A midbrain circuit mechanism for noise-induced negative valence coding
Abstract Unpleasant sounds elicit a range of negative emotional reactions, yet the underlying neural mechanisms remain largely unknown. Here we show that glutamatergic neurons in the central inferior colliculus (CICglu) relay noise information to GABAergic neurons in the ventral tegmental area (VTAG...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59956-z |
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| author | Siyao Zhou Yuebin Zhu Ana Du Shuai Niu Yonglan Du Yan Yang Wenqiang Chen Siyu Du Li Sun Yijun Liu Hangjun Wu Huifang Lou Xiao-Ming Li Shumin Duan Hongbin Yang |
| author_facet | Siyao Zhou Yuebin Zhu Ana Du Shuai Niu Yonglan Du Yan Yang Wenqiang Chen Siyu Du Li Sun Yijun Liu Hangjun Wu Huifang Lou Xiao-Ming Li Shumin Duan Hongbin Yang |
| author_sort | Siyao Zhou |
| collection | DOAJ |
| description | Abstract Unpleasant sounds elicit a range of negative emotional reactions, yet the underlying neural mechanisms remain largely unknown. Here we show that glutamatergic neurons in the central inferior colliculus (CICglu) relay noise information to GABAergic neurons in the ventral tegmental area (VTAGABA) via the cuneiform nucleus (CnF), encoding negative emotions in mice. In contrast, the CICglu→medial geniculate (MG) canonical auditory pathway processes salient stimuli. By combining viral tracing, calcium imaging, and optrode recording, we demonstrate that the CnF acts downstream of CICglu to convey negative valence to the mesolimbic dopamine system by activating VTAGABA neurons. Optogenetic or chemogenetic inhibition of any connection within the CICglu→CnFglu → VTAGABA circuit, or direct excitation of the mesolimbic dopamine (DA) system is sufficient to alleviate noise-induced negative emotion perception. Our findings highlight the significance of the CICglu→CnFglu → VTAGABA circuit in coping with acoustic stressors. |
| format | Article |
| id | doaj-art-ea634b8867bd4c8e8e391f11ae8207d0 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-ea634b8867bd4c8e8e391f11ae8207d02025-08-20T03:47:16ZengNature PortfolioNature Communications2041-17232025-05-0116111710.1038/s41467-025-59956-zA midbrain circuit mechanism for noise-induced negative valence codingSiyao Zhou0Yuebin Zhu1Ana Du2Shuai Niu3Yonglan Du4Yan Yang5Wenqiang Chen6Siyu Du7Li Sun8Yijun Liu9Hangjun Wu10Huifang Lou11Xiao-Ming Li12Shumin Duan13Hongbin Yang14Department of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineSection of Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical SchoolDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Pathology of Sir Run Run Shaw Hospital; Center of Cryo-Electron Microscopy, Zhejiang UniversityDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineNHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang UniversityDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineDepartment of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital & Liangzhu Laboratory, Zhejiang University School of MedicineAbstract Unpleasant sounds elicit a range of negative emotional reactions, yet the underlying neural mechanisms remain largely unknown. Here we show that glutamatergic neurons in the central inferior colliculus (CICglu) relay noise information to GABAergic neurons in the ventral tegmental area (VTAGABA) via the cuneiform nucleus (CnF), encoding negative emotions in mice. In contrast, the CICglu→medial geniculate (MG) canonical auditory pathway processes salient stimuli. By combining viral tracing, calcium imaging, and optrode recording, we demonstrate that the CnF acts downstream of CICglu to convey negative valence to the mesolimbic dopamine system by activating VTAGABA neurons. Optogenetic or chemogenetic inhibition of any connection within the CICglu→CnFglu → VTAGABA circuit, or direct excitation of the mesolimbic dopamine (DA) system is sufficient to alleviate noise-induced negative emotion perception. Our findings highlight the significance of the CICglu→CnFglu → VTAGABA circuit in coping with acoustic stressors.https://doi.org/10.1038/s41467-025-59956-z |
| spellingShingle | Siyao Zhou Yuebin Zhu Ana Du Shuai Niu Yonglan Du Yan Yang Wenqiang Chen Siyu Du Li Sun Yijun Liu Hangjun Wu Huifang Lou Xiao-Ming Li Shumin Duan Hongbin Yang A midbrain circuit mechanism for noise-induced negative valence coding Nature Communications |
| title | A midbrain circuit mechanism for noise-induced negative valence coding |
| title_full | A midbrain circuit mechanism for noise-induced negative valence coding |
| title_fullStr | A midbrain circuit mechanism for noise-induced negative valence coding |
| title_full_unstemmed | A midbrain circuit mechanism for noise-induced negative valence coding |
| title_short | A midbrain circuit mechanism for noise-induced negative valence coding |
| title_sort | midbrain circuit mechanism for noise induced negative valence coding |
| url | https://doi.org/10.1038/s41467-025-59956-z |
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