Ghrelin receptor signaling targets segregated clusters of neurons within the nucleus of the solitary tract

CORNEJO MP; DE FRANCESCO PN; GARCIA ROMERO G; PORTIANSKY EL; ZIGMAN JM; REYNALDO M; PERELLO M

San Diego

Congreso; Neuroscience 2018 (SfN); 2018

Society for Neuroscience

Ghrelin is a stomach-derived peptide hormone and its receptor, the growth hormone secretagogue receptor (GHSR) is highly expressed in the brain. The nucleus of the solitary tract (NTS) is a major sensory nucleus in the dorsal medulla that receives cardiovascular, visceral, gustatory and orotactile information. NTS neurons express GHSR but the identity and the physiological role of GHSR-expressing neurons of the NTS are uncertain. In this study, we used a GHSR reporter mouse (GHSR-eGFP) to perform a detailed neuroanatomical and functional characterization of GHSR-expressing neurons of the NTS. We first mapped the neuroanatomical distribution of eGFP neurons within the NTS. Then, we explored the phenotype of eGFP neurons using IHC against different neuronal populations. We also explored the physiological role of GHSR-expressing neurons of the NTS exposing GHSR-eGFP animals to experimental protocols known to activate the NTS and to involve ghrelin signaling and examining the pattern of expression of c-Fos in eGFP positive cells. Overall, we found that GHSR-expressing neurons were located throughout the extension of the NTS forming three clusters: one pair of rostral clusters, mostly comprising the ventral subnucleus, and one caudal cluster, mostly involving the parvicellular subnucleus. We also found that a population of GHSR-expressing neurons is GABAergic. Finally, eGFP neurons of the rostral clusters of the NTS showed an increase in c-Fos in response to hyperphagic protocols, while the caudal cluster of eGFP cells increased c-Fos levels in response to sensory stimuli from the gastrointestinal tract. Our results indicate that ghrelin signaling targets segregated clusters of NTS neurons that respond to different stimuli depending on their location.