声惊吓的间隙检测或间隙前脉冲抑制(GPIAS)已成功用于大鼠和豚鼠耳鸣模型,然而,该系统已被证明在CBA小鼠中具有低功效,具有低基础GPIAS和细微的耳鸣样效应。这里,我们测试了五种小鼠品系(CBA,Balbc,CD-1,C57BL/6和129sv)用于脉冲前抑制(PPI)和间隙检测,具有不同的刺激间隔(ISI),并发现来自CBA遗传背景的小鼠抑制惊吓反应的能力最差存在前脉冲或间隙。CD-1小鼠在所有ISI中表现出不同的反应。有趣的是,C57BL/6,129sv和BalbC显示出预脉冲或具有较短ISI的间隙的有效抑制。谷氨酸天冬氨酸转运体(GLAST)在来自耳蜗的支持细胞中表达并缓冲过量的谷氨酸。我们假设GLAST功能的丧失可能会使耳朵对耳鸣诱导剂敏感,如水杨酸盐。使用更短的ISI获得更大的动态范围来评估耳鸣样效果,我们发现,与野生型(WT)同窝小鼠相比,在GLAST敲除(KO)小鼠中,水杨酸盐对间隙检测的破坏在不同强度的32kHz窄带噪声间隙载波中加剧.进行听性脑干反应(ABR)和失真产物耳声发射(DPOAE)以评估对听力功能的影响。在所有测试频率下,水杨酸盐在GLASTKO小鼠中引起的听觉阈值偏移(接近15dB)大于WT小鼠,尽管DPOAE同样减少。尽管有这些变化,使用宽带隙载波和32kHz预脉冲的抑制不受影响。我们的研究表明,GLAST缺乏可能成为破译药物诱发耳鸣的潜在机制的有用实验模型。在该模型中解决耳鸣的神经学相关性的未来研究可以提供对耳鸣机制的更多见解。
Gap detection or gap pre-pulse inhibition of the acoustic startle (GPIAS) has been successfully used in rat and guinea pig models of tinnitus, yet this system has been proven to have low efficacy in CBA mice, with low basal GPIAS and subtle tinnitus-like effects. Here, we tested five mouse strains (CBA, BalbC, CD-1, C57BL/6 and 129sv) for pre-pulse inhibition (PPI) and gap detection with varying interstimulus intervals (ISI) and found that mice from a CBA genetic background had the poorest capacities of suppressing the startle response in the presence of a pre-pulse or a gap. CD-1 mice displayed variable responses throughout all ISI. Interestingly, C57BL/6, 129sv and BalbC showed efficient suppression with either pre-pulses or gaps with shorter ISI. The glutamate aspartate transporter (GLAST) is expressed in support cells from the cochlea and buffers the excess of glutamate. We hypothesized that loss of GLAST function could sensitize the ear to tinnitus-inducing agents, such as salicylate. Using shorter ISI to obtain a greater dynamic range to assess tinnitus-like effects, we found that disruption of gap detection by salicylate was exacerbated across various intensities of a 32-kHz narrow band noise gap carrier in GLAST knockout (KO) mice when compared to their wild-type (WT) littermates. Auditory brainstem responses (ABR) and distortion-product otoacoustic emission (DPOAE) were performed to evaluate the effects on hearing functions. Salicylate caused greater auditory threshold shifts (near 15 dB) in GLAST KO mice than in WT mice across all tested frequencies, despite similarly reduced DPOAE. Despite these changes, inhibition using broad-band gap carriers and 32 kHz pre-pulses were not affected. Our study suggests that GLAST deficiency could become a useful experimental model to decipher the mechanisms underlying drug-induced tinnitus. Future studies addressing the neurological correlates of tinnitus in this model could provide additional insights into the mechanisms of tinnitus.