Neural signatures of auditory hypersensitivity following acoustic trauma

Abstract

Neurons in sensory cortex exhibit a remarkable capacity to maintain stable firing rates despite large fluctuations in afferent activity levels. However, sudden peripheral deafferentation in adulthood can trigger an excessive, non-homeostatic cortical compensatory response that may underlie perceptual disorders including sensory hypersensitivity, phantom limb pain, and tinnitus. Here, we show that mice with noise-induced damage of the high-frequency cochlear base were behaviorally hypersensitive to spared mid-frequency tones and to direct optogenetic stimulation of auditory thalamocortical neurons. Chronic two-photon calcium imaging from ACtx pyramidal neurons (PyrNs) revealed an initial stage of spatially diffuse hyperactivity, hyper-correlation, and auditory hyperresponsivity that consolidated around deafferented map regions three or more days after acoustic trauma. Deafferented PyrN ensembles also displayed hypersensitive decoding of spared mid-frequency tones that mirrored behavioral hypersensitivity, suggesting that non-homeostatic regulation of cortical sound intensity coding following sensorineural loss may be an underlying source of auditory hypersensitivity. Excess cortical response gain after acoustic trauma was expressed heterogeneously among individual PyrNs, yet 40% of this variability could be accounted for by each cell’s baseline response properties prior to acoustic trauma. PyrNs with initially high spontaneous activity and gradual monotonic intensity growth functions were more likely to exhibit non-homeostatic excess gain after acoustic trauma. This suggests that while cortical gain changes are triggered by reduced bottom-up afferent input, their subsequent stabilization is also shaped by their local circuit milieu, where indicators of reduced inhibition can presage pathological hyperactivity following sensorineural hearing loss.

Distorted neural signal dynamics create hypersensitivity to background noise after hearing loss

“…Such clustering could arise from normal central processing of distorted peripheral inputs, but it is also possible that plastic changes in central processing that follow hearing loss exacerbate the peripheral distortions. Another study that tracked changes in animals following noise overexposure that created high-frequency hearing loss found both neural and behavioral hypersensitivity to frequencies just below those at which the hearing loss was evident 31 . This specific hypersensitivity took several days to evolve and stabilize after the noise exposure and appears to be mediated by particular elements of the local circuitry in auditory cortex.…”

Increased Pyramidal and VIP Neuronal Excitability in Primary Auditory Cortex Directly Correlates with Tinnitus Behavior

“…Noise-exposure used to induce tinnitus in the present study resulted in a permanent threshold shift at frequencies adjacent to the noise-exposure frequency. Accordingly, long-term sensory damage/deprivation is likely to initiate compensatory homeostatic mechanisms generally seen as increased spontaneous and driven activity, bursting and cross-connectivity in cochlear nucleus, inferior colliculus, auditory thalamus and auditory cortex (Brozoski et al ., 2002; Bauer et al ., 2008; Roberts et al ., 2010; Noreña & Farley, 2013; Sedley, 2019; Shore & Wu, 2019; Henton & Tzounopoulos, 2021; Zhai et al ., 2021; McGill et al ., 2022).…”

“…Tinnitus, commonly referred to as ringing in the ears, is believed, in part, to reflect maladaptive plastic changes at various levels of the central auditory pathway as well as in non-auditory cortical areas, limbic and attentional structures. Partial deafferentation due to peripheral damage results in sensory deprivation to central auditory structures (Kujawa & Liberman, 2009; Shore & Wu, 2019; McGill et al ., 2022). Canonical physiologic signs of decreased auditory input, described for tinnitus models, include increased spontaneous activity, increased neural synchrony and increased bursting at multiple levels of the central auditory pathway (Brozoski et al ., 2002; Kaltenbach et al ., 2004; Brozoski & Bauer, 2005; Kaltenbach et al ., 2005; Ma et al ., 2006; Schaette & Kempter, 2006; Bauer et al ., 2008; Roberts et al ., 2010; Noreña, 2011; Auerbach et al ., 2014; Geven et al ., 2014; Kalappa et al ., 2014; Ropp et al ., 2014).…”

Cortical contributions to the perception of loudness and hyperacusis

“…Asterisks denote significant differences between sham and noise exposure with post hoc pairwise comparisons (p < 0.005). PTS data adapted from McGill, et al (2022) (D) Average pre-and post-exposure ABR Wave 1 growth functions to 11.3 kHz tone pips across mice for each group. (E) Relative change in the ABR Wave 1-3 amplitude at 11.3 kHz, evaluated as the area under the ABR growth function compared to the same measure in baseline per mouse, for each exposure group.…”