Intense sound-induced plasticity in the dorsal cochlear nucleus of rats: Evidence for cholinergic receptor upregulation

Kaltenbach, James A.; Zhang, Jinsheng

doi:10.1016/j.heares.2006.07.001

Cited by 59 publications

(49 citation statements)

References 55 publications

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“…M currents are strongly inhibited by activation of muscarinic acetylcholine receptors (mAChRs) and other G protein-coupled receptors that reduce membrane phosphatidylinositol-(4,5)-bisphosphate (PIP 2 ) levels (41)(42)(43). Given the important role of cholinergic activity in DCN synaptic plasticity (44) and that noise exposure increases cholinergic activity in the DCN (45,46), our results suggest that noiseinduced up-regulation of mAChR signaling may underlie the reduced KCNQ channel activity in tinnitus mice.…”

Section: Plasticity Of Kcnq2/3 Channels Is Crucial For the Induction mentioning

confidence: 85%

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

Choi

Tzounopoulos

2013

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

130

163

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Tinnitus, the perception of phantom sound, is often a debilitating condition that affects many millions of people. Little is known, however, about the molecules that participate in the induction of tinnitus. In brain slices containing the dorsal cochlear nucleus, we reveal a tinnitus-specific increase in the spontaneous firing rate of principal neurons (hyperactivity). This hyperactivity is observed only in noise-exposed mice that develop tinnitus and only in the dorsal cochlear nucleus regions that are sensitive to high frequency sounds. We show that a reduction in Kv7.2/3 channel activity is essential for tinnitus induction and for the tinnitus-specific hyperactivity. This reduction is due to a shift in the voltage dependence of Kv7 channel activation to more positive voltages. Our in vivo studies demonstrate that a pharmacological manipulation that shifts the voltage dependence of Kv7 to more negative voltages prevents the development of tinnitus. Together, our studies provide an important link between the biophysical properties of the Kv7 channel and the generation of tinnitus. Moreover, our findings point to previously unknown biological targets for designing therapeutic drugs that may prevent the development of tinnitus in humans.potassium channels | excitability | auditory brainstem | phantom perception T innitus is a common auditory disorder that is often the result of extreme sound exposure. An estimated 5-15% of the population experiences chronic tinnitus, with many millions of those sufferers disabled by this condition (1-3). With an even higher prevalence of chronic tinnitus in recent war veterans (4), the personal and financial costs of tinnitus have expanded dramatically. Despite the high prevalence of tinnitus, the neuronal mechanisms that mediate the initiation (induction) and the maintenance (expression) of the disorder remain poorly understood. As a result there is no generally accepted treatment, cure, or preventive method for tinnitus.Tinnitus is usually initiated by noise-induced cochlear damage that causes hair cell loss, ganglion cell degeneration, and reduced auditory nerve input to the central auditory system (5). Decreased peripheral input leads to pathogenic neuronal plasticity that results in subcortical hyperexcitability, increased neural synchrony, cortical reorganization, and ultimately stimulusindependent perception of sound (5-13). However, little is known about the plasticity mechanisms that initiate tinnitus. Elucidation of these mechanisms will lead to the development of drugs and therapies that can be applied soon after the acoustic trauma, thus preventing tinnitus from becoming permanent and irreversible.The dorsal cochlear nucleus (DCN) is an auditory brainstem nucleus that is indispensable to the induction of tinnitus: ablation of the DCN before noise exposure prevents the induction of tinnitus (14). Consistent with its key role in tinnitus generation, the DCN is a site where robust tinnitus-related neuronal plasticity has been identified (15). Studies in animal models of ...

