Skip to main content
NCBI home page
NIHPA Author Manuscripts logoLink to NIHPA Author Manuscripts
. Author manuscript; available in PMC: 2020 Dec 1.
Published in final edited form as: Otolaryngol Head Neck Surg. 2019 Oct 1;161(6):1004–1011. doi: 10.1177/0194599819877649

Establishing an Animal Model of Single-Sided Deafness in Chinchilla lanigera

Renee M Banakis Hartl 1, Nathaniel T Greene 1, Victor Benichoux 2, Anna Dondzillo 1, Andrew D Brown 3, Daniel J Tollin 1,3
PMCID: PMC6917427  NIHMSID: NIHMS1062034  PMID: 31570054

Abstract

Objectives:

  1. Characterize changes in brainstem neural activity following unilateral deafening in an animal model.

  2. Compare brainstem neural activity from unilaterally-deafened animals to that of normal-hearing controls.

Study Design:

Prospective, controlled animal study.

Setting:

Vivarium and animal research facilities.

Subjects and Methods:

The effect of single-sided deafness (SSD) on brainstem activity was studied in Chinchilla lanigera. Animals were unilaterally deafened via gentamycin injection into the middle ear, which was verified by loss of auditory brainstem responses (ABR). Animals underwent measurement of ABR and local field potential (LFP) in the inferior colliculus (IC).

Results:

Four animals underwent chemical deafening, with two normal-hearing animals as controls. ABRs confirmed unilateral loss of auditory function. Deafened animals demonstrated symmetric LFP responses that were distinctly different than the contralaterally-dominated responses of the IC seen in normal-hearing animals.

Conclusion:

We successfully developed a model for unilateral deafness to investigate effects of SSD on brainstem plasticity. This preliminary investigation serves as a foundation for more comprehensive studies that will include cochlear implantation and manipulation of binaural cues, as well as functional behavioral tests.

Introduction:

Single-sided deafness (SSD), defined as severe to profound hearing loss in one but not the other ear, and with a substantial asymmetry in thresholds across ears, is a common clinical problem that presents a challenge for clinicians to manage. Patients who suffer from SSD have poor audibility, and therefore poor speech discrimination abilities in the affected ear, even after loss of hearing sensitivity has been compensated with amplification, thus are poor candidates for traditional hearing aids. Aural rehabilitation for these individuals tends to focus primarily on redirecting sound to the normal hearing ear with CROS (contralateral routing of acoustic signal) hearing aids or bone-anchored hearing implants. Although these technologies have been able to provide sound awareness for these patients on the deaf side, lack of true binaural input limits speech understanding in background noise and sound localization abilities1,2.

Though not FDA-approved at this time, cochlear implantation (CI) has emerged as a potential option for management of SSD. Several studies suggest that patients who have been implanted for SSD show improvement in speech understanding in background noise3–6; however data conflict regarding the listening conditions in which such benefits are realized7, and no testing condition has consistently demonstrated benefit for understanding speech in background noise with CI for SSD. Cochlear implantation for SSD has also been hypothesized to improve sound-source localization abilities, though conclusions in the current literature are mixed4,8,9. Despite these initially promising studies, there remains high variability in objective outcomes with CI for SSD and the reasons for this variability are not well understood. Lack of knowledge regarding the source of the limitations of CI for SSD hamper the development of this potentially important intervention strategy.

Most studies report subjectively better speech understanding in noise and quiet, improved localization, and reduction of tinnitus perception after CI, suggesting substantial improvements of patient quality of life; however, studies with large cohorts, good controls, and objective measures of speech performance in noise and localization are lacking. Given the small population available for clinical study, SSD subjects with CIs are often treated as a single cohort despite widely different hearing losses of diverse etiology, age of onset, duration, and history with amplification – variables that are known to affect outcomes of implantation. In this context, determining the potential benefits of implantation for SSD in patients remains challenging. Furthermore, without FDA approval, CI for SSD will continue to be restricted, and clinical research in the United States will remain limited.

