Nuclear localization of TORC1 and cellular co-localization of TORC1 and c-Fos in the visceral neuraxis after systemic LiCl injection

Cyclic–AMP response element binding protein (CREB)-mediated gene expression is critical for the processing of visceral information, including learning about visceral stimuli (e.g. conditioned taste aversion). However, CREB requires additional co-factors to induce gene expression, including transducer of regulated CREB-activity (TORC). The nuclear localization of TORC1 has not been examined previously in the visceral neuraxis. c-Fos, a widely-used marker of activity, is induced by visceral stimulation. If CREB-mediated gene transcription is necessary for c-Fos induction in the visceral neuraxis after systemic LiCl injection, then TORC should be active following stimulation, and co-localized with c-Fos in activated neurons. We examined nuclear (activated) TORC1 in the visceral neuraxis at 30, 60, and 180 minutes after LiCl, as compared to c-Fos induction. Consistent with previous studies we found increases in c-Fos 60 min after LiCl in all regions. Nuclear TORC1 was also increased in the area postrema, NTS, and paraventricular nucleus after LiCl. Surprisingly, in the central amygdala, TORC1 was deactivated after LiCl, such that almost all TORC1 was cytoplasmic, whereas control rats had almost all nuclear TORC1. Fluorescent double-labeling of TORC1 and c-Fos after LiCl found that cellular co-localization of c-Fos and TORC1 was very low across the visceral neuraxis. Nuclear TORC1 expression reveals a population of cells in the visceral neuraxis, independent of c-Fos-positive cells, that are regulated by LiCl. TORC1, and in turn CREB-mediated gene transcription, may not be necessary for c-Fos induction in the visceral neuraxis after LiCl.