Noise Overexposure Alters Long-Term Somatosensory-Auditory Processing in the Dorsal Cochlear Nucleus-Possible Basis for Tinnitus-Related Hyperactivity?

Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109, USA.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 02/2012; 32(5):1660-71. DOI: 10.1523/JNEUROSCI.4608-11.2012
Source: PubMed


The dorsal cochlear nucleus (DCN) is the first neural site of bimodal auditory-somatosensory integration. Previous studies have shown that stimulation of somatosensory pathways results in immediate suppression or enhancement of subsequent acoustically evoked discharges. In the unimpaired auditory system suppression predominates. However, damage to the auditory input pathway leads to enhancement of excitatory somatosensory inputs to the cochlear nucleus, changing their effects on DCN neurons (Shore et al., 2008; Zeng et al., 2009). Given the well described connection between the somatosensory system and tinnitus in patients we sought to determine whether plastic changes in long-lasting bimodal somatosensory-auditory processing accompany tinnitus. Here we demonstrate for the first time in vivo long-term effects of somatosensory inputs on acoustically evoked discharges of DCN neurons in guinea pigs. The effects of trigeminal nucleus stimulation are compared between normal-hearing animals and animals overexposed with narrow band noise and behaviorally tested for tinnitus. The noise exposure resulted in a temporary threshold shift in auditory brainstem responses but a persistent increase in spontaneous and sound-evoked DCN unit firing rates and increased steepness of rate-level functions. Rate increases were especially prominent in buildup units. The long-term somatosensory enhancement of sound-evoked responses was strengthened while suppressive effects diminished in noise-exposed animals, especially those that developed tinnitus. Damage to the auditory nerve is postulated to trigger compensatory long-term synaptic plasticity of somatosensory inputs that might be an important underlying mechanism for tinnitus generation.

