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