A circuit from dorsal hippocampal CA3 to parvafox nucleus mediates chronic social defeat stress–induced deficits in preference for social novelty

The preference for social novelty is crucial to the social life of humans and rodents. However, the neural mechanisms underlying social novelty preference are poorly understood. Here, we found that chronic social defeat stress (CSDS) reduced the preference for social novelty in mice by impairing the response of CaMKIIα(+) neurons in the CA3 region of dorsal hippocampus (dCA3) during approach to an unfamiliar mouse. The deficits of social novelty preference in CSDS-treated mice were reversed by activating the output from dCA3 to the GABAergic neurons in the lateral septum (LS). The activation of GABAergic projection from LS recruited a circuit that inhibited the Foxb1(+) neurons in the parvafox nucleus (PFN), which drove social avoidance by projecting to the lateral periaqueductal gray (lPAG). These results suggest that a previously unidentified circuit of dCA3(CaMKIIα+)→LS(GABA+)→PFN(Foxb1+)→lPAG mediates the deficits of social novelty preference induced by CSDS.