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Neuroscience. 2019 May 21;407:108-119. doi: 10.1016/j.neuroscience.2018.08.023. Epub 2018 Sep 1.

Synergistic Transcriptional Changes in AMPA and GABAA Receptor Genes Support Compensatory Plasticity Following Unilateral Hearing Loss.

Author information

1
Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114, USA; Dept. of Otolaryngology, Harvard Medical School, Boston MA 02114, USA.
2
Dept. of Hearing and Speech Sciences, Vanderbilt Bill Wilkerson Center for Otolaryngology and Communication Sciences, Vanderbilt University Medical Center, Nashville TN 37232 USA.
3
Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston MA 02114, USA; Dept. of Otolaryngology, Harvard Medical School, Boston MA 02114, USA. Electronic address: daniel_polley@hms.harvard.edu.

Abstract

Debilitating perceptual disorders including tinnitus, hyperacusis, phantom limb pain and visual release hallucinations may reflect aberrant patterns of neural activity in central sensory pathways following a loss of peripheral sensory input. Here, we explore short- and long-term changes in gene expression that may contribute to hyperexcitability following a sudden, profound loss of auditory input from one ear. We used fluorescence in situ hybridization to quantify mRNA levels for genes encoding AMPA and GABAA receptor subunits (Gria2 and Gabra1, respectively) in single neurons from the inferior colliculus (IC) and auditory cortex (ACtx). Thirty days after unilateral hearing loss, Gria2 levels were significantly increased while Gabra1 levels were significantly decreased. Transcriptional rebalancing was more pronounced in ACtx than IC and bore no obvious relationship to the degree of hearing loss. By contrast to the opposing, synergistic shifts in Gria2 and Gabra1 observed 30 days after hearing loss, we found that transcription levels for both genes were equivalently reduced after 5 days of hearing loss, producing no net change in the excitatory/inhibitory transcriptional balance. Opposing transcriptional shifts in AMPA and GABA receptor genes that emerge several weeks after a peripheral insult could promote both sensitization and disinhibition to support a homeostatic recovery of neural activity following auditory deprivation. Imprecise transcriptional changes could also drive the system toward perceptual hypersensitivity, degraded temporal processing and the irrepressible perception of non-existent environmental stimuli, a trio of perceptual impairments that often accompany chronic sensory deprivation.

KEYWORDS:

auditory neuropathy; gene transcription; hearing loss; homeostatic plasticity; hyperacusis; tinnitus

PMID:
30176318
PMCID:
PMC6395571
[Available on 2020-05-21]
DOI:
10.1016/j.neuroscience.2018.08.023
[Indexed for MEDLINE]

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