The gap-startle paradigm for tinnitus screening in animal models: limitations and optimization.

The gap-startle paradigm for tinnitus screening in animal models: limitations and optimization.
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DOI:
10.1016/j.heares.2012.06.001
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发表时间:
2013-01
期刊:
影响因子:
2.8
通讯作者:
Allman, Brian L.
Allman, Brian L.
中科院分区:
医学1区
文献类型:
--
作者:
Lobarinas, Edward;Hayes, Sarah H.;Allman, Brian L.

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In 及其同事(Behav Neurosci,120:188-195)引入了间隙惊吓范式作为大鼠耳鸣筛查的高通量方法。在此范例下,通过确定在大声的惊吓刺激之前插入连续背景声音中的短无声间隙产生的声惊吓反射的抑制水平来评估间隙检测能力。如果包含间隙的背景声音与耳鸣音调在性质上相似,则耳鸣动物预计会表现出间隙检测能力受损(即,缺乏对声惊吓反射的抑制)。因此,为了使间隙惊吓范式成为筛查耳鸣的有效工具,必须存在强有力的惊吓反应来抑制。由于最近的研究表明,噪声暴露后声惊跳反射可能会显着降低,因此我们努力 1)修改间隙惊跳范式,使其在听力损失的情况下更具弹性,2)评估惊跳反应性的减少是否会混淆间隙前脉冲抑制的解释并导致耳鸣筛查错误。在第一个实验中,传统的宽带噪声(BBN)惊吓刺激被带通噪声取代,其中声能集中在较低频率(5-10 kHz),以便在单侧高频噪声暴露(16 kHz)后保持惊吓刺激的可听度。然而,在噪声暴露后,大鼠对带通噪声的惊吓幅度仍然减少了 57%。对另一组患有短暂性传导性听力损失的大鼠进行的后续实验表明,当 BBN 惊吓刺激被大鼠颈后快速吹气所取代时,惊吓反应性得到了更好的保留。此外,研究发现,短暂性单侧传导性听力损失不太可能引起耳鸣,但会导致间隙前脉冲抑制受损(用传统 BBN 间隙惊吓范式评估),导致耳鸣筛查出现假阳性。因此,本研究确定了传统间隙惊吓范式的重要注意事项,并描述了使用吹气惊吓刺激的实验参数,这可能有助于限制噪声暴露后惊吓反应性降低的负面后果,从而使研究人员能够更好地筛查听力损失动物的耳鸣。
In and colleagues (Behav Neurosci, 120:188–195) introduced the gap-startle paradigm as a high-throughput method for tinnitus screening in rats. Under this paradigm, gap detection ability was assessed by determining the level of inhibition of the acoustic startle reflex produced by a short silent gap inserted in an otherwise continuous background sound prior to a loud startling stimulus. Animals with tinnitus were expected to show impaired gap detection ability (i.e., lack of inhibition of the acoustic startle reflex) if the background sound containing the gap was qualitatively similar to the tinnitus pitch. Thus, for the gap-startle paradigm to be a valid tool to screen for tinnitus, a robust startle response from which to inhibit must be present. Because recent studies have demonstrated that the acoustic startle reflex could be dramatically reduced following noise exposure, we endeavored to 1) modify the gap-startle paradigm to be more resilient in the presence of hearing loss, and 2) evaluate whether a reduction in startle reactivity could confound the interpretation of gap prepulse inhibition and lead to errors in screening for tinnitus. In the first experiment, the traditional broadband noise (BBN) startle stimulus was replaced by a bandpass noise in which the sound energy was concentrated in the lower frequencies (5–10 kHz) in order to maintain audibility of the startle stimulus after unilateral high frequency noise exposure (16 kHz). However, rats still showed a 57% reduction in startle amplitude to the bandpass noise post-noise exposure. A follow-up experiment on a separate group of rats with transiently-induced conductive hearing loss revealed that startle reactivity was better preserved when the BBN startle stimulus was replaced by a rapid airpuff to the back of the rats neck. Furthermore, it was found that transient unilateral conductive hearing loss, which was not likely to induce tinnitus, caused an impairment in gap prepulse inhibition as assessed with the traditional BBN gap-startle paradigm, resulting in a false-positive screening for tinnitus. Thus, the present study identifies significant caveats of the traditional gap-startle paradigm, and describes experimental parameters using an airpuff startle stimulus which may help to limit the negative consequences of reduced startle reactivity following noise exposure, thereby allowing researchers to better screen for tinnitus in animals with hearing loss.
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