Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Seungmoon Jung
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Jieun Kim
Department of Bio-Health Technology, College of Biomedicine Science, Kangwon National University, Chuncheon 24341, South Korea; Multidimensional Genomics Research Center, Kangwon National University, Chuncheon 24341, South Korea
Dahm So
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea; Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea
Arie Kim
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Sowon Kim
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Sungjoon Choi
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Eunsu Yoo
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Jee Yeon Kim
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Yoon Cheol Jang
Research Solution Center, Institute for Basic Science, Daejeon 34126, South Korea
Hyoin Lee
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Jeongyeon Kim
Emotion, Cognition and Behavior Research Group, Korea Brain Research Institute, Daegu 41062, South Korea
Hee-Sup Shin
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea
Sehyun Chae
Multidimensional Genomics Research Center, Kangwon National University, Chuncheon 24341, South Korea; Division of Chemical Engineering and Bioengineering, College of Art, Culture and Engineering, Kangwon National University, Chuncheon 24341, South Korea; Corresponding author
Sehoon Keum
Center for Cognition and Sociality, Institute for Basic Science, Daejeon 34126, South Korea; Corresponding author
Summary: Empathy, crucial for social interaction, is impaired across various neuropsychiatric conditions. However, the genetic and neural underpinnings of empathy variability remain elusive. By combining forward genetic mapping with transcriptome analysis, we discover that aryl hydrocarbon receptor nuclear translocator 2 (ARNT2) is a key driver modulating observational fear, a basic form of affective empathy. Disrupted ARNT2 expression in the anterior cingulate cortex (ACC) reduces affect sharing in mice. Specifically, selective ARNT2 ablation in somatostatin (SST)-expressing interneurons leads to decreased pyramidal cell excitability, increased spontaneous firing, aberrant Ca2+ dynamics, and disrupted theta oscillations in the ACC, resulting in reduced vicarious freezing. We further demonstrate that ARNT2-expressing SST interneurons govern affective state discrimination, uncovering a potential mechanism by which ARNT2 polymorphisms associate with emotion recognition in humans. Our findings advance our understanding of the molecular mechanism controlling empathic capacity and highlight the neural substrates underlying social affective dysfunctions in psychiatric disorders.
