Divergent BLA engram circuits orchestrate social preference dynamics in bystander male mice with self-experienced stress

X Xue-Ke Yang (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) Y Yu-Long Shi (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) M Ming Li T Tong-Xia Li (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) J Jian Yang J Jie Lei (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) C Chi Cui (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) X Xiang Peng (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) H Hong-Chu Zha (Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology) G Gan-Gan Luo (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) Y Yi-Bo Yao (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) S Si-Tong Chen (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) J Jun-Song Du (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) H Hui-Juan Wang (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) S Shi-Qi Xu (Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology) P Pei Zhang (Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology) B Bo Tian (Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology)

Abstract

Personal experiences are encoded and stored in memory engram cells and are crucial for social preference dynamics in future social contexts, yet the neural circuit mechanisms involved are still poorly understood. Here, we develop a mouse model that combines self-experienced single social defeat stress with vicarious social defeat stress, demonstrating a social preference with defeat stress-experienced cagemate and social avoidance toward an aggressor. Basolateral amygdala engram cells (BLA EC ) exhibit significant activation, and chemogenetic manipulations confirm their sufficiency and necessity for both social preference and social avoidance behaviors. Virus-based cell-type-specific brain mapping suggests BLA EC project to anterior cingulate cortex (ACC) and these projections are also responsible for modulating social preference dynamics. Distinct projections from BLA-ACC circuit, including ventral/dorsal hippocampus and zona incerta, exert the diverse effects on these behaviors in male mice. Our findings reveal regulation of social preference dynamics by divergent circuits originating from BLA EC , which may contribute to the neurobiological mechanism of social psychopathologies.

Article Details

Volume / Issue Vol. 123, Issue 11
Published March 17, 2026
ISSN 0027-8424
Publisher National Academy of Sciences

Authors (17)

X

Xue-Ke Yang

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

Y

Yu-Long Shi

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

M

Ming Li

T

Tong-Xia Li

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

J

Jian Yang

J

Jie Lei

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

C

Chi Cui

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

X

Xiang Peng

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

H

Hong-Chu Zha

Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology

G

Gan-Gan Luo

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

Y

Yi-Bo Yao

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

S

Si-Tong Chen

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

J

Jun-Song Du

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

H

Hui-Juan Wang

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

S

Shi-Qi Xu

Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology

P

Pei Zhang

Department of Neurobiology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology

B

Bo Tian

Hubei Provincial Clinical Research Center for Alzheimer’s Disease, Brain Science and Advanced Technology Institute, Tianyou Hospital, School of Medicine, Wuhan University of Science and Technology