A midbrain circuit mechanism for noise-induced negative valence coding
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.
Authors
- Shumin Duan (ORCID: https://orcid.org/0000-0002-0466-1821)
- Yu Zhu (ORCID: https://orcid.org/0000-0001-8961-0136)
- Yan Yang (ORCID: https://orcid.org/0000-0003-3001-9178)
- Yong-lan Du
- Yijun Liu (ORCID: https://orcid.org/0000-0001-6553-1484)
- Siyao Zhou
- Huifang Lou (ORCID: https://orcid.org/0000-0002-1793-9458)
- Xiao‐Ming Li (ORCID: https://orcid.org/0000-0002-8617-1702)
- Wenqiang Chen (ORCID: https://orcid.org/0009-0006-6864-9932)
- Hongbin Yang (ORCID: https://orcid.org/0000-0001-8574-1542)
- Li Sun (ORCID: https://orcid.org/0000-0001-8009-1296)
- S. X. Du (ORCID: https://orcid.org/0009-0005-2449-0678)
- Shuai Niu (ORCID: https://orcid.org/0000-0002-9358-4572)
- Ana Du
- Hangjun Wu
Institutions
- Zhejiang Chinese Medical University (CN)
- Joslin Diabetes Center (US)
- Allen Institute for Brain Science (US)
- Steno Diabetes Centers (DK)
- Harvard University (US)
- Sir Run Run Shaw Hospital (CN)
- Zhejiang Lab (CN)
- Hangzhou Seventh Peoples Hospital (CN)
- Second Affiliated Hospital of Zhejiang University (CN)
- Zhejiang University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-17
- DOI
- https://doi.org/10.1038/s41467-025-59956-z
- Primary Topic
- Neural dynamics and brain function
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- National Natural Science Foundation of China
- Zhejiang University
- Chinese Academy of Medical Sciences
- University of California, San Francisco
- Natural Science Foundation of Zhejiang Province