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Available from: Susan E Shore, Oct 02, 2015
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    • "While inducing stimuli (pure tone, noise band) were somewhat different in these studies, the relationship with the induced tinnitus was not simple. The only consistency was that in almost all cases the induced tinnitus was at higher frequencies (e.g., Longenecker and Galazyuk, 2011; Dehmel et al., 2012; Turner et al., 2012). In addition, it should be noted that also in the gerbil model the situation regarding the spectral content of the tinnitus sensation is less clear in the first phase of tinnitus development when the startle-based detection of tinnitus finds more broadband and unstable pattern of tinnitus (Nowotny et al., 2011). "
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    ABSTRACT: Tinnitus often occurs after exposure to loud noise. This raises the question of whether repeated exposure to noise increases the risk of developing tinnitus. We thus studied tinnitus development after repeated acoustic overstimulation using startle and auditory brainstem-response techniques applied to Mongolian gerbils. Noise with bandwidths ranging from 0.25 up to 0.5 oct were used for repeated acoustic overstimulation. Auditory brainstem response measurements revealed similar threshold shifts in both groups of up to about 30 dB directly after the acoustic overstimulation. We identified an upper limit in threshold values, which was independent of the baseline values before the noise exposure. Several weeks after the acoustic overstimulation, animals with the noise bandwidth of 0.25 oct showed a permanent threshold shift, while animals of the group with the 0.5 oct noise band featured only a temporary threshold shift. We thus conclude that the threshold shift directly after noise exposure cannot be used as an indicator for the upcoming threshold level several weeks later. By using behavioural measurements, we investigated the frequency-dependent development of tinnitus-related changes in both groups and one group with 1 oct noise bandwidth. The number of animals that show tinnitus-related changes was highest in animals that received noise with the bandwidth 0.5 oct. This number was, in contrast to the number of animals in the 0.25 oct bandwidth, not significantly increased after repeated overstimulation. The frequency distribution of tinnitus-related changes ranged from 4 to 20 kHz. In the group with the narrow-band noise (0.25 oct) changes centre at one frequency range from 10 to 12 kHz. In the group with the broader noise band (0.5 oct), however, two peaks at 8-10 kHz and at 16-18 kHz were found, which suggests that different mechanisms underlie the tinnitus development.
    Neuroscience 09/2015; 310. DOI:10.1016/j.neuroscience.2015.09.023 · 3.36 Impact Factor
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    • "Tinnitus , the phantom auditory perception , is correlated with fusiform cell hyperactivity ( Brozoski et al . , 2002 ; Kaltenbach et al . , 2004 ; Roberts et al . , 2010 ; Dehmel et al . , 2012 ; Koehler and Shore , 2013a ; Stefanescu et al . , 2015 ) . In addition , tinnitus changes auditory – somatosensory plasticity : using the same stimulus parameters ( 50 ms PT ) , normal animals showed predominant Hebbian STDP while tinnitus animals showed anti - Hebbian STDP ( Koehler and Shore , 2013a ) . The Koehler and Shore study sug"
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    ABSTRACT: The cochlear nucleus (CN) is the first site of multisensory integration in the ascending auditory pathway. The principal output neurons of the dorsal cochlear nucleus (DCN), fusiform cells, receive somatosensory information relayed by the CN granule cells from the trigeminal and dorsal column pathways. Integration of somatosensory and auditory inputs results in long-term enhancement or suppression in a stimulus-timing-dependent manner. Here, we demonstrate that stimulus-timing-dependent plasticity (STDP) can be induced in DCN fusiform cells using paired auditory and transcutaneous electrical stimulation of the face and neck to activate trigeminal and dorsal column pathways to the CN, respectively. Long-lasting changes in fusiform cell firing rates persisted for up to 2 h after this bimodal stimulation, and followed Hebbian or anti-Hebbian rules, depending on tone duration, but not somatosensory stimulation location: 50 ms paired tones evoked predominantly Hebbian, while 10 ms paired tones evoked predominantly anti-Hebbian plasticity. The tone-duration-dependent STDP was strongly correlated with first inter-spike intervals, implicating intrinsic cellular properties as determinants of STDP. This study demonstrates that transcutaneous stimulation with precise auditory-somatosensory timing parameters can non-invasively induce fusiform cell long-term modulation, which could be harnessed in the future to moderate tinnitus-related hyperactivity in DCN.
    Frontiers in Systems Neuroscience 08/2015; 9:116. DOI:10.3389/fnsys.2015.00116
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    • "Interestingly, similar to the long-term changes in firing activity of fusiform cells, auditory-Sp5 bimodal stimulation induced persistent changes in the tone and RLF responses of primary-like cells in VCN (Figs. 5A and B) but not in the IC (Figs. 5C and D). The long-term effects correspond to the upregulation of somatosensory innervation in CN (Section 4.3), and likely underlie induction of hyperactivity and tinnitus (Dehmel et al., 2012). Indeed, as IC does not exhibit long-term bimodal plasticity, a probable induction mechanism (Fig. 5D), IC hyperactivity probably cannot occur independently of DCN hyperactivity ( "
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    ABSTRACT: Tinnitus, the phantom perception of sound, is physiologically characterized by an increase in spontaneous neural activity in the central auditory system. However, as tinnitus is often associated with hearing impairment, it is unclear how a decrease of afferent drive can result in central hyperactivity. In this review, we first assess methods for tinnitus induction and objective measures of the tinnitus percept in animal models. From animal studies, we discuss evidence that tinnitus originates in the cochlear nucleus (CN), and hypothesize mechanisms whereby hyperactivity may develop in the CN after peripheral auditory nerve damage. We elaborate how this process is likely mediated by plasticity of auditory-somatosensory integration in the CN: the circuitry in normal circumstances maintains a balance of auditory and somatosensory activities, and loss of auditory inputs alters the balance of auditory somatosensory integration in a stimulus timing dependent manner, which propels the circuit towards hyperactivity. Understanding the mechanisms underlying tinnitus generation is essential for its prevention and treatment. Copyright © 2015. Published by Elsevier B.V.
    Hearing research 06/2015; DOI:10.1016/j.heares.2015.06.005 · 2.97 Impact Factor
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