C-fos and c-jun in the paraventricular nucleus play a role in regulating peptide gene expression, oxytocin and glutamate release, and maternal behaviour

In sheep, birth leads to the induction of maternal behaviour through brain oxytocin release. Associated with these events is an upregulation of oxytocin, opioid and corticotrophin-releasing hormone (CRH) gene expression, as well as that of the immediate early gene c-fos in the paraventricular nucleus (PVN) of the hypothalamus. We investigated the role of c-fos dimerizing with c-jun in controlling the induction of maternal behaviour, altered peptide gene expression, and oxytocin and amino acid release in this region at birth. Fluorescence-labelled antisense oligodeoxyribonucleotides (ODNs) against c-fos/c-jun were infused bilaterally in the PVN, via microdialysis probes with 100 kDa cut-off membranes, and were incorporated into 50-60% of the cells. Compared with the control (scrambled) sequences, they significantly reduced basal concentration of glutamate (to 31.7% of baseline after 10 h) and prevented birth-induced release of aspartate. In addition, antisense treatment reduced the birth-induced increase in oxytocin concentration in the PVN, but not in blood. Although all the animals were fully maternal, the antisense treatment did reduce the peak expression of two components of maternal behaviour: low-pitched bleats; and lamb sniffing. Finally, in situ hybridization histochemistry revealed that the antisense treatment significantly reduced the birth-induced upregulation of c-fos, oxytocin, CRH and preproenkephalin mRNA expression in the PVN, whilst not affecting that of arginine vasopressin. These results suggest that c-fos/c-jun transcription factors play a role in the birth-induced upregulation of oxytocin, CRH and preproenkephalin gene expression, as well as on glutamate and oxytocin release in the sheep PVN.