Qian Jiahui, Wu Wei, Qiu Lianli, Liu Xiang, Luo Yifeng, Chen Feng, Surento Wesley, Liu Yueqin, Lu Guangming, Qi Rongfeng
Department of Radiology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu 210002, China.
Department of Radiology, Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu 210002, China.
J Affect Disord. 2025 Mar 1;372:149-159. doi: 10.1016/j.jad.2024.12.017. Epub 2024 Dec 3.
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.
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.
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.
The limitation of this study is that only the changes and regulations of mPFC-PAG of anxiety male animals were studied.
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.
不可逃避的应激会导致各种长期的身心功能障碍。急性应激暴露与心理障碍的高风险相关，如焦虑症。内侧前额叶皮质（mPFC）和导水管周围灰质（PAG）是与社会信息处理和情绪效价相关的解剖区域。然而，尚不清楚mPFC向PAG的投射是否参与焦虑行为。
在本研究中，通过不可逃避的足部电击建立了焦虑模型。并使用免疫荧光、FosTRAP策略、特定化学遗传学、光遗传学和行为测试来揭示应激事件增加了小鼠在遭受足部电击后的焦虑行为，并且mPFC-PAG神经回路的激活可以改善小鼠的焦虑样行为和运动行为。
值得注意的是，FosTRAP结果表明，在足部电击期间，PAG和mPFC中的c-Fos表达增加，但抑制这些脑区并未显著减轻焦虑行为。此外，mPFC向PAG的投射的化学遗传学激活仅在应激期间改善了小鼠的焦虑样行为和运动活动。mPFC-PAG神经回路的光遗传学激活增加了旷场试验中的总行进距离，并略微增加了进入中心区域的次数，而光遗传学抑制则略微增加了对照小鼠的焦虑样行为。
本研究的局限性在于仅研究了焦虑雄性动物的mPFC-PAG的变化和调节。
总体而言，我们的研究结果表明，编码效价的mPFC-PAG回路调节焦虑，并且这些投射可能是治疗焦虑症的潜在靶点。
