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

Area of Science:

• Neuroscience
• Auditory system research
• Cortical circuit function

Background:

• Parvalbumin-expressing neurons (PVNs) are crucial for stabilizing cortical activity, generating gamma rhythms, and modulating plasticity.
• PVNs in the auditory cortex (ACtx) regulate neural and perceptual sensitivity to sound levels.
• Dysfunction of PVNs is implicated in sensory disorders like hyperacusis.

Purpose of the Study:

• To investigate the role of PVNs in auditory processing and sound level perception.
• To explore the potential of patterned PVN stimulation for treating sensory deficits.
• To establish and investigate a mouse model of adult-onset hyperacusis.

Main Methods:

• Utilized in vivo electrophysiology and behavioral assays in mice.
• Investigated PVN function in the auditory cortex (ACtx) using optogenetic stimulation.
• Developed a noise-induced cochlear lesion model to mimic hyperacusis.

Main Results:

• PVNs act as a "volume knob," bi-directionally adjusting neural and perceptual sensitivity to sound.
• 40 Hz PVN stimulation induced sustained dampening of ACtx sound responsiveness and behavioral desensitization to loudness.
• Noise-induced cochlear lesions led to ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity.
• 40 Hz PVN stimulation in noise-exposed mice reversed ACtx hyperactivity and restored normal loudness sensitivity for one week.

Conclusions:

• Patterned 40 Hz stimulation of PVNs offers a potential therapeutic strategy for sensory disorders.
• Cortical circuit stimulation can reverse perceptual deficits caused by permanent peripheral injuries.
• PVN function is critical for normal auditory perception and loudness regulation.