The role of nutrient‐responsive hippocampal neurons in feeding

Abstract

Feeding behavior is controlled by hippocampal‐dependent learning and memory that influence decisions about where, when and what to eat. However, the neuronal subtypes and stimuli that recruit these neurons remain poorly understood.Here we leverage the unique strength of the recently‐developed Targeted Recombination in Activated Populations (TRAP2) mouse model, which provides cell type‐unbiased genetic access to neuronal populations based on their activation by defined and time‐constrained stimuli. Surprisingly, after comparing neuronal activity to separate post‐ingestive stimuli within the same animal, we identified distinct hippocampal subpopulations that respond to either fat or sugar. We validated a protocol for selective ablation of the sugar‐activated hippocampal neurons using viral mediated caspase in the TRAP2 mice. Using an automated feeding system, we found that these sugar‐ablated mice significantly reduced their chow and high‐fat diet intake compared to control littermates, and exhibited impaired food location memory in a sugar‐driven food cup task. No group differences were observed in the ability to learn a flavor‐nutrient conditioning paradigm.Overall, these results demonstrate that the hippocampus is attuned to specific macronutrients rather than the feeding state, allowing highly‐refined appetitive learning and memory in response to context‐specific feeding cues.