To fill this gap, we have developed an animal model with a pharmacologically-induced SSD. This enables us to utilize electrophysiologic measures to test objective changes in binaural function in the auditory brainstem and midbrain. The use of an animal model provides control over variables such as age of onset, cause, and duration of deafness. Here, we establish an animal model to investigate electrophysiological changes before and after unilateral deafening in order to better understand the effects of the duration of SSD on brainstem plasticity, which could explain the highly variable performance outcomes observed in clinical populations. We hypothesize that unilateral deafening will lead to loss of contralateral response dominance at the level of the inferior colliculus, leading to a loss of the differential brainstem input requisite for binaural hearing (see Figure 1).

Figure 1:

Figure 1:

Open in a new tab

Animals undergo unilateral chemical ablation of the cochlea (A). Normal hearing animals demonstrate contralateral dominance in IC activity (B), acute deafening produces more symmetric activation (C), and cochlear implantation restores contralateral dominance (D).

Methods:

Animals:

Procedures were reviewed and approved by the University of Colorado Denver Animal Care and Use Committees (Protocol #B-73515(11)1D). Our laboratory has developed an animal model for SSD in Chinchilla lanigera10–12, a species that is audiometrically comparable to humans13,14 with large, easily surgically accessible ears15–17, auditory precociousness18, and ability to use interaural timing and level difference cues19. General anesthesia was induced in 6 adult female chinchillas with an intramuscular injection of ketamine hydrochloride (KetaVed, 30 mg/kg) and xylazine hydrochloride (TranquiVed, 5 mg/kg); supplementary injections were administered to maintain an adequate level of anesthesia. Core body temperature was monitored and maintained with a heating pad at 37°C. Animals were divided into two groups: 4 underwent a unilateral deafening procedure and 2 were used for controls.

Deafening Procedure:

After verification of normal hearing in both ears via auditory brainstem response (ABR) testing, 4 chinchillas underwent a transbulla injection of 1.0 cc of gentamicin (40 mg/mL). Two additional animals were left untreated for control. Previous investigation has demonstrated significant loss of both inner and outer hair cells, as well as absent otoacoustic emissions and ABR after a single instillation of gentamicin into the middle ear space of chinchillas20. We observed loss of ipsilaterally-evoked ABR with preserved contralaterally-evoked thresholds within 24 hours of transbulla gentamicin instillation, and changes noted in hearing thresholds after chemical deafening were verified to be stable on repeat testing for up to five days without observable change in the untreated ear (Figure 2A). A hair bundle labeling of Phalloidin and a hair cell specific marker myosin7a were used to stain cochlear preparations from an animal that underwent unilateral deafening. These demonstrated hair cell loss in the deafened ear and preserved cochlear morphology on the untreated side (Figure 2B and 2C).

Figure 2:

Figure 2:

Open in a new tab

Chemical deafening increases ipsilateral ABR thresholds (A), and staining with Phalloidin and myosin 7a confirms hair cell architecture preservation in an untreated ear (B) and changes in hair cell morphology in the deafened ear (C).

Physiologic Assessment:

Physiologic assessment for all animals included both auditory brainstem response testing and measurement of inferior colliculus activity completed on the day of data collection. The four animals that underwent chemical deafening were tested within 5–7 days following the acute procedure, and all were verified to have a complete loss of ABR ipsilateral to treatment prior to initiating IC measurements.

Auditory brainstem response (ABR).

Electrophysiologic recordings were made using methods detailed in prior publications21,22. Briefly, anesthetized animals were positioned in a custom stereotaxic head holder. Tight-fitting earpieces were fitted into the external auditory meati to facilitate the presentation of acoustic stimuli. In order to equalize the sound spectrum at the ear canal entrance, the impulse response of the system was measured with a logarithmic chirp (200 Hz to 24 kHz at 1 octave per second) using Etymotic ER-7C probe microphones. Amplitude and phase calibration filters were generated from the impulse responses22. Acoustic clicks were presented both binaurally and monaurally to each ear individually, with intensities ranging from 20 to 110 dB SPL. Needle electrodes were placed subcutaneously along the midline at vertex and occiput with a grounding electrode placed in the hind leg muscle. All recordings were completed in a double-walled, sound-attenuating booth (Industrial Acoustics, Bronx, NY).

