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<p>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 (CIC<sup>glu</sup>) relay noise information to GABAergic neurons in the ventral tegmental area (VTA<sup>GABA</sup>) via the cuneiform nucleus (CnF), encoding negative emotions in mice. In contrast, the CIC<sup>glu</sup>→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 CIC<sup>glu</sup> to convey negative valence to the mesolimbic dopamine system by activating VTA<sup>GABA</sup> neurons. Optogenetic or chemogenetic inhibition of any connection within the CIC<sup>glu</sup>→CnF<sup>glu</sup> → VTA<sup>GABA</sup> 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 CIC<sup>glu</sup>→CnF<sup>glu</sup> → VTA<sup>GABA</sup> circuit in coping with acoustic stressors.</p>

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A midbrain circuit mechanism for noise-induced negative valence coding

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年5月17日

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  • 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

摘要

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.