A novel effect of cochlear efferents:: In vivo response enhancement does not require α9 cholinergic receptors
A novel effect of cochlear efferents:: In vivo response enhancement does not require α9 cholinergic receptors
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DOI：
10.1152/jn.00067.2007
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发表时间：
2007-05-01
影响因子：
2.5
通讯作者：
Liberman, M. Charles
中科院分区：
文献类型：
--
作者：
Maison, Stephane F.;Vetter, Douglas E.;Liberman, M. Charles
哺乳动物耳蜗外毛细胞接受胆碱能传出神经支配，构成声音诱发负反馈回路的效应臂。传出神经末梢释放乙酰胆碱（ACh）的抑制作用是由α 9/α 10 ACh受体介导的，并且被士的宁有效地阻断。在这里，我们报告了一种新的，传出介导的增强耳蜗声诱发的神经反应和耳声发射小鼠。在对照组中，从传出性休克的70秒时期中观察到的经典抑制效应恢复后，反应幅度缓慢增强至超常水平。电击后增强的幅度可以高达10 dB，并且对于高频声刺激往往更大。全身士的宁在10毫克/公斤消除传出诱导的抑制，揭示了一个纯粹的增强效果的传出休克，峰值传出刺激开始后5秒内，保持恒定的水平，通过刺激时期，并缓慢衰减回基线的时间常数类似于100秒。在α 9乙酰胆碱受体亚基靶向缺失的小鼠中，传出诱发效应类似于士的宁阻断的野生型，进一步表明这种新的传出效应与以前报道的所有胆碱能效应根本不同。
Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by alpha 9/alpha 10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of similar to 100 s. In mice with targeted deletion of the alpha 9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.