Ensemble neural activity of the interior colliculus (IC).

Extracellular recordings were made within the central nucleus of the IC using methods detailed in prior publications from our lab23,24. Neural activity was recorded at multiple locations in the both the left and right IC using 16-channel silicon probes (NeuroNexus Technologies, 100 or 150 μm linear spacing, 177 μm2 site area). Multielectrode arrays were passed into each IC 4–8 times per experiment. Frequency-vs-intensity response maps (20–90 dB SPL, 10 dB steps; 500 Hz – 8 kHz, 4 steps per octave) were collected on all electrode contacts.

Analysis:

To recover the low-frequency local field potentials (LFP), signals from the electrodes were filtered between 50 and 300 Hz. The reported LFP values correspond to the gain between the root-mean-square (RMS) of the signals when the signal was present (stimulus-driven) and absent (baseline). Significant positive values indicated that the LFP was greater during stimulus presentation, i.e. stimulus driven. Electrophysiological responses were compared between animals that had undergone chemical ablation and animals with normal bilateral hearing.

Results:

Auditory Brainstem Response:

Prior to invasive brainstem recordings, each animal underwent auditory brainstem response testing. Figure 3 illustrates example ABR waveforms from a deafened animal (A and B) and a normal-hearing control (C and D). All animals that had undergone unilateral deafening demonstrated loss of hearing in the treated ear as verified by loss of ABR at equipment output limits (~110 dB SPL). No significant change from baseline hearing in the untreated ear was noted for any test animal. All control animals demonstrated symmetric, normal thresholds as verified by ABR.

Figure 3:

Figure 3:

Open in a new tab

A representative ABR waveforms for a deafened animal demonstrate loss of normal ABR morphology on the deafened side (B) with preserved thresholds in the untreated ear (A). Waveforms recorded from a normal-hearing animal displays symmetric thresholds (C, D).

Ensemble Neuron Activity in the Inferior Colliculus:

Low-frequency local field potential (LFP) amplitude was used to characterize relative activity level in the inferior colliculi of treated versus control animals. In treated animals, since stimulation of the deaf ear was ineffective (as evidenced by ABRs; see Figure 3), data were only obtained with stimulation of the intact ear. In the following, per convention, the “ipsilateral” inferior colliculus is that on the same side (right/left) as the stimulated ear, and “contralateral” is that opposite the stimulated ear. Figure 4 shows frequency-intensity maps for individual animals, with recordings across multiple electrodes (A) and averaged for both hearing (4B and 4C) and unilaterally deafened animals (4E and 4F). Figures 4B, 4C, 4E and 4F demonstrate IC activation after chemical deafening averaged over all electrode channels and overlapping electrode positions in the same penetration. White lines in the figures represent the threshold, defined as the point at which activity is 3 dB above the noise floor. In other words, inferior colliculus neurons responded to sounds with combinations of frequency and intensity above the line and did not respond for stimuli below the line.

Figure 4:

Figure 4:

Open in a new tab

Ensemble neuron activity in the inferior colliculus. Frequency-intensity response maps display low-frequency local field potential (LFP) across the 16 channels of a multielectrode array to ipsilateral and contralateral stimuli for control and deafened animals.

Figure 4D and 4G show these the frequency-specific contralateral thresholds plotted by the ipsilateral thresholds, with the size of the circle corresponding to number of data points. Points resting on the unity line demonstrate symmetric responses, while those falling above or below indicate asymmetric inferior colliculus activity between ipsilateral and contralateral stimuli. Another representation of degree of symmetry between ipsilateral and contralateral stimulation is shown in Figures 4H and 4I, where average IC thresholds for all animals are graphed by frequency, with ipsilaterally-driven responses graphed in blue and contralaterally-driven in green. For control animals, thresholds are lower for contralateral stimulation, while no difference in thresholds can be appreciated for unilaterally-deafened animals.

