Dorsal CA1 projections to nucleus accumbens and lateral septum differentially regulate social and locomotor behavior.

Beyond its established role in spatial and episodic memory, the dorsal hippocampus also shapes motivated behavior by routing contextual information to downstream targets. Dorsal CA1 (dCA1) projects to the nucleus accumbens (NAc) and lateral septum (LS); here, we show that these pathways regulate distinct behaviors. We mapped and selectively manipulated these circuits in mice using projection-specific viral tracing, intersectional labeling, and terminal optogenetics. Activating dCA1-to-NAc terminals selectively increased social interaction without altering locomotion or novel-object exploration, consistent with a role in social motivation rather than generalized exploration. In contrast, the dCA1-to-LS pathway bidirectionally regulated locomotion, with activation increasing movement and inhibition decreasing locomotion without specifically influencing social behavior. Intersectional labeling also identified a small population of dCA1 neurons that projects to both targets. Together, these findings suggest that distinct dCA1 output pathways can differentially regulate social interaction and locomotor state, providing a circuit-level view of how hippocampal contextual signals are routed to subcortical regions.