Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus?

Hickox, Ann E.; Liberman, M. Charles

doi:10.1152/jn.00184.2013

Cited by 291 publications

(293 citation statements)

References 70 publications

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“…Noise-induced cochlear neuropathy can lead to acoustic hypersensitivity (42). Posttraumatic sensitization of damage-resistant type II afferents (7,8), like the peripheral sensitization of somatic nociceptors in hyperalgesia (43), could contribute to the paradoxical "gain of function" of hyperacusis, whereby loud sound becomes acutely painful even when hearing thresholds are elevated.…”

Section: Discussionmentioning

confidence: 99%

Unmyelinated type II afferent neurons report cochlear damage

Liu

Glowatzki

Fuchs

2015

Proc. Natl. Acad. Sci. U.S.A.

114

102

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In the mammalian cochlea, acoustic information is carried to the brain by the predominant (95%) large-diameter, myelinated type I afferents, each of which is postsynaptic to a single inner hair cell. The remaining thin, unmyelinated type II afferents extend hundreds of microns along the cochlear duct to contact many outer hair cells. Despite this extensive arbor, type II afferents are weakly activated by outer hair cell transmitter release and are insensitive to sound. Intriguingly, type II afferents remain intact in damaged regions of the cochlea. Here, we show that type II afferents are activated when outer hair cells are damaged. This response depends on both ionotropic (P2X) and metabotropic (P2Y) purinergic receptors, binding ATP released from nearby supporting cells in response to hair cell damage. Selective activation of P2Y receptors increased type II afferent excitability by the closure of KCNQ-type potassium channels, a potential mechanism for the painful hypersensitivity (that we term "noxacusis" to distinguish from hyperacusis without pain) that can accompany hearing loss. Exposure to the KCNQ channel activator retigabine suppressed the type II fiber's response to hair cell damage. Type II afferents may be the cochlea's nociceptors, prompting avoidance of further damage to the irreparable inner ear.type II cochlear afferents | ATP | acoustic trauma | hyperacusis | noxacusis T he mammalian cochlea is the most elaborate of vertebrate auditory organs. The elegantly coiled, mechanically tuned cochlear duct and functional differentiation between inner hair cells (IHCs) and outer hair cells (OHCs), afferent and efferent neuronal connections are among the features that enable the widest acoustic frequency range and most complex vocalizations among vertebrate species. This benefit, however, has been gained at a significant cost in the metabolic and mechanical vulnerability of cochlear hair cells and neurons. Loud sound progressively damages type I afferent neurons and OHCs (1). Once damaged beyond repair, these do not regenerate as they do in nonmammalian vertebrates, suggesting that protective mechanisms should exist to preserve cochlear function. Indeed, middle ear reflexes (2) and efferent inhibition of hair cells (3) can mitigate acoustic trauma to some extent. However, a more effective strategy is simply to avoid or withdraw from sources of trauma, by analogy to limb withdrawal triggered by C-fiber activation in skin.Here, we provide evidence that unmyelinated type II cochlear afferents can report cochlear trauma, a potential trigger for nocifensive behavior. Hyperactivity of type II neurons could contribute as well to the paradoxical hypersensitivity to loud sound that can accompany hearing loss, despite diminished type I afferent function. Hyperacusis is a comorbidity in 80% of tinnitus patients (4) suggesting common pathogenic mechanisms (5). In the most severe cases, hyperacusis is described as debilitating "ear pain" (6). The response to trauma by type II afferents may relate most directly to such ...

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Section: Discussionmentioning

confidence: 99%

Unmyelinated type II afferent neurons report cochlear damage

Liu

Glowatzki

Fuchs

2015

Proc. Natl. Acad. Sci. U.S.A.

