Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition.

Even a transient period of hearing loss during the developmental critical period can induce long-lasting deficits in temporal and spectral perception. These perceptual deficits correlate with speech perception in humans. In gerbils, these 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. Therefore, we developed viral vectors to express proteins that would upregulate gerbil postsynaptic inhibitory receptor subunits (GABAA, Gabra1; GABAB, Gabbr1b) in pyramidal neurons, and an enzyme that mediates GABA synthesis (GAD65) presynaptically in parvalbumin-expressing interneurons. A transient period of developmental hearing loss during the auditory critical period significantly impaired perceptual performance on two auditory tasks: amplitude modulation depth detection and spectral modulation depth detection. We then tested the capacity of each vector to restore perceptual performance on these auditory tasks. While both GABA receptor vectors increased the amplitude of cortical inhibitory postsynaptic potentials, only viral expression of postsynaptic GABAB receptors improved perceptual thresholds to control levels. Similarly, presynaptic GAD65 expression improved perceptual performance on spectral modulation detection. These findings suggest that recovering performance on auditory perceptual tasks depends on GABAB receptor-dependent transmission at the auditory cortex parvalbumin to pyramidal synapse and point to potential therapeutic targets for developmental sensory disorders.

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

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.