Hippocampal Circuits for the Hunger-Dependent Control of Feeding Behaviour

Abstract Background: Feeding behavior is a complex motivated behavior that requires organisms to integrate features of the environment, such as food availability and value, and internal states, such as hunger, in deliberating over the decision to eat. The hippocampus - a brain region classically thought to support spatial cognition and episodic memory - is increasingly recognised to contribute to such decision-making processes. This function makes the hippocampus a likely candidate in supporting the higher-order decisions that underpin motivated behaviors such as feeding. However, the role of the hippocampus during free-feeding behavior has not been examined. Methods and Results: To address this question, we used in vivo calcium imaging during feeding behavior in mice to monitor the neural activity of the ventral subiculum (vS) - one of the main output structures of the ventral hippocampus. In a free-feeding task, we found that the vS encoded the investigative approach phase of feeding behavior and that activity during this period correlated with the probability of transitioning from food investigation to consumption. Calcium imaging during an operant task confirmed the specific encoding of preparatory behaviour preceding food consumption. Furthermore, the sensitivity of vS to the hunger state could be mapped to vS neurons projecting to the nucleus accumbens (vS-NAc). Ghrelin - a hormone signalling the hunger state - altered synaptic transmission specifically in vS-NAc neurons, and molecular knockdown of the ghrelin receptor was required for the hunger sensitivity of vS-NAc. Consequently, both reducing ghrelin signalling in vS-NAc neurons through molecular knockdown and artificially elevating vS-NAc activity through optogenetics were sufficient to shift the feeding strategy of animals, effectively curtailing overall food consumption. Conclusion: In summary, these results provide evidence for a hippocampal circuit that integrates hunger state signals to regulate the decision to eat.