Jun, Fos and Krox in the thalamus after C-fiber stimulation: Coincident-input-dependent expression, expression across somatotopic boundaries, and nucleolar translocation

Expression of the inducible transcription factors Jun. Fos and Krox is comm only used to map neurons in the brain that are activated by sensory inputs. However, some neurons known to be electrically excited by such inputs do n ot always express these factors. In particular, stimulation of hindlimb sen sory nerve C-fibers induces expression of c-Fos in the medial thalamus (the mediodorsal, intermediodorsal, centrolateral and centromedial), but not in the lateral thalamus (the ventroposterolateral, ventroposteromedial and po sterior group). We hypothesized that c-Fos expression might only occur in t hese lateral areas after more complex stimulation patterns, or that only ot her transcription factors can be induced in these areas by such stimuli. Th us we examined the effects of single, repeated and coincident C-fiber input s on expression of six inducible transcription factors in the medial, later al and reticular thalamus of the rat. A weak C-fiber input caused by noxiou s mechanical stimulation of the skin of one hindpaw did not induce expressi on of c-Fos, FosB, Krox-20 or Krox-24: but it did reduce the basal expressi ons of c-Jun and JunD in both the medial and lateral areas. An intense inpu t produced by electrical stimulation of all the C-fibers in one sciatic ner ve also failed to induce expression of c-Fos, FosB, Krox-20 or Krox-24 in t he medial or lateral areas. However. in the medial thalamus it increased c- Jun and reduced the basal expression of JunD. whereas in the lateral thalam us it had no effect on c-Jun but again reduced the basal expression of JunD . With repeated stimulation, i.e. when the noxious stimulus was applied to the contralateral hindpaw 6 h after the sciatic stimulation, there was agai n no induction of c-Fos, FosB or Krox-20 in the medial thalamus: but there was an increase in c-Jun and Krox-24. and a decrease in JunD levels. In the lateral thalamus the repeated stimulation again failed to induce c-Fos. bu t the expressions of FosB, c-Jun and Krox-24 were increased, and that or Ju nD was again reduced. With coincident stimulation, i.e. when a stimulus was applied to each hindpaw simultaneously, c-Fos and Krox-24 remained absent: but there was a marked induction of FosB and Krox-20, a strong repression of c-Jun, and no effect or a reduction of the basal levels of JunD. This co incident stimulation also caused FosB to appear in the nucleolus of many th alamic neurons. MK-801. but not L-NAME, blocked all these changes. In summary, noxious stimulation affects the expression of all transcription factors in the medial. lateral and reticular thalamus in a complex manner depending upon the inducible transcription factor considered, the thalamic nucleus, and the stimulation paradigm. The expression of some transcription factors uniquely after simultaneous inputs suggests they act as coincidenc e detectors at the gene level. (C) 2001 IBRO. Published by Elsevier Science Ltd. All rights reserved.