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mGluR5 in hippocampal CA1 pyramidal neurons mediates stress-induced anxiety-like behavior

Neuropsychopharmacology volume 48, pages 1164–1174 (2023)Cite this article

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Abstract

Pharmacological manipulation of mGluR5 has showed that mGluR5 is implicated in the pathophysiology of anxiety and mGluR5 has been proposed as a potential drug target for anxiety disorders. Nevertheless, the mechanism underlying the mGluR5 involvement in stress-induced anxiety-like behavior remains largely unknown. Here, we found that chronic restraint stress induced anxiety-like behavior and decreased the expression of mGluR5 in hippocampal CA1. Specific knockdown of mGluR5 in hippocampal CA1 pyramidal neurons produced anxiety-like behavior. Furthermore, both chronic restraint stress and mGluR5 knockdown impaired inhibitory synaptic inputs in hippocampal CA1 pyramidal neurons. Notably, positive allosteric modulator of mGluR5 rescued stress-induced anxiety-like behavior and restored the inhibitory synaptic inputs. These findings point to an essential role for mGluR5 in hippocampal CA1 pyramidal neurons in mediating stress-induced anxiety-like behavior.

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Fig. 1: Chronic restraint stress leaded to anxiety-like behaviors and impaired the synaptic inputs in hippocampal CA1 pyramidal neurons.
Fig. 2: Chronic restraint stress decreases mGluR5 expression in hippocampal CA1 and mGluR5 knockdown produced anxiety-like behaviors.
Fig. 3: Knockdown of mGluR5 in hippocampal CA1 pyramidal neurons impairs inhibitory synaptic inputs.
Fig. 4: The CDPPB restored stress-impaired inhibitory synaptic inputs.
Fig. 5: The CDPPB restored stress-induced anxiety-like behavior.

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Funding

Funding

This work was supported by grants from the STI2030-Major Projects (2021ZD0202704), the National Natural Science Foundation of China (82090032, 31830033, 32200950), the Key-Area Research and Development Program of Guangdong Province (2018B030334001, 2018B030340001), the Science and Technology Program of Guangzhou (202007030013), Basic and Applied Basic Research Foundation of Guangdong Province, China (2022A1515011106).

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  1. These authors contributed equally: Xin Li, Zhuo-Jun Du.

Authors and Affiliations

  1. State Key Laboratory of Organ Failure Research, Institute of Brain Diseases, Nanfang Hospital, Southern Medical University; Key Laboratory of Mental Health of the Ministry of Education, Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangdong Province Key Laboratory of Psychiatric Disorders, Department of Neurobiology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, China

    Xin Li, Zhuo-Jun Du, Jun-Nan Xu, Zhi-Man Liang, Song Lin, Hao Chen, Shu-Ji Li, Xiao-Wen Li, Jian-Ming Yang & Tian-Ming Gao

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Contributions

T-MG proposed the concept and designed the experiments. XL, Z-JD. J-NX, Z-ML, SL, HC, and S-JL performed the experiments. XL, Z-JD, and X-WL analyzed the results. XL and Z-JD interpreted the results. T-MG, J-MY, and XL wrote and edited the manuscript.

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Correspondence to Tian-Ming Gao.

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Li, X., Du, ZJ., Xu, JN. et al. mGluR5 in hippocampal CA1 pyramidal neurons mediates stress-induced anxiety-like behavior. Neuropsychopharmacol. 48, 1164–1174 (2023). https://doi.org/10.1038/s41386-023-01548-w

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