Abstract
Neurons at higher stages of sensory processing can partially compensate for a sudden drop in peripheral input through a homeostatic plasticity process that increases the gain on weak afferent inputs. Even after a profound unilateral auditory neuropathy where >95% of afferent synapses between auditory nerve fibers and inner hair cells have been eliminated with ouabain, central gain can restore cortical processing and perceptual detection of basic sounds delivered to the denervated ear. In this model of profound auditory neuropathy, auditory cortex (ACtx) processing and perception recover despite the absence of an auditory brainstem response (ABR) or brainstem acoustic reflexes, and only a partial recovery of sound processing at the level of the inferior colliculus (IC), an auditory midbrain nucleus. In this study, we induced a profound cochlear neuropathy with ouabain and asked whether central gain enabled a compensatory plasticity in the auditory thalamus comparable to the full recovery of function previously observed in the ACtx, the partial recovery observed in the IC, or something different entirely. Unilateral ouabain treatment in adult mice effectively eliminated the ABR, yet robust sound-evoked activity persisted in a minority of units recorded from the contralateral medial geniculate body (MGB) of awake mice. Sound driven MGB units could decode moderate and high-intensity sounds with accuracies comparable to sham-treated control mice, but low-intensity classification was near chance. Pure tone receptive fields and synchronization to broadband pulse trains also persisted, albeit with significantly reduced quality and precision, respectively. MGB decoding of temporally modulated pulse trains and speech tokens were both greatly impaired in ouabain-treated mice. Taken together, the absence of an ABR belied a persistent auditory processing at the level of the MGB that was likely enabled through increased central gain. Compensatory plasticity at the level of the auditory thalamus was less robust overall than previous observations in cortex or midbrain. Hierarchical differences in compensatory plasticity following sensorineural hearing loss may reflect differences in GABA circuit organization within the MGB, as compared to the ACtx or IC.
Highlights
Perception of environmental stimuli arises from the spatiotemporal patterning of spiking at higher stages of sensory processing (Logothetis and Schall, 1989; DeAngelis et al, 1998; Romo et al, 1998)
One month after cochlear denervation, distortion product otoacoustic emissions (DPOAE) thresholds were indistinguishable between the sham and ouabain-treated mice (Figure 1A, one-way analysis of variance (ANOVA), F(1) = 1.6, p = 0.33; ouabain treated n = 6, sham treated n = 4), indicating that hair cell-dependent cochlear amplification was unaffected by ouabain
Thresholds for wave 1b of the auditory brainstem response (ABR) were elevated by an average of 38.2 dB after ouabain treatment (Figure 1B, ANOVA, F(1) = 244.7, p < 0.0001), and wave 1b amplitudes were greatly attenuated (Figure 1C, ANOVA, F(1) = 90.07, p = 0.0002), indicating a profound cochlear neuropathy
Summary
Perception of environmental stimuli arises from the spatiotemporal patterning of spiking at higher stages of sensory processing (Logothetis and Schall, 1989; DeAngelis et al, 1998; Romo et al, 1998). The balance of excitation and inhibition tips toward hyperexcitability throughout the central auditory neuroaxis, increasing the ‘‘central gain’’ on afferent signals so as to partially compensate for a diminished input from the auditory periphery. Central gain cannot fully compensate for the loss of cochlear processing. Dynamic central gain at higher stations of auditory processing may contribute in significant ways to sound perception in both normal and pathological conditions, though the underlying mechanisms and precise linkage to perception have yet to be fully revealed
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