosynthesis*; D016755:Proto-Oncogene Proteins c-jun / Q000032:analysis / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000166:cytology / Q000502:physiology; D014157:Transcription Factors / Q000032:analysis / Q000096:biosynthesis*
D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486110:Egr1 protein, rat; C497328:Egr2 protein, rat; D018691:Excitatory Amino Acid Antagonists; D017874:Immediate-Early Proteins; D009676:Noxae; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D016291:Dizocilpine Maleate