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Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety

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Abstract

Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.

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Acknowledgements

This review was supported by the National Natural Science Foundation of China (31970951), the Six Talent Peaks Project of Jiangsu Province (YY-005), the Shanghai Rising-Star Program (21QA1407900), and “Zhong Ying Young Scholar” project of Cyrus Tang Foundation.

Author information

Author notes

  1. Hu-Jiang Shi and Shuang Wang contributed equally to this review.

Authors and Affiliations

  1. Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China

    Hu-Jiang Shi, Shuang Wang, Xin-Ping Wang, Rui-Xin Zhang & Li-Juan Zhu

  2. Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China

    Li-Juan Zhu

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  1. Hu-Jiang Shi
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  2. Shuang Wang
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  3. Xin-Ping Wang
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  4. Rui-Xin Zhang
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  5. Li-Juan Zhu
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Correspondence to Li-Juan Zhu.

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Shi, HJ., Wang, S., Wang, XP. et al. Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety. Neurosci. Bull. 39, 1009–1026 (2023). https://doi.org/10.1007/s12264-023-01020-1

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  • DOI: https://doi.org/10.1007/s12264-023-01020-1

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