Wee, Ryan Wei Shien; (2020) Ventral hippocampal circuits for the state-dependent control of feeding behaviour. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The hippocampus is classically thought to support spatial cognition and episodic memory, but increasing evidence indicates that the hippocampus is also important for non-spatial, motivated behaviour. Hunger is an internal motivational state that not only directly invigorates behaviour towards food, but can also act as a contextual signal to support adaptive behaviour. Lesions to the hippocampus impair the internal sensing of hunger as a context, and hippocampal neurons express receptors for hunger-related hormones. However, it remains unclear whether the hippocampus is involved in sensing hunger and, if so, how hunger state sensing modulates hippocampal activity at the circuit and cellular levels to alter behaviour. Using in vivo Ca2+ imaging during naturalistic and operant-based feeding behaviour, pharmacogenetics, anatomical tracing, whole-cell electrophysiology and molecular knockdown approaches, in this PhD I probed the functional role of the ventral subiculum (vS) circuitry in hunger state sensing during feeding behaviour. The results obtained implicates the vS in encoding the anticipation of food consumption. This encoding is both specific to vS projections to the nucleus accumbens (vSNAc) and dependent on the hunger state; hunger inhibits the activity of vSNAc neurons, and this inhibition relies on ghrelin receptor signalling in vSNAc neurons. Furthermore, altering the activity of vSNAc neurons shifts the probability of transitioning from food exploration to consumption. Finally, there is a distinct input connectivity to individual vS projections, providing a potential neural basis for the heterogeneous functions of projection-specific vS neurons. Overall, this PhD advances the understanding of hippocampal function to encompass a nonspatial domain - the sensing of the hunger state – as well as clarify the cellular- and circuit-level mechanisms involved in hunger state sensing. This work presents evidence for a neural mechanism by which hunger can act as a contextual signal and alter behaviour through defined output projections from the ventral hippocampus.

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