Preserving inhibition during developmental hearing loss rescues auditory learning and perception

Todd M. Mowery, Melissa L. Caras, Syeda I. Hassan, Derek J. Wang, Jordane Dimidschstein, Gord Fishell, Dan H. Sanes

Research output: Contribution to journalArticlepeer-review


Transient periods of childhood hearing loss can induce deficits in aural communication that persist long after auditory thresholds have returned to normal, reflecting long-lasting impairments to the auditory CNS. Here, we asked whether these behavioral deficits could be reversed by treating one of the central impairments: reduction of inhibitory strength. Male and female gerbils received bilateral earplugs to induce a mild, reversible hearing loss during the critical period of auditory cortex development. After earplug removal and the return of normal auditory thresholds, we trained and tested animals on an amplitude modulation detection task. Transient developmental hearing loss induced both learning and perceptual deficits, which were entirely corrected by treatment with a selective GABA reuptake inhibitor (SGRI). To explore the mechanistic basis for these behavioral findings, we recorded the amplitudes of GABAA and GABAB receptor-mediated IPSPs in auditory cortical and thalamic brain slices. In hearing loss-reared animals, cortical IPSP amplitudes were significantly reduced within a few days of hearing loss onset, and this reduction persisted into adulthood. SGRI treatment during the critical period prevented the hearing loss-induced reduction of IPSP amplitudes; but when administered after the critical period, it only restored GABAB receptor-mediated IPSP amplitudes. These effects were driven, in part, by the ability of SGRI to upregulate α1 subunit-dependent GABAA responses. Similarly, SGRI prevented the hearing loss-induced reduction of GABAA and GABAB IPSPs in the ventral nucleus of the medial geniculate body. Thus, by maintaining, or subsequently rescuing, GABAergic transmission in the central auditory thalamocortical pathway, some perceptual and cognitive deficits induced by developmental hearing loss can be prevented.

Original languageEnglish (US)
Pages (from-to)8347-8361
Number of pages15
JournalJournal of Neuroscience
Issue number42
StatePublished - Oct 2019


  • Auditory cortex
  • Auditory perception
  • Hearing loss
  • Plasticity
  • Synaptic inhibition

ASJC Scopus subject areas

  • Neuroscience(all)


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