Cortical PV interneurons regulate loudness perception and sustainably reverse loudness hypersensitivity.

Summary

PV interneurons act as a 'volume knob' in the auditory cortex, bi-directionally tuning sensitivity to sound level. A single bout of 40 Hz PVN stimulation durably dampened cortical responsiveness and desensitized mice to loudness. In a new adult-onset hyperacusis model, minutes of 40 Hz stimulation reversed cortical hyperactivity and restored normal loudness sensitivity for a week.

Key findings

• PV interneurons adjust perceptual sound-level sensitivity over a ~20 dB range.
• 40 Hz (gamma) PVN stimulation produces 'sticky', long-lasting gain reduction; 1 Hz and 70 Hz do not.
• A restricted cochlear lesion produces cortical hyperactivity, PVN hypofunction, and loudness hypersensitivity.
• Patterned cortical stimulation reversed a perceptual disorder caused by permanent peripheral injury.