Center for Hearing and Deafness, State University of New York at Buffalo, 137 Cary Hall, 3435 Main Street, Buffalo, NY 14214, USA.
Neuroscience. 2011 Oct 27;194:309-25. doi: 10.1016/j.neuroscience.2011.07.056. Epub 2011 Jul 28.
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.
人们认为，听觉通路中的异常、病变诱导的神经可塑性变化导致了耳鸣的幻音。噪声引起的耳蜗损伤可诱导耳蜗核内广泛的纤维生长和突触形成，但目前尚不清楚这些变化是否与耳鸣有关。为了解决这个问题，我们将 9 只大鼠单侧暴露于中心频率为 12 kHz、声压级为 126 dB 的窄带噪声中 2 小时，然后在 10 周后处死它们，以评估耳蜗核中的突触可塑性（生长相关蛋白 43 [GAP-43]表达）。噪声暴露大鼠和 3 只年龄匹配的对照大鼠在噪声暴露前、暴露后 1-10 天以及暴露后 8-10 周进行了耳鸣样行为筛查，即声刺激的缝隙前抑制（GPIAS）。9 只噪声暴露大鼠中，有 8 只暴露侧的听觉神经纤维 GAP-43 表达上调明显，耳蜗腹核（VCN）明显缩小，而内侧 VCN 的 GAP-43 表达上调强烈，但外侧 VCN 或背侧耳蜗核则无。噪声-无耳鸣大鼠的 VCN 中 GAP-43 的上调明显大于噪声-耳鸣大鼠。1 只噪声-无耳鸣大鼠的听觉神经纤维中 GAP-43 无上调，只有少量的 VCN 缩小，表明听觉神经退化在耳鸣发生中起作用。我们的结果表明，内侧 VCN 中 GAP-43 的强烈上调抑制了噪声诱导的耳鸣。GAP-43 的上调很可能源自内侧橄榄耳蜗神经元。它们对 VCN 抑制性神经元兴奋性输入的增加可能会降低中枢过度兴奋和耳鸣。
