Hippocampal ghrelin signalling informs the decision to eat

Hunger is an internal state that not only invigorates 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 crucial for differentiating optimal behaviour across different contexts, but how internal context such as hunger influence hippocampal circuits to define behaviour is not known. Pyramidal neurons in the ventral hippocampus, including 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. But how ghrelin influences vS has not been directly investigated. In this study, we used a combination of electrophysiology, optogenetics and 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) increased when animals approached and investigated food, and 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 postsynaptic influence of inhibition, and promoted the initiation of eating. Furthermore, this peripheral ghrelin-induced inhibition required postsynaptic expression of the ghrelin receptor GHSR1a in vS-NAc neurons, and 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.