Hippocampus-lateral septum circuitry mediates memory for food location in rats

Remembering the location of a food source is essential for securing energy for survival. Here we identify a hippocampal-septal neural circuit that controls food-directed spatial memory. Both reversible and chronic disconnection of ventral hippocampus CA1 subregion (CA1v) projections to the lateral-septum (LS) using pathway-specific dual viral approaches impaired memory retention in a spatial food-seeking foraging task in rats. However, disconnection of this pathway did not affect performance in an aversive escape-motivated spatial memory task that used the same apparatus and visuospatial cues, suggesting that CA1v-LS signaling selectively mediates spatial memory for food location vs. spatial memory in general. The selectivity of this pathway in mediating foraging-related spatial memory was further supported by results showing that CA1v-LS disconnection did not affect anxiety-like behavior, locomotor activity, or social and olfactory-based appetitive learning. To examine whether CA1v-LS mediation of foraging-related spatial memory involves collateral projections of CA1v neurons, we utilized virus-based neural pathway tracing analyses to identify the mPFC as a collateral target of LS-projecting CA1v neurons. However, functional disconnection of the CA1v and mPFC did not affect spatial memory for food location, thus further supporting the selectivity of CA1v-LS signaling for this behavior. The nucleus accumbens, lateral hypothalamic area, and other brain regions associated with food motivation and reward were identified as second-order targets of CA1v-LS signaling using a multisynaptic anterograde tracing approach. Collective results reveal that CA1v to LS communication plays a critical role in remembering the environmental location of food, thus identifying a novel neural pathway regulating foraging-related memory processes.