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bioRxiv · 10.1101/2023.01.10.523440

Developmental hearing loss-induced perceptual deficits are rescued by cortical expression of GABAB receptors

Masri, S.·Fair, R.·Mowery, T. M.·Sanes, D. H.
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Abstract

Even transient periods of developmental hearing loss during the developmental critical period have been linked to long-lasting deficits in auditory perception, including temporal and spectral processing, which correlate with speech perception and educational attainment. In gerbils, hearing loss-induced perceptual deficits are correlated with a reduction of both ionotropic GABAA and metabotropic GABAB receptor-mediated synaptic inhibition in auditory cortex, but most research on critical period plasticity has focused on GABAA receptors. We developed viral vectors to express both endogenous GABAA or GABAB receptor subunits in auditory cortex and tested their capacity to restore perception of temporal and spectral auditory cues following critical period hearing loss in the Mongolian gerbil. HL significantly impaired perception of both temporal and spectral auditory cues. While both vectors similarly increased IPSCs in auditory cortex, only overexpression of GABAB receptors improved perceptual thresholds after HL to be similar to those of animals without developmental hearing loss. These findings identify the GABAB receptor as an important regulator of sensory perception in cortex and point to potential therapeutic targets for developmental sensory disorders. Significance StatementHearing loss in children can induce deficits in aural communication that persevere even after audibility has returned to normal, suggesting permanent changes to the auditory central nervous system. In fact, a reduction in cortical synaptic inhibition has been implicated in a broad range of developmental disorders, including hearing loss. Here, we tested the hypothesis that developmental hearing loss-induced perceptual impairments in gerbils are caused by a permanent reduction of auditory cortical inhibitory synapse strength. We found that virally-mediated expression of a GABAB receptor subunit in gerbil auditory cortex was able to restore two auditory perceptual skills in juvenile animals reared with hearing loss, suggesting that cortical synaptic inhibition is a plausible therapeutic target for sensory processing disorders.

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Masri, S., Fair, R., Mowery, T. M., Sanes, D. H.. 2023-01-10. Developmental hearing loss-induced perceptual deficits are rescued by cortical expression of GABAB receptors. https://doi.org/10.1101/2023.01.10.523440

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