Article

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

ABSTRACT

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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    • "This cross-modal plasticity in the CN after cochlear damage is of potential importance for 'somatic' tinnitus, in which patients can modify their tinnitus through head and neck maneuvers, such as in jaw clenching (Levine et al., 2003), or when their tinnitus can be attributed to an insult in the head and neck region (Lockwood et al., 1998; Pinchoff et al., 1998, Levine, 1999). Indeed, animals with behaviorally confirmed tinnitus have altered functional auditory–somatosensory integration in the CN (Dehmel et al., 2012; Koehler and Shore, 2013). To further study the role of cochlear damage-induced upregulation of VGLUT2 terminals in the CN in somatic tinnitus, conditional VGLUT2 knock-out studies in mice are of high importance (Brown et al., 2008). "
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    ABSTRACT: Vesicular glutamate transporters 1 and 2 (VGLUT1 and VGLUT2) have distinct distributions in the cochlear nucleus that correspond to the sources of the labeled terminals. VGLUT1 is mainly associated with terminals of auditory nerve fibers, whereas VGLUT2 is mainly associated with glutamatergic terminals deriving from other sources that project to the cochlear nucleus (CN), including somatosensory and vestibular terminals. Previous studies in guinea pig have shown that cochlear damage results in a decrease of VGLUT1-labeled puncta and an increase in VGLUT2-labeled puncta. This indicates cross-modal compensation that is of potential importance in somatic tinnitus. To examine whether this effect is consistent across species and to provide a background for future studies, using transgenesis, the current study examines VGLUT expression profiles upon cochlear insult by intracochlear kanamycin injections in the mouse. Intracochlear kanamycin injections abolished ipsilateral ABR responses in all animals and reduced ipsilateral spiral ganglion neuron densities in animals that were sacrificed after four weeks, but not in animals that were sacrificed after three weeks. In all unilaterally deafened animals, VGLUT1 density was decreased in CN regions that receive auditory nerve fiber terminals, i.e. in the deep layer of the dorsal cochlear nucleus (DCN), in the interstitial region where the auditory nerve enters the CN, and in the magnocellular region of the antero- and posteroventral CN. In contrast, density of VGLUT2 expression was upregulated in the fusiform cell layer of the DCN and in the granule cell lamina, which are known to receive somatosensory and vestibular terminals. These results show that a cochlear insult induces cross-modal compensation in the cochlear nucleus of the mouse, confirming previous findings in guinea pig, and that these changes are not dependent on the occurrence of spiral ganglion neuron degeneration.
    Full-text · Article · Dec 2015 · Neuroscience
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    • "Tinnitus is a subjective perception of a non-existent sound in the form of a constant noise and has several causes, the most prevalent are hearing loss and acoustic trauma (Eggermont and Roberts, 2004). Psychophysical evidence of tinnitus in experimental animals has been associated with hyperactivity of the DCN (Kaltenbach and Afman, 2000; Dehmel et al., 2012; Stolzberg et al., 2012; Li et al., 2013) and bilateral ablation of the DCN in mice prevented the development of tinnitus following acoustic trauma, without influencing already established tinnitus, demonstrating that the DCN is crucial for the development of tinnitus (Brozosky and Bauer, 2005; Brozosky et al., 2012). Indeed, animals with tinnitus induced by acoustic trauma exhibit increased burst firing and spike rate of DCN fusiform neurons (Zhang and Kaltenbach, 1998; Brozosky et al., 2002; Kaltenbach and Zhang, 2007; Li et al., 2013). "
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    ABSTRACT: High doses of salicylate induce reversible tinnitus in experimental animals and humans, and is a common tinnitus model. Salicylate probably acts centrally and induces hyperactivity in specific auditory brainstem areas like the dorsal cochlear nucleus (DCN). However, little is known about the effect of high doses of salicylate in synapses and neurons of the DCN. Here we investigated the effects of salicylate on the excitability and evoked and spontaneous neurotransmission in the main neurons (fusiform, cartwheel and tuberculoventral) and synapses of the DCN using whole cell recordings in slices containing the DCN. For this, we incubate the slices for at least 1 h in solution with 1.4 mM salicylate, and recorded action potentials and evoked and spontaneous synaptic currents in fusiform, cartwheel (CW) and putative tuberculoventral (TBV) neurons. We found that incubation with salicylate did not affect the firing of fusiform and TBV neurons, but decreased the spontaneous firing of cartwheel neurons, without affecting AP threshold or complex spikes. Evoked and spontaneous glutamatergic neurotransmission on the fusiform and CW neurons cells was unaffected by salicylate and evoked glycinergic neurotransmission on fusiform neurons was also unchanged by salicylate. On the other hand spontaneous glycinergic transmission on fusiform neurons was reduced in the presence of salicylate. We conclude that high doses of salicylate produces a decreased inhibitor drive on DCN fusiform neurons by reducing the spontaneous firing of cartwheel neurons, but this effect is not able to increase the excitability of fusiform neurons. So, the mechanisms of salicylate-induced tinnitus are probably more complex than simple changes in the neuronal firing and basal synaptic transmission in the DCN.
    Full-text · Article · Nov 2015 · Hearing research
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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.
    Full-text · Article · Sep 2015 · Neuroscience
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