Dorsal–Caudal and Ventral Hippocampi Target Different Cell Populations in the Medial Frontal Cortex in Rodents

Direct projections from the ventral hippocampus (vHPC) to the medial frontal cortex (MFC) play crucial roles in memory and emotional regulation. Using anterograde transsynaptic tracing and ex vivo electrophysiology in male mice, we document a previously unexplored pathway that parallels the established vHPC-MFC connectivity. This pathway connects the dorsal-caudal hippocampus (dcHPC) to specific subregions of the ventral MFC (vMFC), in particular the dorsal peduncular cortex. Notably, this pathway exerts a strong inhibitory influence on vMFC by targeting a substantial proportion of inhibitory neurons. Retrograde transsynaptic tracing in male rats indicated that vMFC subregions project disynaptically back to vHPC. These results, altogether, suggest the existence of a remarkable functional circuit connecting distinct functional areas: the cognition-related dcHPC with the emotion-related vMFC and vHPC. These findings further provide valuable insights in the cognitive and emotional abnormalities associated with the HPC-MFC connectivity in neurological and psychiatric disorders.