Abstract
Tinnitus and hyperacusis are life-disrupting perceptual abnormalities that are often preceded by acoustic overexposure. Animal models of overexposure have suggested a link between these phenomena and neural hyperactivity, i.e., elevated spontaneous rates (SRs) and sound-evoked responses. Prior work has focused on changes in central auditory responses, with less attention paid to the exact nature of the associated cochlear damage. The demonstration that acoustic overexposure can cause cochlear neuropathy without permanent threshold elevation suggests cochlear neuropathy per se may be a key elicitor of neural hyperactivity. We addressed this hypothesis by recording responses in the mouse inferior colliculus (IC) following a bilateral, neuropathic noise exposure. One to three weeks post-exposure, mean SRs were unchanged in mice recorded while awake, or under anesthesia. SRs were also unaffected by more intense, or unilateral exposures. These results suggest that neither neuropathy nor hair cell loss are sufficient to raise SRs in the IC, at least in 7-week-old mice, 1–3 weeks post exposure. However, it is not clear whether our mice had tinnitus. Tone-evoked rate-level functions at the CF were steeper following exposure, specifically in the region of maximal neuropathy. Furthermore, suppression driven by off-CF tones and by ipsilateral noise were reduced. Both changes were especially pronounced in neurons of awake mice. This neural hypersensitivity may manifest as behavioral hypersensitivity to sound – prior work reports that this same exposure causes elevated acoustic startle. Together, these results indicate that neuropathy may initiate a compensatory response in the central auditory system leading to the genesis of hyperacusis.
Highlights
Tinnitus, the perception of sounds in silence, is often preceded by acoustic overexposure (Eggermont and Roberts, 2004), neurophysiological studies of tinnitus have focused on noise-induced changes in spontaneous discharge
This exposure resulted in a 40–50% loss of synapses between inner hair cells and auditory nerve fibers in the basal half of the cochlea (Figure 1A)
Tinnitus and hyperacusis often occur following an episode of noise exposure, and often begin immediately post exposure (Meikle, 1997; Holgers and Pettersson, 2005; Daniel, 2007)
Summary
The perception of sounds in silence, is often preceded by acoustic overexposure (Eggermont and Roberts, 2004), neurophysiological studies of tinnitus have focused on noise-induced changes in spontaneous discharge. Elevated SRs and behavioral evidence for tinnitus have been observed in noise-exposed animals without permanent threshold shift (PTS; Bauer et al, 2008; Koehler and Shore, 2013). Moderate noise exposures that do not cause hair cell damage or PTS can destroy synapses between cochlear hair cells and auditory nerve terminals (Kujawa and Liberman, 2009). Such cochlear neuropathy does not affect audiometric thresholds, but reduces suprathreshold-evoked response amplitudes, such as the auditory brainstem response (ABR; Bharadwaj et al, 2015; Shaheen et al, 2015). Since tinnitus patients with normal thresholds have reduced ABR amplitudes (Gu et al, 2012), cochlear neuropathy may play a key role in the genesis of central spontaneous hyperactivity and tinnitus
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