Social isolation impairs the prefrontal-nucleus accumbens circuit subserving social recognition in mice

Although medial prefrontal cortex (mPFC) is known to play important roles in social behaviors, how early social experiences affect the mPFC and its subcortical circuit remains unclear. We report that mice singly housed (SH) for 8 weeks after weaning show a social recognition deficit, even after 4 weeks of resocialization. In SH mice, prefrontal infralimbic (IL) neurons projecting to the shell region of nucleus accumbens (NAcSh) show decreased excitability compared with group-housed (GH) mice. NAcSh-projecting IL neurons are activated when GH mice encounter a familiar conspecific, which is not observed in SH mice. Chemogenetic inhibition of NAcSh-projecting IL neurons in normal mice impairs social recognition without affecting social preference, whereas activation of these neurons reverses social recognition deficit in SH mice. Our findings demonstrate that early social experience critically affects mPFC IL-NAcSh projection, the activation of which is required for social recognition by encoding information for social familiarity. [Display omitted] •Social isolation decreases the excitability of NAcSh-projecting IL neurons•NAcSh-projecting IL neurons are activated by familiar conspecifics•Inhibition of NAcSh-projecting IL neurons impairs social recognition•Activating NAcSh-projecting IL neurons rescues social recognition deficit in SH mice Park et al. identifies a brain circuit critical for social recognition. Inhibition of the neural projection from infralimbic cortex to nucleus accumbens shell impairs social recognition without affecting social preference, which reconciles the behavioral phenotype shown in socially isolated mice. Reactivation of the same neurons rescues its social recognition deficit.