Social Behavior Is Modulated by Valence-Encoding MPFC-Amygdala Sub-circuitry

The prefrontal cortex and amygdala are anatomical substrates linked to both social information and emotional valence processing, but it is not known whether sub-circuits in the medial prefrontal cortex (mPFC) that project to the basolateral amygdala (BLA) are recruited and functionally contribute to social approach-avoidance behavior. Using retrograde labeling of mPFC projections to the BLA, we find that BLA-projecting neurons in the infralimbic cortex (IL) are preferentially activated in response to a social cue as compared with BLA-projecting neurons in the prelimbic cortex (PL). Chemogenetic interrogation of these sub-circuits shows that activation of PL-BLA or inhibition of IL-BLA circuits impairs social behavior. Sustained closed-loop optogenetic activation of PL-BLA circuitry induces social impairment, corresponding to a negative emotional state as revealed by real-time place preference behavioral avoidance. Reactivation of foot shock-responsive PL-BLA circuitry impairs social behavior. Altogether, these data suggest a circuit-level mechanism by which valence-encoding mPFC-BLA sub-circuits shape social approach-avoidance behavior.