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Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors

Neuropsychopharmacology (2024)Cite this article

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Abstract

Clinical studies have shown that the mediodorsal thalamus (MD) may play an important role in the development of depression. However, the molecular and circuit mechanisms by which the mediodorsal thalamus (MD) participates in the pathological processes of depression remain unclear. Here, we show that in male chronic social defeat stress (CSDS) mice, the calcium signaling activity of glutamatergic neurons in MD is reduced. By combining conventional neurotracer and transneuronal virus tracing techniques, we identify a synaptic circuit connecting MD and medial prefrontal cortex (mPFC) in the mouse. Brain slice electrophysiology and fiber optic recordings reveal that the reduced activity of MD glutamatergic neurons leads to an excitatory-inhibitory imbalance of pyramidal neurons in mPFC. Furthermore, activation of MD glutamatergic neurons restores the electrophysiological properties abnormal in mPFC. Optogenetic activation of the MD-mPFC circuit ameliorates anxiety and depression-like behaviors in CSDS mice. Taken together, these data support the critical role of MD-mPFC circuit on CSDS-induced depression-like behavior and provide a potential mechanistic explanation for depression.

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Fig. 1: The activity of MD glutamatergic neurons is reduced by CSDS.
Fig. 2: Chemogenetic manipulated of glutamatergic neurons in MD modulated anxiety and depression-like behavior.
Fig. 3: mPFC pyramidal neurons are activated by CSDS.
Fig. 4: CSDS impairs synaptic transmission from MD to mPFC.
Fig. 5: Active MD-mPFC circuit alleviated depression-like behaviors induced by CSDS.

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Acknowledgements

We appreciate the technical support by Dr. Bin Jiang at Zhongshan School of Medicine, Sun Yat-sen University.

Funding

This work was supported by the National Natural Science Foundation of China (81771144, 32200832), the Natural Science Foundation of Guangdong Province, China (2021A1515011134, 2022A1515012553).

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Author notes

  1. These authors contributed equally: Fang Li, Xuefeng Zheng.

Authors and Affiliations

  1. Department of Anatomy, Neuroscience Laboratory for Cognitive and Developmental Disorders, Medical College of Jinan University, Guangzhou, 510630, China

    Fang Li, Xuefeng Zheng, Hanjie Wang, Lianghui Meng, Meiying Chen, Yuqing Hui, Danlei Liu, Yifei Li, Keman Xie, Jifeng Zhang & Guoqing Guo

  2. Shenzhen-Hong Kong Institute of Brain Science, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China

    Fang Li

  3. Department of Gastroenterology, The First Affiliated Hospital of Jinan University, Guangzhou, 510630, China

    Yuqing Hui & Danlei Liu

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Contributions

GQG, JFZ and FL conceived and designed the study. FL, XFZ and HJW performed most of the experiments. LHM, MYC, LYF, XYY and YQH helped to establish the CSDS animal models and perform behavioral tests. DLL, YFL and KMX contributed to data analysis. FL and JFZ wrote the paper. GQG reviewed and edited the manuscript. All the authors have read and approved the final version of the manuscript.

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Correspondence to Jifeng Zhang or Guoqing Guo.

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Li, F., Zheng, X., Wang, H. et al. Mediodorsal thalamus projection to medial prefrontal cortical mediates social defeat stress-induced depression-like behaviors. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01829-y

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