Hippocampal ghrelin signalling informs the decision to eat

Hunger is an internal state that not only invigorates behaviour towards feeding, but also acts as a contextual cue for the higher-order control of anticipatory feeding-related behaviour. The ventral hippocampus is a brain region important in encoding context, but how internal contexts such as hunger are represented in hippocampal circuits is not known. Pyramidal neurons in the ventral hippocampus, and in particular within the ventral CA1/subiculum border (vS) express the receptor for the peripheral hunger hormone ghrelin, and ghrelin is known to cross the blood brain barrier and directly influence hippocampal circuitry. However, what role vS neurons play during feeding related behaviour, and how ghrelin influences this role has not been directly investigated. In this study, we used a combination of whole-cell electrophysiology, optogenetics and molecular knockdown together with in vivo calcium imaging in mice to investigate the role of vS during feeding behaviour across different states of hunger. We found that activity of a unique subpopulation of vS neurons that project to the nucleus accumbens (vS-NAc) were active specifically when animals approached and investigated food, and that that this activity inhibited the transition to begin eating. Increases in peripheral ghrelin reduced vS-NAc activity during this anticipatory phase of feeding behaviour, by increasing the influence of synaptic inhibition. Furthermore, this effect required postsynaptic GHSR1a expression in vS-NAc neurons, suggesting a direct role of ghrelin signalling. Consistent with this role of hippocampal ghrelin signalling, removal of GHSR1a from vS-NAc neurons impaired ghrelin-induced changes in feeding-related behaviour. Together, these experiments define a ghrelin-sensitive hippocampal circuit that informs the decision to eat based on internal state. ### Competing Interest Statement The authors have declared no competing interest.