Elsevier

Hearing Research

Volume 331, January 2016, Pages 47-56
Hearing Research

Research paper
The immediate effects of acoustic trauma on excitation and inhibition in the inferior colliculus: A Wiener-kernel analysis

https://doi.org/10.1016/j.heares.2015.10.007Get rights and content

Highlights

  • Wiener kernels were used to study excitation and inhibition in the inferior colliculus.

  • Acoustic trauma resulted in the loss of both excitatory and inhibitory components in high-CF units.

  • Units tuned to frequencies within two octaves below the trauma frequency retained an excitatory response but lost inhibition.

  • Reduced inhibition in the inferior colliculus may contribute to immediate noise-induced tinnitus and hyperacusis.

Abstract

Noise-induced tinnitus and hyperacusis are thought to correspond to a disrupted balance between excitation and inhibition in the central auditory system. Excitation and inhibition are often studied using pure tones; however, these responses do not reveal inhibition within the excitatory pass band. Therefore, we used a Wiener-kernel analysis, complemented with singular value decomposition (SVD), to investigate the immediate effects of acoustic trauma on excitation and inhibition in the inferior colliculus (IC).

Neural responses were recorded from the IC of three anesthetized albino guinea pigs before and immediately after a one-hour bilateral exposure to an 11-kHz tone of 124 dB SPL. Neural activity was recorded during the presentation of a 1-h continuous 70 dB SPL Gaussian-noise stimulus. Spike trains were subjected to Wiener-kernel analysis in which the second-order kernel was decomposed into excitatory and inhibitory components using SVD.

Hearing thresholds between 3 and 22 kHz were elevated (13–47 dB) immediately after acoustic trauma. The presence and frequency tuning of excitation and inhibition in units with a low characteristic frequency (CF; < 3 kHz) was not affected, inhibition disappeared whereas excitation was not affected in mid-CF units (3 < CF < 11 kHz), and both excitation and inhibition disappeared in high-CF units (CF > 11 kHz). This specific differentiation could not be identified by tone-evoked receptive-field analysis, in which inhibitory responses disappeared in all units, along with excitatory responses in high-CF units.

This study is the first to apply Wiener-kernel analysis, complemented with SVD, to study the effects of acoustic trauma on spike trains derived from the IC. With this analysis, a reduction of inhibition and preservation of good response thresholds was shown in mid-CF units immediately after acoustic trauma. These neurons may mediate noise-induced tinnitus and/or hyperacusis. Moreover, an immediate profound high-frequency hearing loss was reflected by reduced evoked firing rates and loss of both excitation and inhibition in high-CF units.

Introduction

Exposure to loud sounds may result in tinnitus, the perception of a sound in the absence of an external sound source, and/or hyperacusis, the reduced tolerance of, and increased sensitivity to, sounds with normal intensities. Among young adults, 89.5% report experiencing transient tinnitus immediately after exposure to loud music (Gilles et al., 2012). The prevalence of hyperacusis in adults lies between 8% and 16% (Tyler et al., 2014). Both tinnitus and hyperacusis can be severely debilitating conditions for which there are no widespread, effective treatments.

Extensive acoustic overstimulation affects the balance between excitation and inhibition in the inferior colliculus (IC). In particular, acoustic trauma may shift the excitation/inhibition balance towards excitation. This is shown by a downregulation of genes associated with inhibitory neurotransmission (Dong et al., 2010) and by a reduction of the number of units showing an inhibitory response to pure tones following acoustic trauma (Heeringa and van Dijk, 2014). The resulting imbalance between excitation and inhibition is thought to be an underlying mechanism of noise-induced tinnitus and hyperacusis (Noreña, 2011, Knipper et al., 2013).

The functional relationship between excitation and inhibition can be studied by investigating tone-evoked firing rates (Boettcher and Salvi, 1993, Heeringa and van Dijk, 2014). Inhibitory responses are usually defined as a decrease in spontaneous firing rate during a certain tone, which is typically found along the edges of the excitatory receptive field. However, the response to a tone within the excitatory receptive field of a neuron may also be the net result of an excitatory and an inhibitory component. These components cannot be separated by studying responses to tones, unless excitation and inhibition are clearly separated in time.

