A midbrain circuit mechanism for noise-induced negative valence coding

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 and Hongbin Yang ()
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Siyao Zhou: Zhejiang University School of Medicine
Yuebin Zhu: Zhejiang University School of Medicine
Ana Du: Zhejiang University School of Medicine
Shuai Niu: Zhejiang University School of Medicine
Yonglan Du: Zhejiang University School of Medicine
Yan Yang: Zhejiang University School of Medicine
Wenqiang Chen: Harvard Medical School
Siyu Du: Zhejiang University School of Medicine
Li Sun: Zhejiang University School of Medicine
Yijun Liu: Zhejiang University School of Medicine
Hangjun Wu: Zhejiang University
Huifang Lou: Zhejiang University School of Medicine
Xiao-Ming Li: Zhejiang University
Shumin Duan: Zhejiang University School of Medicine
Hongbin Yang: Zhejiang University School of Medicine

Nature Communications, 2025, vol. 16, issue 1, 1-17

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-59956-z

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