A circuit from the ventral subiculum to anterior hypothalamic nucleus GABAergic neurons essential for anxiety-like behavioral avoidance

Jing-Jing Yan, Xiao-Jing Ding, Ting He, Ai-Xiao Chen, Wen Zhang, Zi-Xian Yu, Xin-Yu Cheng, Chuan-Yao Wei, Qiao-Dan Hu, Xiao-Yao Liu, Yan-Li Zhang, Mengge He, Zhi-Yong Xie, Xi Zha, Chun Xu, Peng Cao, Haohong Li and Xiao-Hong Xu ()
Additional contact information
Jing-Jing Yan: Chinese Academy of Sciences
Xiao-Jing Ding: Chinese Academy of Sciences
Ting He: Huazhong University of Science and Technology
Ai-Xiao Chen: Chinese Academy of Sciences
Wen Zhang: Chinese Academy of Sciences
Zi-Xian Yu: Chinese Academy of Sciences
Xin-Yu Cheng: National Institute of Biological Sciences
Chuan-Yao Wei: Chinese Academy of Sciences
Qiao-Dan Hu: Chinese Academy of Sciences
Xiao-Yao Liu: Chinese Academy of Sciences
Yan-Li Zhang: Chinese Academy of Sciences
Mengge He: Huazhong University of Science and Technology
Zhi-Yong Xie: National Institute of Biological Sciences
Xi Zha: Chinese Academy of Sciences
Chun Xu: Chinese Academy of Sciences
Peng Cao: National Institute of Biological Sciences
Haohong Li: Zhejiang University School of Brain Science and Brain Medicine
Xiao-Hong Xu: Chinese Academy of Sciences

Nature Communications, 2022, vol. 13, issue 1, 1-16

Abstract: Abstract Behavioral observations suggest a connection between anxiety and predator defense, but the underlying neural mechanisms remain unclear. Here we examine the role of the anterior hypothalamic nucleus (AHN), a node in the predator defense network, in anxiety-like behaviors. By in vivo recordings in male mice, we find that activity of AHN GABAergic (AHNVgat+) neurons shows individually stable increases when animals approach unfamiliar objects in an open field (OF) or when they explore the open-arm of an elevated plus-maze (EPM). Moreover, object-evoked AHN activity overlap with predator cue responses and correlate with the object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons reduces object and open-arm avoidance. Furthermore, retrograde viral tracing identifies the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors in anxiogenic situations. Thus, convergent activation of AHNVgat+ neurons serves as a shared mechanism between anxiety and predator defense to promote behavioral avoidance.

Date: 2022
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DOI: 10.1038/s41467-022-35211-7

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