Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission
Reflex Modification Audiometry Reveals Dual Roles for Olivocochlear Neurotransmission
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DOI：
10.3389/fncel.2017.00361
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发表时间：
2017-11-22
影响因子：
5.3
通讯作者：
Luebke, Anne E.
中科院分区：
文献类型：
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作者：
Allen, Paul D.;Luebke, Anne E.
大约 15% 的美国成年人表示在嘈杂的环境中存在一定程度的听力困难或存在听觉过滤困难。听觉过滤有客观的临床测试，但对于不依赖于大量训练的小鼠模型的测试却很少。我们使用反射修正听力测定 (RMA) 并制定了小鼠模型的排除标准。这种基于 RMA 的测试利用声学惊吓反应 (ASR) 和预脉冲抑制 ASR 的能力 [即预脉冲抑制 (PPI)] 来评估小鼠检测安静中或嵌入掩蔽噪声中的预脉冲信号的能力。我们研究了四种具有正常耳蜗功能的近交小鼠品系的 PPI 行为，并制定了预测试排除标准和测试/再测试可靠性措施。此外，由于内侧（MOC）和外侧（LOC）橄榄耳蜗传出反馈系统都被认为可以改善听觉行为表现，尤其是在嘈杂的背景下，因此我们检查了缺乏 MOC 受体亚基 a9 烟碱乙酰胆碱受体 [a9 nAChR (-/-)] 或表达过度活跃受体 [a9 nAChR 中 Ld'T 突变的小鼠（及其同窝对照）的 PPI 能力KI]，或仅在 CNS 中缺乏 LOC 传出神经肽、α 降钙素基因相关肽 [aCGRP (-/-)]。由于 CGRP 受体的形成已被证明从幼年到成年会成熟，因此我们还研究了这种成熟是否会反映在幼年和成年 (+/+) 对照以及成年 aCGRP (-/-) 动物的 PPI 行为反应中。我们发现，(-/-) a9 nAChR 动物的安静状态下 50% PPI 反应阈值（50% 正确反应的声级）降低，而受体过度活跃的小鼠 (a9 nAChR KI) 的 50% PPI 反应增加，缺乏 aCGRP (-/-) 的成年小鼠的 50% PPI 反应增加。然而，在背景噪声中，只有缺乏 aCGRP 的小鼠表现出 50% PPI 响应阈值增加，因为 a9 nAChR 成年小鼠系与其同窝对照小鼠之间没有显着差异。这些发现表明，MOC 和 LOC 橄榄耳蜗神经传递协同作用，改善对声音的行为反应。这些实验进一步为其他小鼠模型的快速行为听力评估铺平了道路。
Approximately 15% of American adults report some degree of difficulty hearing in a noisy environment or have auditory filtering difficulties. There are objective clinical tests of auditory filtering, yet few tests exist for mouse models that do not rely on extensive training. We have used reflex modification audiometry (RMA) and developed exclusion criteria for the mouse model. This RMA based test makes use of the acoustic startle response (ASR) and the ability of prepulses to inhibit the ASR [i.e., prepulse inhibition (PPI)] to assess the mouse's ability to detect prepulse signals presented in quiet or embedded in masking noise. We have studied PPI behavior across four inbred mouse strains with normal cochlear function and developed pre-testing exclusion criteria and test/retest reliability measures. Moreover, because both the medial (MOC) and the lateral (LOC) olivocochlear efferent feedback systems have been proposed to improve auditory behavior performance, especially in noisy backgrounds, we have examined PPI abilities in mice (with their littermate controls) either lacking the MOC receptor subunit a9 nicotinic acetylcholine receptor [a9 nAChR (-/-)] or expressing an overactive receptor [Ld'T mutation in a9 nAChR KI], or lacking an LOC efferent neuropeptide, alpha calcitonin gene-related peptide [aCGRP (-/-)] only in the CNS. Because CGRP receptor formation has been shown to mature from juvenile to adult ages, we also studied if this maturation would be reflected in PPI behavioral responses in juvenile and adult (+/+) controls and in adult aCGRP (-/-) animals. We show that 50% PPI response thresholds (sound level with 50% correct responses) in quiet are decreased in the (-/-) a9 nAChR animals, and 50% PPI responses are increased for mice with an overactive receptor (a9 nAChR KI) and are increased in adult mice lacking aCGRP (-/-). However, in background noise, only mice lacking aCGRP exhibited increased 50% PPI response thresholds, as there were no significant differences between a9 nAChR adult mouse lines and their littermate controls. These findings suggest that MOC and LOC olivocochlear neurotransmission work in tandem to improve behavioral responses to sound. These experiments further pave the way for rapid behavioral hearing assessments in other mouse models.