Discussion:

In this study, we have demonstrated changes in the responses of the auditory midbrain that occur following unilateral deafness. Animals that have undergone chemical deafening via gentamicin injection into the middle ear show loss of hearing as evidenced morphologically by hair cell damage and functionally by loss of ipsilateral auditory brainstem response. These animals also demonstrate notably symmetric neural activation at the level of the inferior colliculus, a deviation from the contralateral dominance evident in normal-hearing animals. Contralateral bias in midbrain activation is likely essential for normal binaural and spatial hearing, as relative activity level across the two hemispheres is central parameter in leading models of sound location encoding25,26. Evidence that SSD leads to abnormally symmetric midbrain activity is important as we continue to explore avenues for SSD treatment options; rehabilitation paradigms should be able to demonstrate the potential to recapitulate the normal asymmetric activation at the level of the brainstem in order to provide the input needed to restore access to binaural cues.

Effects of Unilateral Deafening on Neural Activity and Organization:

Results from our study are comparable to several previous investigations of brainstem-level changes with unilateral deprivation. Unilateral cochlear ablation in ferrets and gerbils have resulted in an increase in activity in both single-unit and multiple-unit recordings of the ipsilateral IC to acoustic stimulation of the intact ear27–29. Patch clamp preparations of IC following unilateral deafening showed altered inhibitory synaptic function by different mechanisms and different magnitudes in the ipsilateral and contralateral IC, with changes appearing to be dominated by postsynaptic alterations in the contralateral IC and by presynaptic changes in the ipsilateral IC30.

Cochlear lesions have been also been associated with hyperactivity in the contralateral inferior colliculus, as evidenced by a higher spontaneous firing rate from single units31,32. Altered glucose uptake in the inferior colliculus of gerbils that have undergone unilateral cochlear ablation33 and reduced volume of the ventral cochlear nucleus in rats that have undergone unilateral-deafening during the neonatal period34 provide additional evidence of brainstem plasticity.

Alterations in neural activity have also been characterized by quantifying changes in protein expression following unilateral deafening. Decreased glutamate decarboxylase and GABA receptor expression35,36, as well as decreased expression of potassium channels35, have been observed in both ipsilateral and contralateral IC following unilateral cochlear ablation. These changes confirm plasticity in expression of neurotransmission- and membrane excitability-related genes in the IC in response to the unilateral auditory deprivation that may account for the observed electrophysiologic alterations in activation patterns.

Objective Changes in Neural Activity with Electrical Stimulation:

Electrical stimulation has been investigated as a means of reversing alterations in electrophysiology and gene expression following unilateral deafening. Glycinergic receptor and glutamic acid decarboxylase expression were noted to be reduced in guinea pigs after unilateral cochlear ablation, but the down-regulation could be reversed somewhat by electrical stimulation37. Guinea pigs that have undergone cochlear implantation also demonstrate a reduction in average spontaneous activity in the dorsal cochlear nucleus and the medial geniculate body, which is typically elevated after cochlear injury38.

Cochlear implantation in bilaterally deaf animals also provides evidence of neural plasticity that may provide insight into changes in the unilaterally-deafened population. Chronic electrical stimulation has demonstrated improved survival of spiral ganglion cells39,40, partial reversal of deafening-induced changes in cochlear nucleus cell size and synapse morphology39,40, and higher temporal resolution of single IC neurons40. Though electrical stimulation-mediated reversal of the down-regulative changes in bilateral deafness may not be directly applicable to SSD, it may be expected that similar alterations would occur with electrical stimulation for unilateral deafness.

