2. Academic Validation
  3. Medial prefrontal cortex-periaqueductal gray circuit overcomes anxiety-like behavior in male mice following adversity

Medial prefrontal cortex-periaqueductal gray circuit overcomes anxiety-like behavior in male mice following adversity

  • J Affect Disord. 2025 Mar 1:372:149-159. doi: 10.1016/j.jad.2024.12.017.
Jiahui Qian 1,  Wei Wu 1,  Lianli Qiu 2,  Xiang Liu 1,  Yifeng Luo 3,  Feng Chen 4,  Wesley Surento 5,  Yueqin Liu 6,  Guangming Lu 7,  Rongfeng Qi 8
Affiliations

Affiliations

  • 1 Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China.
  • 2 Department of Radiology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China.
  • 3 Department of Radiology, The Affiliated Yixing Hospital of Jiangsu University, Wuxi, China.
  • 4 Department of Radiology, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), No. 19, Xiuhua Street, Xiuying District, Haikou 570311, Hainan, China.
  • 5 Department of Biomedical Informatics and Medical Education, University of Washington, Seattle, WA, USA.
  • 6 Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: yql918@mail.ustc.edu.cn.
  • 7 Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China. Electronic address: cjr.luguangming@vip.163.com.
  • 8 Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China; Department of Radiology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, No. 321 Zhongshan Road, Nanjing 210008, China. Electronic address: qirongfeng@163.com.
PMID: 39638057 DOI: 10.1016/j.jad.2024.12.017
Abstract

Background: Inescapable stress leads to various long-lasting physical and mental dysfunctions. Acute stress exposure is linked to a high risk of psychological disorders, such as anxiety disorders. The medial prefrontal cortex (mPFC) and periaqueductal gray (PAG) are anatomical regions associated with social information processing and emotional valence. However, it is unclear whether mPFC projections to the PAG are involved in anxiety behavior.

Methods: In this study, an anxiety model by an inescapable foot shock was established. And used immunofluorescence, FosTRAP strategy, specific chemogenetics, optogenetics and behavior test to reveal that the stressful event increased the anxiety behavior of mice after exposure to foot shock and activation of mPFC-PAG circuitry can improve anxiety-like behavior and the locomotor behavior of mice.

Results: Notably, FosTRAP results indicated that c-Fos expression in the PAG and mPFC is increased during foot shock, but inhibiting these brain regions did not significantly alleviate anxiety behavior. Additionally, chemogenetic activation of mPFC projections to the PAG improved anxiety-like behavior and locomotor activity in mice only during stress. Optogenetic activation of the mPFC-PAG circuitry increased the total distance traveled in the open field test and slightly increased the number of entries into the center area, while optogenetic inhibition slightly increased anxiety-like behavior in control mice.

Limitation: The limitation of this study is that only the changes and regulations of mPFC-PAG of anxiety male Animals were studied.

Conclusions: Overall, our findings suggest that the valence-encoding mPFC-PAG circuit modulates anxiety, and that these projections may be potential targets for treatment of anxiety disorders.

Keywords

Anxiety-like behavior; Optogenetics; PAG; mPFC.

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