Encoding of an engram for food location by satiety-promoting Drd2 hippocampal neurons

SUMMARY Associative learning guides feeding behavior in mammals in part by using cues that link location in space to food availability. However, the elements of the top-down circuitry encoding the memory of the location of food is largely unknown, as are the high-order processes that control satiety. Here we report that hippocampal dopamine 2 receptor (D2R) neurons are specifically activated by food and that modulation of their activity reduce food intake in mice. We also found that activation of these neurons interferes with the valence of food and the acquisition of a spatial memory linking food to a location via projections from the hippocampus to the lateral septum. Finally, we showed that inputs from lateral entorhinal cortex (LEC) to the hippocampus can also drive satiety via activation of D2R cells. These data describe a previously unidentified function for hippocampal D2R cells to regulate feeding behavior and identifies a LEC->Hippocampus->Septal high-order circuit that encodes the memory of food location.