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A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance

Jing-Jing Yan, Ai-Xiao Chen, Wen Zhang, Ting He, Xiao-Jing Ding, Zi-Xian Yu, Yan-Li Zhang, Mengge He, Haohong Li, Xiao-Hong Xu
doi: https://doi.org/10.1101/2022.01.17.476545
Jing-Jing Yan
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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Ai-Xiao Chen
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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Wen Zhang
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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Ting He
5Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
6MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
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Xiao-Jing Ding
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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Zi-Xian Yu
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
3University of Chinese Academy of Sciences, Beijing 100049, China
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Yan-Li Zhang
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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Mengge He
5Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
6MoE Key Laboratory for Biomedical Photonics, Collaborative Innovation Center for Biomedical Engineering, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China
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Haohong Li
4The MOE Frontier Research Center of Brain & Brain machine Integration, Zhejiang University School of Brain Science and Brain Medicine, Hangzhou Zhejiang 310058, China
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Xiao-Hong Xu
1Institute of Neuroscience, State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai 200031, China
2Shanghai Center for Brain Science and Brain-Inspired Intelligence Technology, Shanghai 200031, China
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  • For correspondence: xiaohong.xu@ion.ac.cn
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Abstract

Anxiety over perceived threats triggers avoidance behavior, but the underlying neural circuit mechanism remains poorly understood. Taking hints from the deep connection between anxiety and predator defense, we examined the role of the anterior hypothalamic nucleus (AHN), a critical node in the predator defense network, in anxiety-related behaviors. By recording Ca2+ transients in behaving mice, we found that activity of AHN GABAergic (AHNVgat+) neurons showed individually stable increases when animals approached unfamiliar objects in an open field (OF) or explored the open arm of an elevated plus-maze (EPM). Moreover, AHNVgat+ neuron activity foreshadowed behavioral retreats and correlated with object and open-arm avoidance. Crucially, exploration-triggered optogenetic inhibition of AHNVgat+ neurons dramatically reduced avoidance behaviors. Furthermore, retrograde viral tracing identified the ventral subiculum (vSub) of the hippocampal formation as a significant input to AHNVgat+ neurons in driving avoidance behaviors. Thus, the activity of the hippocampal-hypothalamic pathway promotes idiosyncratic anxiety-related behavioral avoidance.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • ↵8 Lead contact

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Posted January 18, 2022.
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A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance
Jing-Jing Yan, Ai-Xiao Chen, Wen Zhang, Ting He, Xiao-Jing Ding, Zi-Xian Yu, Yan-Li Zhang, Mengge He, Haohong Li, Xiao-Hong Xu
bioRxiv 2022.01.17.476545; doi: https://doi.org/10.1101/2022.01.17.476545
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A hippocampal-hypothalamic circuit essential for anxiety-related behavioral avoidance
Jing-Jing Yan, Ai-Xiao Chen, Wen Zhang, Ting He, Xiao-Jing Ding, Zi-Xian Yu, Yan-Li Zhang, Mengge He, Haohong Li, Xiao-Hong Xu
bioRxiv 2022.01.17.476545; doi: https://doi.org/10.1101/2022.01.17.476545

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