Transcriptionally defined amygdala subpopulations play distinct roles in innate social behaviors

• Published in: Nature neuroscience Vol. 26; no. 12; pp. 2131 - 2146
• Main Authors: Lischinsky, Julieta E., Yin, Luping, Shi, Chenxi, Prakash, Nandkishore, Burke, Jared, Shekaran, Govind, Grba, Maria, Corbin, Joshua G., Lin, Dayu
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2023; Nature Publishing Group
• Subjects: 13/51; 14; 14/19; 14/63; 631/378/3917; 631/378/3919; 631/378/3920; 631/378/87; 64/60; 9/74; Aggression; Amygdala; Amygdala - physiology; Animal Genetics and Genomics; Animals; Behavior; Behavioral Sciences; Biological Techniques; Biomedical and Life Sciences; Biomedicine; Circuits; Corticomedial Nuclear Complex; Cues; Dbx1 protein; Ejaculation; Embryos; Foxp2 protein; Homeodomain Proteins - metabolism; Information processing; Male; Males; Mice; Neural networks; Neurobiology; Neurons - physiology; Neurosciences; Social Behavior; Social interactions; Subpopulations; Transcription factors; Transcription Factors - genetics
• ISSN: 1097-6256; 1546-1726; 1546-1726
• DOI: 10.1038/s41593-023-01475-5

Social behaviors are innate and supported by dedicated neural circuits, but the molecular identities of these circuits and how they are established developmentally and shaped by experience remain unclear. Here we show that medial amygdala (MeA) cells originating from two embryonically parcellated developmental lineages have distinct response patterns and functions in social behavior in male mice. MeA cells expressing the transcription factor Foxp2 (MeA Foxp2 ) are specialized for processing male conspecific cues and are essential for adult inter-male aggression. By contrast, MeA cells derived from the Dbx1 lineage (MeA Dbx1 ) respond broadly to social cues, respond strongly during ejaculation and are not essential for male aggression. Furthermore, MeA Foxp2 and MeA Dbx1 cells show differential anatomical and functional connectivity. Altogether, our results suggest a developmentally hardwired aggression circuit at the MeA level and a lineage-based circuit organization by which a cell’s embryonic transcription factor profile determines its social information representation and behavioral relevance during adulthood. The authors describe the connectivity, response profile and behavioral roles of two transcriptionally defined amygdala populations from separate embryonic lineages and show how responses of one population change with social experience.