Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization.
Mice Lacking the Alpha9 Subunit of the Nicotinic Acetylcholine Receptor Exhibit Deficits in Frequency Difference Limens and Sound Localization.
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DOI：
10.3389/fncel.2017.00167
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发表时间：
2017
影响因子：
5.3
通讯作者：
Kandler K
中科院分区：
文献类型：
--
作者：
Clause A;Lauer AM;Kandler K
耳蜗中的声音处理由脑干中内侧橄榄耳蜗神经元产生的胆碱能传出轴突调制。这些轴突在发育过程中接触成熟耳蜗中的外毛细胞和内毛细胞，并激活由α9和α10亚基组成的烟碱乙酰胆碱受体。α9亚基对于介导乙酰胆碱对毛细胞的作用是必需的，因为α9亚基的遗传缺失导致耳蜗的功能性胆碱能去传出。听觉起始前耳蜗自发活动的胆碱能调制对于中枢听觉回路的成熟是重要的。在α 9基因敲除小鼠中，外侧上级橄榄的抑制性传入的发育细化受到干扰，导致该声音定位核的音调定位组织减少。在这项研究中，我们使用行为测试来研究α 9 KO小鼠的电路异常是否与声音定位或声音频率处理相关。使用条件性舔抑制任务来测量声音定位，我们发现四分之三的α 9 KO小鼠表现出受损的最小可听角。使用声惊吓反应的前脉冲抑制范例，我们发现α 9 KO小鼠检测声音频率变化的能力受损，而它们检测声音强度变化的能力没有受损。这些结果表明，胆碱能烟碱α9亚单位介导的传输在发育中的耳蜗听力的成熟中起着重要作用。
Sound processing in the cochlea is modulated by cholinergic efferent axons arising from medial olivocochlear neurons in the brainstem. These axons contact outer hair cells in the mature cochlea and inner hair cells during development and activate nicotinic acetylcholine receptors composed of α9 and α10 subunits. The α9 subunit is necessary for mediating the effects of acetylcholine on hair cells as genetic deletion of the α9 subunit results in functional cholinergic de-efferentation of the cochlea. Cholinergic modulation of spontaneous cochlear activity before hearing onset is important for the maturation of central auditory circuits. In α9KO mice, the developmental refinement of inhibitory afferents to the lateral superior olive is disturbed, resulting in decreased tonotopic organization of this sound localization nucleus. In this study, we used behavioral tests to investigate whether the circuit anomalies in α9KO mice correlate with sound localization or sound frequency processing. Using a conditioned lick suppression task to measure sound localization, we found that three out of four α9KO mice showed impaired minimum audible angles. Using a prepulse inhibition of the acoustic startle response paradigm, we found that the ability of α9KO mice to detect sound frequency changes was impaired, whereas their ability to detect sound intensity changes was not. These results demonstrate that cholinergic, nicotinic α9 subunit mediated transmission in the developing cochlear plays an important role in the maturation of hearing.