Wiener-kernel analysis is a technique that is able to disentangle inhibition that is hidden within the excitatory passband (Eggermont, 1993, van Dijk et al., 1997, Yamada and Lewis, 1999, Temchin et al., 2005, van Dijk et al., 2011). To apply this analysis, neural responses from the auditory system to broadband Gaussian noise are measured. A set of Wiener kernels are obtained by calculating the first- and second-order cross correlation of the broadband noise with the noise-evoked spike train. These kernels characterize the linear and nonlinear responses of the auditory system up to the location where the response was measured. In order to separate excitatory and inhibitory contributions, a singular value decomposition (SVD) can be applied to decompose the second-order kernel into a number of parallel subsystems (Yamada and Lewis, 1999). Each subsystem is characterized by a filter function (an eigenvector of the kernel matrix) and a gain function (the corresponding eigenvalue; see Fig. 1). Eigenvalues can be positive or negative, reflecting excitatory and inhibitory subsystems, respectively. As such, the Wiener-kernel analysis, complemented with SVD, allows us to separate relative contributions of excitation and inhibition in a noise-evoked neural signal in a subject-centered manner, which makes this method suitable to further elucidate and characterize properties of a noise-induced disturbed balance between excitation and inhibition. Wiener-kernel analyses have previously been applied to responses of the auditory nerve and the cochlear nucleus (e.g. van Dijk et al., 1994, Lewis et al., 2002a, Lewis et al., 2002b, Recio-Spinoso and van Dijk, 2006). Furthermore, noise-based spectro-temporal receptive fields, second-order cross correlations that are similar to the second-order Wiener kernel (Eggermont, 1993), have been recorded from the auditory midbrain of the grass frog and from the IC of the cat (Hermes et al., 1981, Escabí and Schreiner, 2002).

The current study aimed at investigating the immediate consequences of acoustic trauma on excitation and inhibition in the IC, by studying the excitatory and inhibitory subsystems as derived from SVD of second-order Wiener kernels. The electrode, which yield recordings from 16 channels simultaneously, remained in the IC during acoustic trauma, which enabled us to assess the functional properties of excitation and inhibition from the same multi-units before and after trauma.

Section snippets

Animals

Three male albino guinea pigs (362–406 g; Dunkin Hartley; Harlan Laboratories, Horst, the Netherlands) were anesthetized with ketamine/xylazine (70 mg/kg 10% Ketamine, Alfasan, Woerden-Holland; 6 mg/kg 2% Rompun, Bayer-Healthcare; i.m.). Half the initial dose was applied every hour to maintain a deep level of anesthesia throughout the experiment. A tracheotomy was performed for artificial respiration, a skull screw was placed for fixation of the head, body temperature was kept constant at 38 °C

Results

Data from 33 IC units were used to study the immediate effects of acoustic trauma on central excitation and inhibition. Exposure for 1 h to an 11-kHz tone of 124 dB SPL resulted in elevated ABR thresholds for all measured frequencies. Thresholds for 3 kHz and 6 kHz were both elevated with 13 dB on average (range: 10 dB–20 dB), thresholds for 11 kHz and 22 kHz (tones at and above the trauma frequency) were elevated with 40 dB (range: 35 dB–50 dB) and 47 dB (range: 35 dB–65 dB) on average,

Discussion

This study demonstrated that the balance between excitation and inhibition, as shown through Wiener-kernel analysis, is disrupted immediately after acoustic trauma. The disrupted balance is exclusively apparent in multi units tuned to frequencies up to the trauma frequency (mid-CF units). Additionally, spontaneous and noise-evoked firing rates were decreased and units were tuned to lower frequencies immediately following acoustic trauma. This study is the first to show that a Wiener-kernel

Acknowledgments

The authors want to thank Russ Snyder for showing us the surgical procedures involved in the IC recordings, David Martel for providing valuable suggestions on the English language, and the anonymous reviewers, whose critical reviews have substantially improved the current manuscript.

This work was supported by the Heinsius Houbolt Foundation and the Stichting Gehoorgestoorde Kind. The study is part of the research program of our department: Healthy Aging and Communication.

References (40)

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    Such an increase in E/I ratio is not inconsistent with the previous hypothesis of brainstem dysfunction, as an imbalanced E/I ratio could feasibly serve as the circuit-level substrate of decreased brainstem information transfer or the homeostatic activity up-regulation seen in the IC and/or auditory cortex (McCullagh et al., 2020; Zimmerman et al., 2020). Furthermore, it is quite likely that an increased E/I ratio is responsible for increases in central gain seen in models of hyperacusis elicited by salicylates (G.-D. Chen et al., 2013; Gong et al., 2008; Lu et al., 2011; W. Sun et al., 2009) or acoustic trauma (Heeringa and van Dijk, 2016; Ma et al., 2020; Salvi et al., 2000; Scholl and Wehr, 2008; Wei Sun et al., 2012). A model of increased E/I ratio has long been posited as a common final pathway to explain the core features of autism (Culotta and Penzes, 2020; Foss-Feig et al., 2017; Lee et al., 2017; Nelson and Valakh, 2015; Rubenstein and Merzenich, 2003; Sohal and Rubenstein, 2019) as well as some associated conditions such as epilepsy (Bozzi et al., 2018).

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