Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Otol Neurotol. 2020 Apr;41(4):e516-e525. doi: 10.1097/MAO.0000000000002573.
To develop a mouse model for temporary and persistent tinnitus using the gap startle paradigm.
Behavioral animal models for tinnitus are classified into conditioning- and reflex-based types. Gap prepulse inhibition of the acoustic startle (GPIAS) is based on the acoustic startle modification by a silent gap and gap detection deficit caused by tinnitus gap filling.
We used C57BL/6J mice inherently susceptible to hearing loss and potentially predisposed to tinnitus. They were divided into the control, salicylate-induced tinnitus, and noise-induced tinnitus groups. Mice were tested with the auditory brainstem response at four frequencies (8, 16, 24, and 32 kHz) and GPIAS in three carrier conditions, 16 and 24 kHz narrow band noises (NBNs) and broadband noise, at multiple time points before and after treatment. The ratio between the gap startle and no-gap startle amplitudes was analyzed by a repeated measures design. In addition, the number of tinnitus-positive mice meeting a specified criterion was counted.
Salicylate/unilateral noise trauma resulted in temporary/permanent tinnitus evidenced by GPIAS reduction. GPIAS reduction was the most significant at 16 kHz NBN among the three carriers in both tinnitus groups. Control mice also showed good gap detection performance at 16 kHz NBN, which is in the most sensitive hearing range in mice.
The GPIAS test in C57BL/6J mice was very reliable at 16 kHz NBN. This tinnitus model developed in the mouse strain of accelerated hearing loss can be used with two options of temporary and persistent tinnitus.
使用间隙起始范式开发一种用于暂时和持续耳鸣的小鼠模型。
耳鸣的行为动物模型分为条件和反射两种类型。声起始抑制的间隙前脉冲（GPIAS）基于无声间隙对声起始的修饰以及耳鸣间隙填充引起的间隙检测缺陷。
我们使用固有易发生听力损失且可能易患耳鸣的 C57BL/6J 小鼠。它们被分为对照组、水杨酸盐诱导的耳鸣组和噪声诱导的耳鸣组。在治疗前后的多个时间点，使用听觉脑干反应在四个频率（8、16、24 和 32kHz）和 GPIAS 测试小鼠，使用三种载频条件，即 16 和 24kHz 窄带噪声（NBN）和宽带噪声。通过重复测量设计分析间隙起始和无间隙起始幅度之间的比率。此外，计算符合特定标准的耳鸣阳性小鼠的数量。
水杨酸盐/单侧噪声创伤导致 GPIAS 降低，证明了暂时/永久性耳鸣。在两种耳鸣组中，三种载频中，16kHz NBN 的 GPIAS 降低最为显著。对照组小鼠在 16kHz NBN 时也表现出良好的间隙检测性能，这是在小鼠最敏感的听力范围内。
在 C57BL/6J 小鼠中，16kHz NBN 的 GPIAS 测试非常可靠。这种在听力损失加速的小鼠品系中开发的耳鸣模型可用于暂时和持续耳鸣两种选择。
