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. [Display omitted] •Chemogenetic activation of PL-BLA projections abolishes social preference•Chemogenetic inhibition of IL-BLA projections abolishes social preference•Optogenetic activation of PL-BLA induces social deficits and place avoidance•Reactivation of negative-valence encoding PL-BLA projections induces social deficits Huang et al. investigate a circuit involving two brain regions important for both social and emotional processing. Activation of descending projections to the basolateral amygdala from the prelimbic cortex abolishes social preference and produces behavioral avoidance. Reactivation of negative stimulus-responsive neurons in this circuit abolishes social preference.