Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit
Abstract Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal cortex (mPFC) via t...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-56258-2 |
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| author | Zhihua Luo Junlin Chen Yuchu Liu Yelin Dai Hui Gao Borui Zhang Haibin Ou Kwok-Fai So Ji-an Wei Li Zhang |
| author_facet | Zhihua Luo Junlin Chen Yuchu Liu Yelin Dai Hui Gao Borui Zhang Haibin Ou Kwok-Fai So Ji-an Wei Li Zhang |
| author_sort | Zhihua Luo |
| collection | DOAJ |
| description | Abstract Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal cortex (mPFC) via the ventromedial thalamic (VM) nuclei in male mice. Besides anatomical evidence, both ex vivo and in vivo recordings showed enhanced excitability of M1-VM inputs to the prelimbic (PrL) region of mPFC upon 14-day treadmill exercise on a chronic restraint stress (CRS) mouse model. Further functional interrogations demonstrated that the activation of this neural circuit is both necessary and sufficient to direct the anxiolytic effect of exercise training in CRS mice. Our findings provide more insights into the neural circuits connecting motor and mental regions under exercise paradigm and implicate potential targets for neuromodulation in treating anxiety disorders. |
| format | Article |
| id | doaj-art-25caf23810e94165a6a3d0e73ab7d3c9 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-25caf23810e94165a6a3d0e73ab7d3c92025-01-26T12:42:14ZengNature PortfolioNature Communications2041-17232025-01-0116111410.1038/s41467-025-56258-2Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuitZhihua Luo0Junlin Chen1Yuchu Liu2Yelin Dai3Hui Gao4Borui Zhang5Haibin Ou6Kwok-Fai So7Ji-an Wei8Li Zhang9Key Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityCollege of Life Science and Technology, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityKey Laboratory of CNS Regeneration (Ministry of Education), Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityAbstract Physical exercise effectively prevents anxiety disorders caused by environmental stress. The neural circuitry mechanism, however, remains incomplete. Here, we identified a previously unrecognized pathway originating from the primary motor cortex (M1) to medial prefrontal cortex (mPFC) via the ventromedial thalamic (VM) nuclei in male mice. Besides anatomical evidence, both ex vivo and in vivo recordings showed enhanced excitability of M1-VM inputs to the prelimbic (PrL) region of mPFC upon 14-day treadmill exercise on a chronic restraint stress (CRS) mouse model. Further functional interrogations demonstrated that the activation of this neural circuit is both necessary and sufficient to direct the anxiolytic effect of exercise training in CRS mice. Our findings provide more insights into the neural circuits connecting motor and mental regions under exercise paradigm and implicate potential targets for neuromodulation in treating anxiety disorders.https://doi.org/10.1038/s41467-025-56258-2 |
| spellingShingle | Zhihua Luo Junlin Chen Yuchu Liu Yelin Dai Hui Gao Borui Zhang Haibin Ou Kwok-Fai So Ji-an Wei Li Zhang Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit Nature Communications |
| title | Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| title_full | Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| title_fullStr | Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| title_full_unstemmed | Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| title_short | Treadmill exercise prevents stress-induced anxiety-like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| title_sort | treadmill exercise prevents stress induced anxiety like behaviors via enhancing the excitatory input from the primary motor cortex to the thalamocortical circuit |
| url | https://doi.org/10.1038/s41467-025-56258-2 |
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