Hippocampus-lateral septum circuitry mediates foraging-related spatial memory in rats

ABSTRACT Remembering the location of a food or water source is essential for survival. Here we identify a hippocampal-septal neural circuit that is necessary for spatial memory based specifically on appetitive reinforcement. Both reversible and chronic disconnection of ventral hippocampus CA1 subregion (CA1v) projections to the lateral-septum (LS) using pathway-specific dual viral approaches impaired spatial memory retention for the location of either food or water reinforcement. 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. 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 medial prefrontal cortex (mPFC) as a collateral target of LS-projecting CA1v neurons. However, functional disconnection of CA1v and mPFC did not affect appetitive spatial memory, 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 an environmental location based on appetitive (food or water) but not aversive (escape) reinforcement, thus identifying a novel neural pathway regulating foraging-related memory processes.