Evidence for Restoration of Binaural Hearing with Cochlear Implantation:

The potential to restore binaural hearing with cochlear implants for patients with single-sided deafness has been evaluated in humans with a variety of psychophysical investigations aimed at examining performance at speech-in-noise and localization tasks for patients that have undergone implantation. Several individual studies suggest improvement in speech understanding in background noise while using a cochlear implant compared with performance with the only hearing ear when noise is directed to the normal hearing ear and speech is directed to the implanted ear3–6. A meta-analysis conducted by Blasco and Redleaf7 showed improvement in performance with co-located speech and noise at 0° azimuth, but not with speech and noise originating from separate locations as in the previous individual studies. Looking across these studies, no testing condition has consistently demonstrated reproducible benefit of CI for SSD for understanding speech in background noise.

Cochlear implantation for SSD has also been hypothesized to improve sound-source localization. In one study, sound localization performance improved for SSD patients with a unilateral CI when listening bilaterally compared with listening via the normal hearing ear alone4. Another investigation revealed that single-sided deaf patients with unilateral cochlear implants show better localization than bimodal cochlear implant patients, but poorer localization than normal hearing listeners8,9. In one case report, cochlear implantation followed by 3 months of auditory training improved sound localization ability, suggesting the potential benefit of post-implantation auditory rehabilitation41. Despite these initially promising studies, there remains high variability in objective outcomes with cochlear implantation for SSD and the reasons for this variability are not known or understood. Lack of knowledge regarding the source of the limitations of CI application to SSD will limit utilization of this potentially important intervention strategy.

Limitations:

Data presented here inform the understanding of the effects of unilateral deprivation on neural function. Additional development of this new animal model will improve prospects for understanding and managing maladaptive plasticity in SSD patients, particularly those considering treatment such as cochlear implantation. While an animal model does allow for invasive measures of neural function not possible in humans and Chinchilla lanigera was selected for its audiometric similarity to humans, observations are not expected to uniformly translate to humans. Additionally, while behavioral studies are possible in this animal model such that observed physiologic changes may be related to behavioral outcomes19, reduced animal behavioral tasks may yield limited insight on the complex tasks and stimuli encountered by human listeners, such as speech perception in noise.

An important consideration when interpreting results of studies inducing unilateral hearing loss with a pharmacological intervention is the degree of segregation between the two ears. Prior studies have shown transmission of gentamycin to the contralateral ear in chinchillas. Three transmission routes were proposed: the Eustachian tubes, which are continuously open in chinchillas42, systemic transmission, and the cochlear aqueduct, which is widely patent in chinchillas43 and guinea pigs44. The first two routes appear unlikely in an anesthetized model; however, the third may provide a pathway for the drug to travel to the contralateral ear. Results may therefore include the effects of a partial hearing loss bilaterally and may explain the increased ABR thresholds observed within 24 hours of deafening (Figure 2A), and somewhat elevated thresholds observed at mid frequencies in contralateral LFPs (i.e. Figure 5D) in the results from unilaterally deafened chinchillas presented here. Future studies involving unilateral chemical deafening will need to account for such transmission in the experimental plan and interpretation of their results.

Figure 5:

Figure 5:

Open in a new tab

Average LFPs, for ipsilateral and contralateral stimuli, for control (A-B) and deafened (C-D) animals. Contralateral vs ipsilateral thresholds (E), and average threshold across frequency (F), reveal asymmetric [symmetric] responses in control (blue) [deafened (red)] animals. Shaded areas above and below illustrate the standard deviation of the average thresholds.

Future Directions:

The results obtained from this model provides an important foundation for future work investigating the treatment of single-sided deafness with cochlear implants. Moving forward, we plan to make similar measurements of activity in the inferior colliculus with both acoustic and electrical stimulation in order to observe whether contralateral dominance can be restored. Though similar results have been presented in other species27–29, the model presented here is uniquely beneficial due to the animal chosen. The audiogram of Chinchilla lanigera overlaps best with humans when compared with other rodent species13,14, and, like humans, they demonstrate auditory precociousness18. Additionally, the chinchilla —with known access to binaural time and level cues19—lends itself to behavioral assays that may be used to evaluate auditory function following cochlear implantation.

