Differential regulation of fos family genes in the ventrolateral and dorsomedial subdivisions of the rat suprachiasmatic nucleus

Extensive studies have established that light regulates c-fos gene expressi on in the suprachiasmatic nucleus, the site of an endogenous circadian cloc k, but relatively little is known about the expression of genes structurall y related to c-Sos, including fra-1, fra-2 and fosB. We analysed the photic and temporal regulation of these genes at the messenger RNA and immunoreac tive protein levels in rat suprachiasmatic nucleus, and we found different expression patterns after photic stimulation and depending on location in t he ventrolateral or dorsomedial subdivisions. In the ventrolateral suprachi asmatic nucleus, c-fos, fra-2 and fosB expression was stimulated after a su bjective-night (but not subjective-day) light pulse. Expression of the fra- 2 gene was prolonged following photic stimulation, with elevated messenger RNA and protein levels that appeared unchanged for at least a few hours bey ond the c-fos peak. Unlike c-fos and fra-2, the fosB gene appeared to be ex pressed constitutively in the ventrolateral suprachiasmatic nucleus through out the circadian cycle; immunohistochemical analysis suggested that Delta FosB was the protein product accounting for this constitutive expression, w hile FosB was induced by the subjective-night light pulse. In the dorsomedi al suprachiasmatic nucleus, c-fos and fra-2 expression exhibited an endogen ous circadian rhythm, with higher levels during the early subjective day, a lthough the relative abundance was much lower than that measured after ligh t pulses in the ventrolateral suprachiasmatic nucleus. Double-label immunoh istochemistry suggested that some of the dorsomedial cells responsible for the circadian expression of c-Fos also synthesized arginine vasopressin. No evidence of suprachiasmatic nucleus fra-1 expression was found. In summary, fos family genes exhibit differences in their specific expressi on patterns in the suprachiasmatic nucleus, including their photic and circ adian regulation in separate cell populations in the ventrolateral and dors omedial subdivisions. The data, in combination with our previous results [T akeuchi J. et al. (1993) Neuron 11, 825-836], suggest that activator protei n-1 binding sites on ventrolateral suprachiasmatic nucleus target genes are constitutively occupied by Delta FosB/JunD complexes, and that c-Fos, Fra- 2, FosB and JunB compete for binding after photic stimulation. The differen tial regulation of fos family genes in the ventrolateral and dorsomedial su prachiasmatic nucleus suggests that their circadian function(s) and downstr eam target(s) are likely to be cell specific. (C) 2000 IBRO. Published by E lsevier Science Ltd. All rights reserved.