Pauli-Magnus D, Hoch G, Strenzke N, Anderson S, Jentsch T J, Moser T
InnerEarLab, Department of Otolaryngology and Center for Molecular Physiology of the Brain, University of Goettingen, Goettingen, Germany.
Neuroscience. 2007 Nov 9;149(3):673-84. doi: 10.1016/j.neuroscience.2007.08.010. Epub 2007 Aug 10.
Sensorineural hearing loss (SNHL) comprises hearing disorders with diverse pathologies of the inner ear and the auditory nerve. To date, an unambiguous phenotypical characterization of the specific pathologies in an affected individual remains impossible. Here, we evaluated the use of scalp-recorded auditory steady-state responses (ASSR) and transient auditory brainstem responses (ABR) for differentiating the disease mechanisms underlying sensorineural hearing loss in well-characterized mouse models. We first characterized the ASSR evoked by sinusoidally amplitude-modulated tones in wild-type mice. ASSR were robustly elicited within three ranges of modulation frequencies below 200 Hz, from 200 to 600 Hz and beyond 600 Hz in most recordings. Using phase information we estimated the apparent ASSR latency to be about 3 ms, suggesting generation in the auditory brainstem. Auditory thresholds obtained by automated and visual analysis of ASSR recordings were comparable to those found with tone-burst evoked ABR in the same mice. We then recorded ASSR and ABR from mouse mutants bearing defects of either outer hair cell amplification (KCNQ4-knockout) or inner hair cell synaptic transmission (Bassoon-mutant). Both mutants showed an increase of ASSR and ABR thresholds of approximately 40 dB versus wild-type when investigated at 8 weeks of age. Mice with defective amplification displayed a steep rise of ASSR and ABR amplitudes with increasing sound intensity, presumably reflecting a strong recruitment of synchronously activated neural elements beyond threshold. In contrast, the amplitudes of ASSR and ABR responses of mice with impaired synaptic transmission grew very little with sound intensity. In summary, ASSR allow for a rapid, objective and frequency-specific hearing assessment and together with ABR and otoacoustic emissions can contribute to the differential diagnosis of SNHL.
感音神经性听力损失（SNHL）包括内耳和听神经具有多种病理状况的听力障碍。迄今为止，仍无法对受影响个体的特定病理状况进行明确的表型特征描述。在此，我们评估了头皮记录的听觉稳态反应（ASSR）和瞬态听觉脑干反应（ABR）在特征明确的小鼠模型中区分感音神经性听力损失潜在疾病机制的用途。我们首先对野生型小鼠中由正弦调幅音诱发的ASSR进行了特征描述。在大多数记录中，ASSR在低于200 Hz、200至600 Hz以及高于600 Hz的三个调制频率范围内均可被强烈诱发。利用相位信息，我们估计ASSR的表观潜伏期约为3毫秒，提示其产生于听觉脑干。通过对ASSR记录进行自动和视觉分析获得的听觉阈值与同一小鼠中短纯音诱发的ABR所测得的阈值相当。然后，我们从患有外毛细胞放大缺陷（KCNQ4基因敲除）或内毛细胞突触传递缺陷（巴松管突变体）的小鼠突变体中记录了ASSR和ABR。在8周龄时进行研究时，这两种突变体与野生型相比，ASSR和ABR阈值均升高了约40 dB。放大功能有缺陷的小鼠，其ASSR和ABR振幅随声强增加而急剧上升，这可能反映出阈值以上同步激活的神经元成分大量被募集。相比之下，突触传递受损的小鼠的ASSR和ABR反应振幅随声强增加几乎没有变化。总之，ASSR可实现快速、客观且具有频率特异性的听力评估，并且与ABR和耳声发射一起有助于感音神经性听力损失的鉴别诊断。