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Section: Plasticity Of Kcnq2/3 Channels Is Crucial For the Induction mentioning

confidence: 85%

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

Choi

Tzounopoulos

2013

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

130

163

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“…Indeed, after an acoustic trauma or an ototoxic intoxication, the central nervous system can increase the spontaneous firing rate of neurons in the dorsal cochlear nucleus 160,161 or decrease gabanergic inhibition in the inferior colliculus. 162,163 This neural hyperactivity maintains a suitable level of excitability of the auditory nerve cells: the phenomena are called "up-regulation" in the dorsal cochlear nucleus and "down-regulation" in the inferior colliculus.…”

Section: Chemical Intoxication and Presbycusismentioning

confidence: 99%

Chemical exposure and hearing loss

Campo¹,

Morata²,

Hong³

2013

Disease-a-Month

125

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“…For example, the decline in glutamatergic input, presumably from primary afferents following noise exposure, is eventually followed by increases in glutamatergic neurotransmission in the cochlear nucleus, superior olivary complex, and IC (Potashner et al 1997;Shore 2011;Zeng et al 2009Zeng et al , 2011. There is also evidence for an upregulation of cholinergic inputs to the cochlear nucleus following noise exposure and cochlear ablation (Chang et al 2002;Jin and Godfrey 2006;Jin et al 2006;Kaltenbach and Zhang 2006). It is widely hypothesized that these changes in the balance of excitation and inhibition within each structure are largely responsible for the induced increases in spontaneous activity that follow in the wake of noise exposure and cochlear injury.…”

mentioning

confidence: 99%

Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

Manzoor

Licari

Klapchar

et al. 2012

Journal of Neurophysiology

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Manzoor NF, Licari F, Klapchar M, Elkin RL, Gao Y, Chen G, Kaltenbach JA. Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus. J Neurophysiol 108: 976 -988, 2012. First published May 2, 2012; doi:10.1152/jn.00833.2011.-Intense noise exposure causes hyperactivity to develop in the mammalian dorsal cochlear nucleus (DCN) and inferior colliculus (IC). It has not yet been established whether the IC hyperactivity is driven by hyperactivity from extrinsic sources that include the DCN or instead is maintained independently of this input. We have investigated the extent to which IC hyperactivity is dependent on input from the contralateral DCN by comparing recordings of spontaneous activity in the IC of noise-exposed and control hamsters before and after ablation of the contralateral DCN. One group of animals was binaurally exposed to intense sound (10 kHz, 115 dB SPL, 4 h), whereas the control group was not. Both groups were studied electrophysiologically 2-3 wk later by first mapping spontaneous activity along the tonotopic axis of the IC to confirm induction of hyperactivity. Spontaneous activity was then recorded at a hyperactive IC locus over two 30-min periods, one with DCNs intact and the other after ablation of the contralateral DCN. In a subset of animals, activity was again mapped along the tonotopic axis after the time course of the activity was recorded before and after DCN ablation. Following recordings, the brains were fixed, and histological evaluations were performed to assess the extent of DCN ablation. Ablation of the DCN resulted in major reductions of IC hyperactivity. Levels of postablation activity in exposed animals were similar to the levels of activity in the IC of control animals, indicating an almost complete loss of hyperactivity in exposed animals. The results suggest that hyperactivity in the IC is dependent on support from extrinsic sources that include and may even begin with the DCN. This finding does not rule out longer term compensatory or homeostatic adjustments that might restore hyperactivity in the IC over time. noise exposure; tinnitus; spontaneous activity; dorsal cochlear nucleus ablation; tonotopic organization MANIPULATIONS THAT CAUSE TINNITUS in human subjects induce dramatic changes in the spontaneous discharge patterns of neurons in auditory centers of the brain. This has been shown in animal studies using acute tinnitus inducers, such as sodium salicylate and quinine (Chen and Jastreboff 1995; Eggermont and Kenmochi 1998;Manabe et al. 1997;Ochi and Eggermont 1997), as well as inducers of chronic tinnitus, including excessive sound exposures (Brozoski et al. 2002;Kaltenbach and McCaslin 1996;Kaltenbach et al. 2000;Seki and Eggermont 2002) and platin drugs (Bauer et al. 2008;Kaltenbach et al. 2002). These treatments cause auditory centers to develop increased levels of bursting and nonbursting spontaneous activity (hyperactivity) and increased synchrony across the neural populations.Such changes have bee...

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Intense sound-induced plasticity in the dorsal cochlear nucleus of rats: Evidence for cholinergic receptor upregulation

Cited by 59 publications

References 55 publications

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

Pathogenic plasticity of Kv7.2/3 channel activity is essential for the induction of tinnitus

Chemical exposure and hearing loss

Noise-induced hyperactivity in the inferior colliculus: its relationship with hyperactivity in the dorsal cochlear nucleus

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