A high number of neurons express c-fos in response to unlimited food intake in fasted rats in the ventral subdivision of the hypothalamic dorsomedial nucleus (DMv). We report here, that in same conditions, limited food consumption failed to induce Fos expression in DMv neurons suggesting that satiation should be one of the important signals that activate of these neurons. The satiation signals from the stomach to the DMv could be transferred in the lower brainstem, especially by glucagon-like peptide-1 (GLP-1)-containing neurons present in the nucleus of the solitary tract (NTS). We demonstrate that GLP-1-immunoreactive fibers and fiber terminals topographically overlap with activated Fos-positive neurons in the DMv of refed rats. Furthermore, the intensity of GLP-1 receptor mRNA signal decreased by fasting and was elevated after refeeding. Using a combination of in situ hybridization histochemistry and immunocytochemistry, we demonstrated GLP-1 receptors in Fos-expressing neurons of the DM. Unilateral transections of ascending GLP-1-containing fibers from the NTS inside the pons in refed rats (unlimited food consumption) resulted in a dramatic decrease in the density of GLP-1 fibers and in the number of Fos-immunoreactive neurons in the DMv, but only on the side of the transection. On the contralateral side to the transection, neither the GLP-1 fiber density nor the number of Fos-positive cells in the DMv changed significantly. Furthermore, the density of GLP-1 immunoreactivity was markedly accumulated in transected nerve fibers caudal to the cut, as a consequence of the interruption of the ascending GLP-1 transport route. These findings suggest that the solitary-hypothalamic projections may represent the neuronal route through GLP-1 neurons of the NTS activate DMv neurons via GLP-1 receptors by conveying information on satiety.

Support was provided by the Hungarian Science Foundation OTKA CK80180 research grant for MP.