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

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 GABA 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.

Neural Plastic Changes in the Subcortical Auditory Neural Pathway after Single-Sided Deafness in Adult Mice: A MEMRI Study

“…No significant difference in Mn 2+ SI was found in the AC or MG. Consistent with the present results, some studies have reported comparable auditory neural activities in the AC after SSD [7, 22, 23]. No difference in 2-DG uptake is observed in the AC 3 weeks after unilateral cochlear ablation in gerbils [7].…”

“…Because integrations of temporal and spectral information of sound and binaural summation are processed in the higher auditory neural system, the differences in Mn 2+ SI might be diluted in the MG and AC. Cortical reorganization, which accompanies the increase in excitatory receptor (AMPA) and the decrease in inhibitory receptor (GABA A ), leads to the homeostatic neural activity in AC following a month of SSD in mice [23]. The aberrant functional coupling of AC corticofugal neurons with other brain areas, besides the auditory brainstem, is reportedly increased for two weeks following noise-induced hearing loss in mice, according to calcium imaging [25].…”

Developmental PCB exposure disrupts synaptic transmission and connectivity in the rat auditory cortex, independent of its effects on peripheral hearing threshold

“…Increases of spontaneous IPSC amplitude and frequency seen in PCB-exposed subjects were unexpected and contrast previous findings of reduced central inhibition following hearing loss (Bledsoe et al, 1995;Vale and Sanes, 2002;Kotak et al, 2005;Sarro et al, 2008;Balaram et al, 2019). Several differences between PCB-induced hearing loss and aforementioned studies may explain differences in the outcomes.…”

“…Hearing loss, when experimentally induced by high level sound exposure, cochlear ablation, or administration of an ototoxic agent, drives plasticity in central auditory structures, weakening inhibitory connections, strengthening excitatory connections, and increasing excitability and spontaneous firing, and these changes generally occur over the course of weeks (Bledsoe et al, 1995;Wang et al, 2002;Vale and Sanes, 2002;Kotak et al, 2005;Sarro et al, 2008;Yang et al, 2012;Chambers et al, 2016;Balaram et al 2019). These changes effectively increase the gain of the central auditory system and may serve a homeostatic role in restoring central auditory processing after a loss of sensory input (Noreña, 2011;Zeng, 2013;Chambers et al, 2016).…”

Silence, Solitude, and Serotonin: Neural Mechanisms Linking Hearing Loss and Social Isolation

“…The loss of input from the auditory periphery triggers a cascade of plasticity within the central auditory system, multiple aspects of which have been extensively reviewed. Following peripheral loss, the central auditory system undergoes a progressive rebalancing of excitation versus inhibition and synaptic plasticity that encompasses both ascending and descending systems (e.g., [ 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 ]). As a result of this rebalancing, the gain of local auditory potentials increases as auditory pathways ascend [ 28 , 29 ].…”