Conclusions:

We have developed a new animal model for SSD and have demonstrated changes in auditory midbrain activity via electrophysiological measures. Whereas normal-hearing chinchillas demonstrate contralaterally dominant neural activity in the inferior colliculus, animals that have undergone chemical deafening show symmetric inferior colliculus activation. Loss of contralateral bias in auditory midbrain sensitivity is predicted to result in a reduced capacity for binaural hearing. Future experimentation will examine the ability of electrical stimulation to restore normal activation patterns in the auditory brainstem, with the overarching aim of optimizing cochlear implants in rehabilitating binaural hearing for unilateral deafness.

SSD will continue to present a challenge to clinicians given the fundamental difficulty in providing effective stimulation to the deafened ear. As we move forward in exploring cochlear implantation as an option for these patients, animal models like the one presented here will serve an essential role in evaluating means to best restore normal patterns of neural activation and reestablish binaural hearing function lost during the period of unilateral deprivation.

Funding:

Research supported by the University of Colorado Denver T-32 Institutional Training Grant in Otolaryngology Research: 5T32DC012280-03, by an AAO-HNSF Resident Research Grant, and by a Hearing Health Foundation Emerging Research Grant

Footnotes

Conflict of Interest Statement: No potential conflict of interest was reported by the authors.

References:

