Dorsal-caudal and ventral hippocampus 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, in particular the dorsal peduncular cortex. Notably, this pathway exerts a strong inhibitory influence on ventral MFC by targeting a substantial proportion of inhibitory neurons. Retrograde transsynaptic tracing in male rats indicated that ventral MFC 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 ventral MFC 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.Significance of statement We re-examined the organization of the circuits connecting the hippocampus (HPC) to the medial frontal cortex (MFC) in rodents. We found that dorsal-caudal HPC innervates robustly neurons in ventral subregions of MFC, particularly the dorsal peduncular cortex (DP), including a significant population of inhibitory neurons. Our results show that DP, a subregion critical for emotional and autonomic control, can be modulated by the direct projection from the more cognition-related dorsal-caudal HPC.