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

Samer Masri, Todd M. Mowery, Regan Fair, Dan H. Sanes

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Article numbere2311570121
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number24
StatePublished - Jun 11 2024


  • auditory cortex
  • critical period
  • hearing loss
  • inhibition
  • parvalbumin

ASJC Scopus subject areas

  • General


Dive into the research topics of 'Developmental hearing loss-induced perceptual deficits are rescued by genetic restoration of cortical inhibition'. Together they form a unique fingerprint.

Cite this