  • 1.Gordon K, Henkin Y, Kral A. Asymmetric Hearing During Development: The Aural Preference Syndrome and Treatment Options. Pediatrics. 2015;136(1):141–153. [DOI] [PubMed] [Google Scholar]
  • 2.Moore DR. Anatomy and physiology of binaural hearing. Audiology. 1991;30(3):125–134. [DOI] [PubMed] [Google Scholar]
  • 3.Buechner A, Brendel M, Lesinski-Schiedat A, et al. Cochlear implantation in unilateral deaf subjects associated with ipsilateral tinnitus. Otol Neurotol. 2010;31(9):1381–1385. [DOI] [PubMed] [Google Scholar]
  • 4.Firszt JB, Holden LK, Reeder RM, Waltzman SB, Arndt S. Auditory abilities after cochlear implantation in adults with unilateral deafness: a pilot study. Otol Neurotol. 2012;33(8):1339–1346.. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 5.Hassepass F, Aschendorff A, Wesarg T, et al. Unilateral deafness in children: audiologic and subjective assessment of hearing ability after cochlear implantation. Otol Neurotol. 2013;34(1):53–60. [DOI] [PubMed] [Google Scholar]
  • 6.Vlastarakos PV, Nazos K, Tavoulari E-F, Nikolopoulos TP. Cochlear implantation for single-sided deafness: the outcomes. An evidence-based approach. Eur Arch Otorhinolaryngol. 2014;271(8):2119–2126. [DOI] [PubMed] [Google Scholar]
  • 7.Blasco MA, Redleaf MI. Cochlear implantation in unilateral sudden deafness improves tinnitus and speech comprehension: meta-analysis and systematic review. Otol Neurotol. 2014;35(8):1426–1432. [DOI] [PubMed] [Google Scholar]
  • 8.Dorman MF, Zeitler D, Cook SJ, et al. Interaural level difference cues determine sound source localization by single-sided deaf patients fit with a cochlear implant. Audiol Neurootol. 2015;20(3):183–188. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Zeitler DM, Dorman MF, Natale SJ, Loiselle L, Yost WA, Gifford RH. Sound Source Localization and Speech Understanding in Complex Listening Environments by Single-sided Deaf Listeners After Cochlear Implantation. Otol Neurotol. 2015;36(9):1467–1471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Koka K, Holland NJ, Lupo JE, Jenkins HA, Tollin DJ. Electrocochleographic and mechanical assessment of round window stimulation with an active middle ear prosthesis. Hear Res. 2010;263(1–2):128–137. [DOI] [PubMed] [Google Scholar]
  • 11.Thornton JL, Chevallier KM, Koka K, Gabbard SA, Tollin DJ, Tollin D. Conductive hearing loss induced by experimental middle-ear effusion in a chinchilla model reveals impaired tympanic membrane-coupled ossicular chain movement. J Assoc Res Otolaryngol. 2013;14(4):451–464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 12.Tringali S, Koka K, Jenkins HA, Tollin DJ. Sound location modulation of electrocochleographic responses in chinchilla with single-sided deafness and fitted with an osseointegrated bone-conducting hearing prosthesis. Otol Neurotol. 2015;36(4):678–686. [DOI] [PubMed] [Google Scholar]
  • 13.Heffner RS, Heffner HE. Behavioral hearing range of the chinchilla. Hear Res. 1991;52(1):13–16. [DOI] [PubMed] [Google Scholar]
  • 14.Miller JD. Audibility curve of the chinchilla. J Acoust Soc Am. 1970;48(2):513–523. [DOI] [PubMed] [Google Scholar]
  • 15.Koka K, Jones HG, Thornton JL, Lupo JE, Tollin DJ. Sound pressure transformations by the head and pinnae of the adult Chinchilla (Chinchilla lanigera). Hear Res. 2011;272(1–2):135–147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Vrettakos PA, Dear SP, Saunders JC. Middle ear structure in the chinchilla: a quantitative study. Am J Otolaryngol. 1988;9(2):58–67. [DOI] [PubMed] [Google Scholar]
  • 17.Browning GC, Granich MS. Surgical anatomy of the temporal bone in the chinchilla. Ann Otol Rhinol Laryngol. 1978;87(6 Pt 1):875–882. [DOI] [PubMed] [Google Scholar]
  • 18.Jones HG, Koka K, Tollin DJ. Postnatal development of cochlear microphonic and compound action potentials in a precocious species, Chinchilla lanigera. J Acoust Soc Am. 2011;130(1):EL38–EL43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Heffner RS, Heffner HE, Kearns D, Vogel J, Koay G. Sound localization in chinchillas. I: Left/right discriminations. Hear Res. 1994;80(2):247–257. [DOI] [PubMed] [Google Scholar]
  • 20.Hilton M, Chen J, Kakigi A, Hirakawa H, Mount RJ, Harrison RV. Middle ear instillation of gentamicin and streptomycin in chinchillas: electrophysiological appraisal of selective ototoxicity. Clin Otolaryngol Allied Sci. 2002;27(6):529–535. [DOI] [PubMed] [Google Scholar]
