Neuroanatomical and functional characterization of ghrelin receptor expressing neurons of the nucleus of the solitary tract in a transgenic mouse model

DE FRANCESCO PN; CORNEJO MP; KOC V; PADIN ME; GARCIA ROMERO G; REYNALDO M; PERELLO M

Ciudad Autónoma de Buenos Aires

Congreso; 2nd FALAN Congress; 2016

The nucleus of the solitary tract (NST) is a major sensory nucleus in the dorsal medulla that receives cardiovascular, visceral, respiratory, gustatory, and orotactile information. It takes part in the integrative role of the dorsal vagal complex, which regulates food intake and relays autonomic neural circuits controlling key functions such as glucaemia, blood pressure and gastro-intestinal motility. The NST is known to have neurons that express the growth hormone secretagogue receptor (GHSR), the target of the hormone ghrelin, but their identification is challenging.To overcome this issue, we used a transgenic mouse line in which green fluorescent protein (GFP) is under the control of the GHSR promoter (GHSR-GFP mice). This allowed us to perform a detailed neuroanatomical description as well as a functional exploration of the GHSR-expressing neurons in the NST.GHSR neurons presented a widespread rostrocaudal distribution along the NST, but preferentially forming two clusters within the rostral and the posterior regions. An immunophenotypic analysis of these neurons revealed they are negative for M-enk, TH, NPY, TRH, ChAT and GAD-67.Using c-Fos as a marker of neuronal activation we explored the response of these neurons by exposing GHSR-GFP mice to different experimental paradigms known to activate this region: a 48h fasting protocol, a vaseline gavage protocol, a 24h water deprivation protocol, i.p. LiCl administration, i.p. hypertonic NaCl administration, oral sucrose administration, and a high-fat diet binge protocol. Of all these procedures, only the former protocol showed a significant increase of c-Fos expression in GHSR neurons within the NST, suggesting their direct involvement in specific responses related to this paradigm.