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A midbrain circuit mechanism for noise-induced negative valence coding

Author

Listed:
  • Siyao Zhou

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Yuebin Zhu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Ana Du

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Shuai Niu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Yonglan Du

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Yan Yang

    (Zhejiang University School of Medicine)

  • Wenqiang Chen

    (Harvard Medical School
    Steno Diabetes Center Copenhagen)

  • Siyu Du

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Li Sun

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Yijun Liu

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Hangjun Wu

    (Zhejiang University)

  • Huifang Lou

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Xiao-Ming Li

    (Zhejiang University
    Zhejiang University School of Medicine
    Nanhu Brain-Computer Interface Institute)

  • Shumin Duan

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

  • Hongbin Yang

    (Zhejiang University School of Medicine
    Zhejiang University
    Zhejiang University)

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.

Suggested Citation

  • 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, 2025. "A midbrain circuit mechanism for noise-induced negative valence coding," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59956-z
    DOI: 10.1038/s41467-025-59956-z
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