ARNT2 controls prefrontal somatostatin interneurons mediating affective empathy

被引:3
|
作者
Choi, Jiye [1 ]
Jung, Seungmoon [1 ]
Kim, Jieun [2 ,3 ]
So, Dahm [1 ,4 ]
Kim, Arie [1 ]
Kim, Sowon [1 ]
Choi, Sungjoon [1 ]
Yoo, Eunsu [1 ]
Kim, Jee Yeon [1 ]
Jang, Yoon Cheol [5 ]
Lee, Hyoin [1 ]
Kim, Jeongyeon [6 ]
Shin, Hee-Sup [1 ]
Chae, Sehyun [3 ,7 ]
Keum, Sehoon [1 ]
机构
[1] Inst for Basic Sci Korea, Ctr Cognit & Social, Daejeon 305338, South Korea
[2] Kangwon Natl Univ, Coll Biomed Sci, Dept Biohlth Technol, Chunchon 24341, South Korea
[3] Kangwon Natl Univ, Multidimens Genom Res Ctr, Chunchon 24341, South Korea
[4] Korea Adv Inst Sci & Technol, Dept Bio & Brain Engn, Daejeon 34141, South Korea
[5] Inst for Basic Sci Korea, Res Solut Ctr, Daejeon 34126, South Korea
[6] Korea Brain Res Inst, Emot Cognit & Behav Res Grp, Daegu 41062, South Korea
[7] Kangwon Natl Univ, Coll Art Culture & Engn, Div Chem Engn & Bioengn, Chunchon 24341, South Korea
来源
CELL REPORTS | 2024年 / 43卷 / 09期
基金
新加坡国家研究基金会;
关键词
INBRED STRAINS; NEURAL BASIS; NEURONS; GENES; MICE; DISCRIMINATION; ACTIVATION; MECHANISMS; STRATEGIES; ABILITIES;
D O I
10.1016/j.celrep.2024.114659
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页数:24
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