114

102

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“…Tinnitus patients do not show a selective loss of startle inhibition when tested with the GPIAS paradigm (Fournier and Hebert, 2013). Results in laboratory mice are also inconsistent with the assumption that tinnitus fills in the gap (Hickox and Liberman, 2014). For each of these testing procedures, the stimulus differences between tinnitus and the background sound provide a rich source of information for gap detection.…”

Section: Introductionmentioning

confidence: 94%

Improving the Reliability of Tinnitus Screening in Laboratory Animals

Jones

May

2016

JARO

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Behavioral screening remains a contentious issue for animal studies of tinnitus. Most paradigms base a positive tinnitus test on an animal's natural tendency to respond to the Bsound^of tinnitus as if it were an actual sound. As a result, animals with tinnitus are expected to display soundconditioned behaviors when no sound is present or to miss gaps in background sounds because tinnitus Bfills in the gap.^Reliable confirmation of the behavioral indications of tinnitus can be problematic because the reinforcement contingencies of conventional discrimination tasks break down an animal's tendency to group tinnitus with sound. When responses in silence are rewarded, animals respond in silence regardless of their tinnitus status. When responses in silence are punished, animals stop responding. This study introduces stimulus classification as an alternative approach to tinnitus screening. Classification procedures train animals to respond to the common perceptual features that define a group of sounds (e.g., high pitch or narrow bandwidth). Our procedure trains animals to drink when they hear tinnitus and to suppress drinking when they hear other sounds. Animals with tinnitus are revealed by their tendency to drink in the presence of unreinforced probe sounds that share the perceptual features of the tinnitus classification. The advantages of this approach are illustrated by taking laboratory rats through a testing sequence that includes classification training, the experimental induction of tinnitus, and postinduction screening. Behavioral indications of tinnitus are interpreted and then verified by simulating a known tinnitus percept with objective sounds.

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“…GPIASR testing assumes that gap inhibition of the acoustic startle reflex is attenuated in animals with tinnitus because tinnitus "fills the gap." This assumption has been criticized by recent studies showing inconsistent relationships between the gap stimulus and the startle response (Fournier and Hebert 2013;Lobarinas et al 2013;Hickox and Liberman 2014).…”

Section: Introductionmentioning

confidence: 99%

Effects of Unilateral Acoustic Trauma on Tinnitus-Related Spontaneous Activity in the Inferior Colliculus

Ropp

Tiedemann

Young

et al. 2014

JARO

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This study describes the long-term effects of soundinduced cochlear trauma on spontaneous discharge rates in the central nucleus of the inferior colliculus (ICC). As in previous studies, single-unit recordings in Sprague-Dawley rats revealed pervasive increases in spontaneous discharge rates. Based on differences in their sources of input, it was hypothesized that physiologically defined neural populations of the auditory midbrain would reveal the brainstem sources that dictate ICC hyperactivity. Abnormal spontaneous activity was restricted to target neurons of the ventral cochlear nucleus. Nearly identical patterns of hyperactivity were observed in the contralateral and ipsilateral ICC. The elevation in spontaneous activity extended to frequencies well below and above the region of maximum threshold shift. This lack of frequency organization suggests that ICC hyperactivity may be influenced by regions of the brainstem that are not tonotopically organized. Sound-induced hyperactivity is often observed in animals with behavioral signs of tinnitus. Prior to electrophysiological recording, rats were screened for tinnitus by measuring gap pre-pulse inhibition of the acoustic startle reflex (GPIASR). Rats with positive phenotypes did not exhibit unique patterns of ICC hyperactivity. This ambiguity raises concerns regarding animal behavioral models of tinnitus. If our screening procedures were valid, ICC hyperactivity is observed in animals without behavioral indications of the disorder. Alternatively, if the perception of tinnitus is strictly linked to ongoing ICC hyperactivity, our current behavioral approach failed to provide a reliable assessment of tinnitus state.

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Is noise-induced cochlear neuropathy key to the generation of hyperacusis or tinnitus?

Cited by 291 publications

References 70 publications

Unmyelinated type II afferent neurons report cochlear damage

Unmyelinated type II afferent neurons report cochlear damage

Improving the Reliability of Tinnitus Screening in Laboratory Animals

Effects of Unilateral Acoustic Trauma on Tinnitus-Related Spontaneous Activity in the Inferior Colliculus

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