PT - JOURNAL ARTICLE AU - Julieta E. Lischinsky AU - Luping Yin AU - Chenxi Shi AU - Nandkishore Prakash AU - Jared Burke AU - Govind Shekaran AU - Maria Grba AU - Joshua G. Corbin AU - Dayu Lin TI - Hardwired to attack: Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors AID - 10.1101/2023.03.16.532692 DP - 2023 Jan 01 TA - bioRxiv PG - 2023.03.16.532692 4099 - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532692.short 4100 - http://biorxiv.org/content/early/2023/03/17/2023.03.16.532692.full AB - Social behaviors are innate and supported by dedicated neural circuits, but it remains unclear whether these circuits are developmentally hardwired or established through social experience. Here, we revealed distinct response patterns and functions in social behavior of medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages. MeA cells in male mice that express the transcription factor Foxp2 (MeAFoxp2) are specialized for processing male conspecific cues even before puberty and are essential for adult inter-male aggression. In contrast, MeA cells derived from the Dbx1-lineage (MeADbx1) respond broadly to social cues and are non-essential for male aggression. Furthermore, MeAFoxp2 and MeADbx1 cells show differential anatomical and functional connectivity. Altogether, our results support a developmentally hardwired aggression circuit at the level of the MeA and we propose a lineage-based circuit organization by which a cell’s embryonic transcription factor profile determines its social information representation and behavior relevance during adulthood.HighlightsMeAFoxp2 cells in male mice show highly specific responses to male conspecific cues and during attack while MeADbx1 cells are broadly tuned to social cues.The male-specific response of MeAFoxp2 cells is present in naïve adult males and adult social experience refines the response by increasing its trial-to-trial reliability and temporal precision.MeAFoxp2 cells show biased response to males even before puberty.Activation of MeAFoxp2, but not MeADbx1, cells promote inter-male aggression in naïve male mice.Inactivation of MeAFoxp2, but not MeADbx1, cells suppresses inter-male aggression.MeAFoxp2 and MeADbx1 cells show differential connectivity at both the input and output levels.Competing Interest StatementThe authors have declared no competing interest.