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J Neurosci. 2019 Aug 26. pii: 0749-19. doi: 10.1523/JNEUROSCI.0749-19.2019. [Epub ahead of print]

Preserving inhibition during developmental hearing loss rescues auditory learning and perception.

Author information

1
Center for Neural Science, New York University, 4 Washington Place, New York,NY 10003 tm106@nyu.edu.
2
Center for Neural Science, New York University, 4 Washington Place, New York,NY 10003.
3
Stanley Center for Psychiatric Research. The Broad Institute of MIT and Harvard, 75 Ames Street, Boston, MA 02142.
4
Department of Neurobiology, Harvard Medical School, 220 Longwood Ave., Boston, MA 02115.
5
Department of Psychology, New York University.
6
Department of Biology, New York University.
7
Neuroscience Institute at NYU Langone School of Medicine.

Abstract

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 central nervous system. 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 inhibitory postsynaptic potentials (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.SIGNIFICANCE STATEMENTEven a temporary period of childhood hearing loss can induce communication deficits that persist long after auditory thresholds return to normal. These deficits may arise from long-lasting central impairments, including the loss of synaptic inhibition. Here, we asked whether hearing loss-induced behavioral deficits could be reversed by reinstating normal inhibitory strength. Gerbils reared with transient hearing loss displayed both learning and perceptual deficits. However, when animals were treated with a selective GABA reuptake inhibitor during or after hearing loss, behavioral deficits were entirely corrected. This behavioral recovery was correlated with the return of normal thalamic and cortical inhibitory function. Thus, some perceptual and cognitive deficits induced by developmental hearing loss were prevented with a treatment that rescues a central synaptic property.

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