TY - JOUR
T1 - Growth hormone secretagogue receptor signaling in the supramammillary nucleus targets nitric oxide-producing neurons and controls recognition memory in mice
AU - Aguggia, Julieta P.
AU - Cornejo, María P.
AU - Fernandez, Gimena
AU - De Francesco, Pablo N.
AU - Mani, Bharath Kumar
AU - Cassano, Daniela
AU - Cabral, Agustina
AU - Valdivia, Spring
AU - García Romero, Guadalupe
AU - Reynaldo, Mirta
AU - Fehrentz, Jean Alain
AU - Zigman, Jeffrey M.
AU - Perello, Mario
N1 - Funding Information:
We would like to thank to Josefina Lacunza, Lucas Aguilar and Maria Jose Tolosa for their technical assistance. This work was supported by grants from the Fondo para la Investigaci?n Cient?fica y Tecnol?gica (FONCyT, PICT2016?1084, PICT2017?3196 and PICT2019?3054) and from CONICET (PUE-2017) to MP.
Funding Information:
We would like to thank to Josefina Lacunza, Lucas Aguilar and Maria Jose Tolosa for their technical assistance. This work was supported by grants from the Fondo para la Investigación Científica y Tecnológica (FONCyT, PICT2016–1084, PICT2017–3196 and PICT2019–3054) and from CONICET (PUE-2017) to MP.
Publisher Copyright:
© 2022 Elsevier Ltd
PY - 2022/5
Y1 - 2022/5
N2 - Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.
AB - Ghrelin is a stomach-derived hormone that acts via the growth hormone secretagogue receptor (GHSR). Recent evidence suggests that some of ghrelin's actions may be mediated via the supramammillary nucleus (SuM). Not only does ghrelin bind to cells within the mouse SuM, but ghrelin also activates SuM cells and intra-SuM ghrelin administration induces feeding in rats. In the current study, we aimed to further characterize ghrelin action in the SuM. We first investigated a mouse model expressing enhanced green fluorescent protein (eGFP) under the promoter of GHSR (GHSR-eGFP mice). We found that the SuM of GHSR-eGFP mice contains a significant amount of eGFP cells, some of which express neuronal nitric oxide synthase. Centrally-, but not systemically-, injected ghrelin reached the SuM, where it induced c-Fos expression. Furthermore, a 5-day 40% calorie restriction protocol, but not a 2-day fast, increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice, whereas c-Fos induction by calorie restriction was not observed in GHSR-deficient mice. Exposure of satiated mice to a binge-like eating protocol also increased c-Fos expression in non-eGFP+ cells of the SuM of GHSR-eGFP mice in a GHSR-dependent manner. Finally, intra-SuM-injected ghrelin did not acutely affect food intake, locomotor activity, behavioral arousal or spatial memory but increased recognition memory. Thus, we provide a compelling neuroanatomical characterization of GHSR SuM neurons and its behavioral implications in mice.
KW - Behavior
KW - Ghrelin receptor
KW - Hypothalamus
KW - Memory
KW - Reward
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UR - http://www.scopus.com/inward/citedby.url?scp=85126104726&partnerID=8YFLogxK
U2 - 10.1016/j.psyneuen.2022.105716
DO - 10.1016/j.psyneuen.2022.105716
M3 - Article
C2 - 35290931
AN - SCOPUS:85126104726
SN - 0306-4530
VL - 139
JO - Psychoneuroendocrinology
JF - Psychoneuroendocrinology
M1 - 105716
ER -