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

Abstract

Associative learning guides feeding behavior in mammals in part by using cues that link location in 2 space to food availability. However, the elements of the top-down circuitry encoding the memory of the 3 location of food is largely unknown, as are the high-order processes that control satiety. Here we report 4 that hippocampal dopamine 2 receptor (D2R) neurons are specifically activated by food and that 5 modulation of their activity reduce food intake in mice. We also found that activation of these neurons 6 interferes with the valence of food and the acquisition of a spatial memory linking food to a location via 7 projections from the hippocampus to the lateral septum. Finally, we showed that inputs from lateral 8 entorhinal cortex (LEC) to the hippocampus can also drive satiety via activation of D2R cells. These 9 data describe a previously unidentified function for hippocampal D2R cells to regulate feeding behavior 10 and identifies a LEC->Hippocampus->Septal high-order circuit that encodes the memory of food 11 location.