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Reply to ‘Fear, anxiety and the functional architecture of the human central extended amygdala’

Nature Reviews Neuroscience volume 25, pages 589–590 (2024) Cite this article

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We thank Shackman et al. for their correspondence on our Review article (Tseng, Y. T., Schaefke, B., Wei, P. & Wang, L. Defensive responses: behaviour, the brain and the body. Nat. Rev. Neurosci. 24, 655–671; 2023)1, which raises interesting issues about the functional relationship between the human central nucleus of the amygdala (CeA) and the bed nucleus of the stria terminalis (BNST) (Shackman, A. J., Grogans, S. E. & Fox, A. S. Fear, anxiety and the functional architecture of the human central extended amygdala. Nat. Rev. Neurosci. https://doi.org/10.1038/s41583-024-00832-y (2024))2. Here, we briefly address claim 2 (“the CeA alone triggers responses to more certain-and-immediate dangers”2) drawn by Shackman and colleagues from our Review and discuss the proposed role of the BNST in responses to higher-imminence threat, which we did not present in our piece.

In our Review, we focused on the established neurocircuits activated within the predatory imminence continuum, as confirmed in rodent studies, and their interplay with peripheral systems. Causal studies in mice have clearly shown that the CeA is required for responses to high-imminence threat in the circa-strike phase under ethologically relevant conditions1,3. However, corresponding research on the BNST is limited, with no study clearly establishing a causal role of the BNST in regulating the response to high-imminence predator (or equivalent) threat. Shackman et al. cite a study which shows that optogenetic stimulation of serotonin-responsive neurons in the BNST during fear acquisition strengthens responses to Pavlovian threat cues during fear recall4. This is an exciting finding; however, it does not show BNST activation under ethologically relevant conditions in direct response to a high-imminence threat. Our Review consequently focused predominantly on causal studies, which have well characterized the BNST’s role in regulating rodent responses to lower-imminence threat.

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References

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Acknowledgements

The authors acknowledge assistance from M.-H. Han and B. Li. This work was supported by grants from the National Natural Science Foundation of China (32230042 to L.W.; 32200826 to Y.-T.T.), the Shenzhen Science and Technology Program (JCYJ20220530154412028 to Y.-T.T.; KCXFZ20211020163549011 to B.S.) and the Financial Support for Outstanding Talents Training Fund in Shenzhen (to L.W.).

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Authors and Affiliations

  1. Key Laboratory of Brain Cognition and Brain-inspired Intelligence Technology, Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Liping Wang, Yu-Ting Tseng, Bernhard Schaefke & Pengfei Wei

  2. Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, the Brain Cognition and Brain Disease Institute, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, China

    Liping Wang, Yu-Ting Tseng, Bernhard Schaefke & Pengfei Wei

  3. State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China

    Sheng He

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  1. Liping Wang
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Correspondence to Liping Wang.

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Wang, L., Tseng, YT., Schaefke, B. et al. Reply to ‘Fear, anxiety and the functional architecture of the human central extended amygdala’. Nat. Rev. Neurosci. 25, 589–590 (2024). https://doi.org/10.1038/s41583-024-00834-w

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