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Remembering the location of a food source is essential for securing energy for survival. 3Here we identify a hippocampal-septal neural circuit that controls food-directed spatial memory. 4Both reversible and chronic disconnection of ventral hippocampus CA1 subregion (CA1v) 5 projections to the lateral-septum (LS) using pathway-specific dual viral approaches impaired 6 memory retention in a spatial food-seeking foraging task in rats. However, disconnection of this 7 pathway did not affect performance in an aversive escape-motivated spatial memory task that 8 used the same apparatus and visuospatial cues, suggesting that CA1v-LS signaling selectively 9 mediates spatial memory for food location vs. spatial memory in general. The selectivity of this 10 pathway in mediating foraging-related spatial memory was further supported by results showing 11 that CA1v-LS disconnection did not affect anxiety-like behavior, locomotor activity, or social 12 and olfactory-based appetitive learning. To examine whether CA1v-LS mediation of foraging-13 related spatial memory involves collateral projections of CA1v neurons, we utilized virus-based 14 neural pathway tracing analyses to identify the mPFC as a collateral target of LS-projecting 15 CA1v neurons. However, functional disconnection of the CA1v and mPFC did not affect spatial 16 memory for food location, thus further supporting the selectivity of CA1v-LS signaling for this 17 behavior. The nucleus accumbens, lateral hypothalamic area, and other brain regions associated 18 with food motivation and reward were identified as second-order targets of CA1v-LS signaling 19 using a multisynaptic anterograde tracing approach. Collective results reveal that CA1v to LS 20 communication plays a critical role in remembering the environmental location of food, thus 21 identifying a novel neural pathway regulating foraging-related memory processes. 22 23 24 25 26 27 28 29 30 31(temporal pole; HPCv), while classically associated with stress-and affect-associated memory 55 processes (7), also plays a role in visuospatial learning and memory (8-10). For example, under 56 some testing conditions selective HPCv lesions impair spatial memory performance in the Morris 57 water maze (10, 11). Moreover, place cells that are responsive to changes in the visuospatial 58 environment are present within both the HPCd and HPCv pyramidal layers, with a linear 59 increase in the scale of representation from the dorsal to the ventral pole (9). Despite a common 60 role for the HPCd and HPCv in mediating spatial memory, there is also evidence for a functional 61 distinction between the subregions (7, 12, 13). For instance, lesions of the HPCv but not the 62 HPCd alter stress responses (14) and anxiety-like behavior (15), whereas HPCd but not HPCv 63 lesions impair spatial memory in an incidental (nonreinforced) procedure (16). These two HPC 64 subregions also have distinct afferent and efferent neural connections. This disparate 65 neuroanatomical connectivity supports a framework for a functional diversity in ...