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bioRxiv · 10.1101/2023.03.24.534013

Cortical contributions to the perception of loudness and hyperacusis

McGill, M.·Kremer, C.·Stecyk, K.·Clayton, K.·Skerleva, D.·Hancock, K.·Kujawa, S. G.·Polley, D. B.
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Abstract

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.

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McGill, M., Kremer, C., Stecyk, K., Clayton, K., Skerleva, D., Hancock, K., Kujawa, S. G., Polley, D. B.. 2023-03-25. Cortical contributions to the perception of loudness and hyperacusis. https://doi.org/10.1101/2023.03.24.534013

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