A midbrain circuit mechanism for noise-induced negative valence coding.

Area of Science:

• Neuroscience
• Auditory processing
• Emotion regulation

Background:

• Unpleasant sounds trigger negative emotions, but the brain mechanisms are unclear.
• The central auditory pathway's role in negative emotional responses to noise is not well understood.

Purpose of the Study:

• To elucidate the neural circuit underlying negative emotional reactions to unpleasant sounds in mice.
• To differentiate the pathways involved in processing negative valence versus salient auditory stimuli.

Main Methods:

• Viral tracing to map neural connections.
• Calcium imaging to monitor neural activity.
• Optrode recordings to measure neural signals.
• Optogenetic and chemogenetic manipulations to inhibit/excite neural circuits.

Main Results:

• A specific glutamatergic pathway from the central inferior colliculus (CIC^glu) to the ventral tegmental area (VTA^GABA) via the cuneiform nucleus (CnF) encodes negative emotions.
• This pathway, CIC^glu→CnF^glu→VTA^GABA, conveys negative valence to the mesolimbic dopamine system.
• Inhibition of this circuit or excitation of the mesolimbic dopamine system reduced negative emotional responses to noise.

Conclusions:

• The CIC^glu→CnF^glu→VTA^GABA circuit is critical for processing the negative emotional impact of acoustic stressors.
• This pathway is distinct from the canonical auditory pathway (CIC^glu→MG) that processes salient stimuli.
• Targeting this circuit offers potential therapeutic avenues for managing negative responses to noise.