Kujawa, S. G. | bioRxiv Science

bioRxiv2024

Cortical determinants of loudness perception and auditory hypersensitivity

Parvalbumin-expressing inhibitory neurons (PVNs) stabilize cortical network activity, generate gamma rhythms, and regulate experience-dependent plasticity. Here, we observed that activation or inactivation of PVNs functioned like a volume knob in the mouse auditory cortex (ACtx), turning neural and behavioral classification of sound level up or down over a 20dB range. PVN loudness adjustments were "sticky", such that a single bout of 40Hz PVN stimulation sustainably suppressed ACtx sound responsiveness, potentiated feedforward inhibition, and behaviorally desensitized mice to loudness. Sensory sensitivity is a cardinal feature of autism, aging, and peripheral neuropathy, prompting us to ask whether PVN stimulation can persistently desensitize mice with ACtx hyperactivity, PVN hypofunction, and loudness hypersensitivity triggered by cochlear sensorineural damage. We found that a single 16-minute bout of 40Hz PVN stimulation session restored normal loudness perception for one week, showing that perceptual deficits triggered by irreversible peripheral injuries can be reversed through targeted cortical circuit interventions.

neuroscience↗

bioRxiv2023

Cortical contributions to the perception of loudness and hyperacusis

Sound perception is closely linked to the spatiotemporal patterning of neural activity in the auditory cortex (ACtx). Inhibitory interneurons sculpt the patterns of excitatory ACtx pyramidal neuron activity, and thus play a central role in sculpting the perception of sound. Reduced inhibition from parvalbumin-expressing (PV) inhibitory interneurons and the associated increased gain of sound-evoked pyramidal neuron spike rates are well-established consequences of aging and sensorineural hearing loss. Here, we reasoned that changes in PV-mediated inhibition would directly impact the perception of loudness. We hypothesized that ACtx PV activity could function as a perceptual volume knob, where reduced or elevated PV activity would increase or decrease the perceived loudness of sound, respectively. To test these hypotheses, we developed a two-alternative forced-choice loudness classification task for head-fixed mice and demonstrated that noise-induced sensorineural hearing loss directly caused a [~]10 dB loudness hyperacusis that begins hours after noise-induced sensorineural hearing loss and persists for at least several weeks. Conversely, sounds were perceived as [~]10 dB softer during optogenetic activation of ACtx PV neurons without having any effect on the overall detectability of sound. These data suggest that ACtx PV neurons can bi-directionally control the perceived loudness of sound, presumably via the strength of their inhibition onto local pyramidal neurons. Further, these data identify cortical PV neurons as a target for hyperacusis therapies and demonstrate a direct link between acquired sensorineural hearing loss and loudness hyperacusis.

neuroscience↗