Relationship between noise-induced hearing-loss, persistent tinnitus and growth-associated protein-43 expression in the rat cochlear nucleus: does synaptic plasticity in ventral cochlear nucleus suppress tinnitus?

doi:10.1016/j.neuroscience.2011.07.056

Neuroscience

Volume 194, 27 October 2011, Pages 309-325

https://doi.org/10.1016/j.neuroscience.2011.07.056 Get rights and content

Abstract

Aberrant, lesion-induced neuroplastic changes in the auditory pathway are believed to give rise to the phantom sound of tinnitus. Noise-induced cochlear damage can induce extensive fiber growth and synaptogenesis in the cochlear nucleus, but it is currently unclear if these changes are linked to tinnitus. To address this issue, we unilaterally exposed nine rats to narrow-band noise centered at 12 kHz at 126 dB sound pressure level (SPL) for 2 h and sacrificed them 10 weeks later for evaluation of synaptic plasticity (growth-associated protein 43 [GAP-43] expression) in the cochlear nucleus. Noise-exposed rats along with three age-matched controls were screened for tinnitus-like behavior with gap prepulse inhibition of the acoustic startle (GPIAS) before, 1–10 days after, and 8–10 weeks after the noise exposure. All nine noise-exposed rats showed similar patterns of severe hair cell loss at high- and mid-frequency regions in the exposed ear. Eight of the nine showed strong up-regulation of GAP-43 in auditory nerve fibers and pronounced shrinkage of the ventral cochlear nucleus (VCN) on the noise-exposed side, and strong up-regulation of GAP-43 in the medial ventral VCN, but not in the lateral VCN or the dorsal cochlear nucleus. GAP-43 up-regulation in VCN was significantly greater in Noise-No-Tinnitus rats than in Noise-Tinnitus rats. One Noise-No-Tinnitus rat showed no up-regulation of GAP-43 in auditory nerve fibers and only little VCN shrinkage, suggesting that auditory nerve degeneration plays a role in tinnitus generation. Our results suggest that noise-induced tinnitus is suppressed by strong up-regulation of GAP-43 in the medial VCN. GAP-43 up-regulation most likely originates from medial olivocochlear neurons. Their increased excitatory input on inhibitory neurons in VCN may possibly reduce central hyperactivity and tinnitus.

Highlights

▶Adult rats were unilaterally exposed to narrow-band noise centered at 12 kHz at 126 dB for 2 h. ▶Noise exposure causes hair cell loss, auditory nerve degeneration, and synaptic growth in the VCN. ▶Noise causes tinnitus in some but not all rats despite same pattern of hair cell loss. ▶No-Tinnitus rats show more GAP-43 expression in VCN than Tinnitus rats 10 weeks after noise. ▶Long-term synaptic plasticity in ventral cochlear nucleus may suppress noise-induced tinnitus.

Section snippets

Animals

Twelve adult male Sprague–Dawley rats (Sasco, Charles River Laboratories International, Inc., Wilmington, MA, USA) were used for this study. Nine experimental rats were unilaterally exposed to high-intensity noise in order to induce tinnitus-like behavior in some rats. Rats were screened for tinnitus before and after the noise exposure using gap prepulse inhibition of acoustic startle (GPIAS) as described below and subsequently separated into two following groups: “Noise-No-Tinnitus” and

Tinnitus screening

All experimental rats and age-matched controls were screened for tinnitus-like behavior with the GPIAS paradigm before noise exposure (“Baseline”), days 1–10 after exposure (“Short-term”), and weeks 8–10 after exposure (“Long term;” Fig. 3). Startle amplitudes at the “no-gap” condition were present in all rats at baseline as well as after noise exposure showing that all rats were capable of a significant startle response. At baseline, all rats showed significant inhibition of startle amplitude

Discussion

Unilateral exposure to narrow-band noise centered at 12 kHz and presented at 126 dB SPL for two h caused nearly complete loss of IHC and OHC in the exposed ear except in the extreme apex. In contrast, little or no hair cell loss was observed in the opposite plugged ear. Ten weeks after exposure, eight rats showed strong expression of GAP-43 in the auditory nerve and medial VCN on the noise-exposed side but not in lateral VCN or in DCN. Up-regulation of GAP-43 in medial VCN was significantly

Acknowledgments

We thank Dr. Paul Allen at the University at Rochester for generously sharing the custom software for startle reflex testing. This project was supported by grant from NIH (R.S., R01 DC009091 and R01DC009219).

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Pain Mechanisms and Sensory NeuroscienceResearch PaperRelationship between noise-induced hearing-loss, persistent tinnitus and growth-associated protein-43 expression in the rat cochlear nucleus: does synaptic plasticity in ventral cochlear nucleus suppress tinnitus?

Abstract

Highlights

Section snippets

Animals

Tinnitus screening

Discussion

Acknowledgments

Neuroscience

Ann Anat

Trends Neurosci

Exp Neurol

Mol Cell Neurosci

Hear Res

Otolaryngol Clin North Am

Trends Neurosci

Braz J Otorhinolaryngol

J Biol Chem

Hear Res

Hear Res

J Psych Res

Otolaryngol Clin North Am

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Neuroscience

Neuroscience

Brain Res Mol Brain Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Hear Res

Neurobiol Dis

Exp Neurol

Neuroscience

Hear Res

Hear Res

Hear Res

Brain Res

Ascending projections to the inferior colliculus

J Comp Neurol

Stimulation by cochlear implant in unilaterally deaf rats reverses the decrease of inhibitory transmission in the inferior colliculus

Eur J Neurosci

Onset neurones in the anteroventral cochlear nucleus project to the dorsal cochlear nucleus

J Assoc Res Otolaryngol

Commissural glycinergic inhibition of bushy and stellate cells in the anteroventral cochlear nucleus

Neuroreport

Tinnitus and neural plasticity of the brain

Otol Neurotol

Primary afferent dendrite degeneration as a cause of tinnitus

J Neurosci Res

Tinnitus and inferior colliculus activity in chinchillas related to three distinct patterns of cochlear trauma

J Neurosci Res

Synaptophysin immunoreactivity in the cochlear nucleus after unilateral cochlear or ossicular removal

Synapse

Synaptic input to cochlear nucleus dendrites that receive medial olivocochlear synapses

J Comp Neurol

Gaze-evoked tinnitus following acoustic neuroma resection: a de-afferentation plasticity phenomenon?

Clin Otolaryngol Allied Sci

Effect of the environment on the dendritic morphology of the rat auditory cortex

Synapse

Pain Mechanisms and Sensory Neuroscience
Research Paper
Relationship between noise-induced hearing-loss, persistent tinnitus and growth-associated protein-43 expression in the rat cochlear nucleus: does synaptic plasticity in ventral cochlear nucleus suppress tinnitus?