  • 21.Ferber AT, Benichoux V, Tollin DJ. Test-Retest Reliability of the Binaural Interaction Component of the Auditory Brainstem Response. Ear Hear. 2016;37(5):e291–e301. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Beutelmann R, Laumen G, Tollin D, Klump GM. Amplitude and phase equalization of stimuli for click evoked auditory brainstem responses. J Acoust Soc Am. 2015;137(1):EL71–EL77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Benichoux V, Brown AD, Anbuhl KL, Tollin DJ. Representation of Multidimensional Stimuli: Quantifying the Most Informative Stimulus Dimension from Neural Responses. J Neurosci. 2017;37(31):7332–7346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Jones HG, Brown AD, Koka K, Thornton JL, Tollin DJ. Sound frequency-invariant neural coding of a frequency-dependent cue to sound source location. J Neurophysiol. 2015;114(1):531–539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 25.Grothe B, Pecka M, McAlpine D. Mechanisms of sound localization in mammals. Physiol Rev. 2010;90(3):983–1012. [DOI] [PubMed] [Google Scholar]
  • 26.Stecker GC, Harrington IA, Middlebrooks JC. Location coding by opponent neural populations in the auditory cortex. PLoS Biol. 2005;3(3):e78. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Mossop JE, Wilson MJ, Caspary DM, Moore DR. Down-regulation of inhibition following unilateral deafening. Hear Res. 2000;147(1–2):183–187. [DOI] [PubMed] [Google Scholar]
  • 28.McAlpine D, Martin RL, Mossop JE, Moore DR. Response properties of neurons in the inferior colliculus of the monaurally deafened ferret to acoustic stimulation of the intact ear. J Neurophysiol. 1997;78(2):767–779. [DOI] [PubMed] [Google Scholar]
  • 29.Kitzes LM, Semple MN. Single-unit responses in the inferior colliculus: effects of neonatal unilateral cochlear ablation. J Neurophysiol. 1985;53(6):1483–1500. [DOI] [PubMed] [Google Scholar]
  • 30.Vale C, Juiz JM, Moore DR, Sanes DH. Unilateral cochlear ablation produces greater loss of inhibition in the contralateral inferior colliculus. Eur J Neurosci. 2004;20(8):2133–2140. [DOI] [PubMed] [Google Scholar]
  • 31.Mulders WHAM, Robertson D. Development of hyperactivity after acoustic trauma in the guinea pig inferior colliculus. Hear Res. 2013;298:104–108. [DOI] [PubMed] [Google Scholar]
  • 32.Wang J, Ding D, Salvi RJ. Functional reorganization in chinchilla inferior colliculus associated with chronic and acute cochlear damage. Hear Res. 2002;168(1–2):238–249. [DOI] [PubMed] [Google Scholar]
  • 33.Hutson KA, Durham D, Imig T, Tucci DL. Consequences of unilateral hearing loss: cortical adjustment to unilateral deprivation. Hear Res. 2008;237(1–2):19–31. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Jakob TF, Rosskothen-Kuhl N, Illing R-B. Induction of single-sided deafness in the newborn rat and its consequence for cochlear nucleus volume development. Hear Res. 2016;333:210–215. [DOI] [PubMed] [Google Scholar]
  • 35.Dong S, Mulders WHAM, Rodger J, Robertson D. Changes in neuronal activity and gene expression in guinea-pig auditory brainstem after unilateral partial hearing loss. Neuroscience. 2009;159(3):1164–1174. [DOI] [PubMed] [Google Scholar]
  • 36.Argence M, Saez I, Sassu R, Vassias I, Vidal PP, de Waele C. Modulation of inhibitory and excitatory synaptic transmission in rat inferior colliculus after unilateral cochleectomy: an in situ and immunofluorescence study. Neuroscience. 2006;141(3):1193–1207. [DOI] [PubMed] [Google Scholar]
  • 37.Argence M, Vassias I, Kerhuel L, Vidal P-P, de Waele C. Stimulation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus. Eur J Neurosci. 2008;28(8):1589–1602. [DOI] [PubMed] [Google Scholar]
  • 38.Basta D, Götze R, Gröschel M, et al. Bilateral Changes of Spontaneous Activity Within the Central Auditory Pathway Upon Chronic Unilateral Intracochlear Electrical Stimulation. Otol Neurotol. 2015;36(10):1759–1765. [DOI] [PubMed] [Google Scholar]
  • 39.Miller AL. Effects of chronic stimulation on auditory nerve survival in ototoxically deafened animals. Hear Res. 2001;151(1–2):1–14. [DOI] [PubMed] [Google Scholar]
  • 40.Hardie NA. The consequences of deafness and chronic intracochlear electrical stimulation on the central auditory pathways. Clin Exp Pharmacol Physiol. 1998;25(5):303–309. [DOI] [PubMed] [Google Scholar]
  • 41.Nawaz S, McNeill C, Greenberg SL. Improving sound localization after cochlear implantation and auditory training for the management of single-sided deafness. Otol Neurotol. 2014;35(2):271–276. [DOI] [PubMed] [Google Scholar]
  • 42.Doyle WJ. Eustachian Tube Function in the Chinchilla. Arch Otolaryngol. 1985;111(5):305–308. [DOI] [PubMed] [Google Scholar]
  • 43.Roehm P, Hoffer M, Balaban CD. Gentamicin uptake in the chinchilla inner ear. Hear Res. 2007;230(1–2):43–52. [DOI] [PubMed] [Google Scholar]
  • 44.Ghiz AF, Salt AN, DeMott JE, Henson MM, Henson OW, Gewalt SL. Quantitative anatomy of the round window and cochlear aqueduct in guinea pigs. Hear Res. 2001;162(1–2):105–112. [DOI] [PubMed] [Google Scholar]

RESOURCES