Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37075 Göttingen, Germany.
Collaborative Research Center 889, University of Göttingen, 37075 Göttingen, Germany.
Sci Transl Med. 2018 Jul 11;10(449). doi: 10.1126/scitranslmed.aao0540.
Cochlear implants partially restore hearing via direct electrical stimulation of spiral ganglion neurons (SGNs). However, spread of excitation from each electrode limits spectral coding. We explored the use of optogenetics to deliver spatially restricted and cell-specific excitation in the cochlea of adult Mongolian gerbils. Adeno-associated virus carrying the gene encoding the light-sensitive calcium translocating channelrhodopsin (CatCh) was injected into the cochlea of adult gerbils. SGNs in all cochlea turns showed stable and long-lasting CatCh expression, and electrophysiological recording from single SGNs showed that light stimulation up to few hundred Hertz induced neuronal firing. We characterized the light-induced activity in the auditory pathway by electrophysiological and behavioral analysis. Light- and sound-induced auditory brainstem responses showed similar kinetics and amplitude. In normal hearing adult gerbils, optical cochlear implants elicited stable optical auditory brainstem responses over a period of weeks. In normal hearing animals, light stimulation cued avoidance behavior that could be reproduced by subsequent acoustic stimulation, suggesting similar perception of light and acoustic stimuli. Neurons of the primary auditory cortex of normal hearing adult gerbils responded with changes in firing rates with increasing light intensity. In deaf adult gerbils, light stimulation generated auditory responses and cued avoidance behavior indicating partial restoration of auditory function. Our data show that optogenetic cochlear stimulation achieved good temporal fidelity with low light intensities in an adult rodent model, suggesting that optogenetics might be used to develop cochlear implants with improved restorative capabilities.
耳蜗植入物通过对螺旋神经节神经元(SGN)的直接电刺激来部分恢复听力。然而,每个电极的兴奋传播限制了频谱编码。我们探索了使用光遗传学在成年蒙古沙鼠的耳蜗中提供空间受限和细胞特异性的兴奋。携带编码光敏感钙转运通道视紫红质(CatCh)的基因的腺相关病毒被注入成年沙鼠的耳蜗。所有耳蜗转位的 SGN 均显示出稳定且持久的 CatCh 表达,并且来自单个 SGN 的电生理记录表明,光刺激高达数百赫兹可诱导神经元放电。我们通过电生理和行为分析来描述听觉通路中的光诱导活性。光和声音诱导的听觉脑干反应具有相似的动力学和幅度。在正常听力的成年沙鼠中,光学耳蜗植入物在数周的时间内可产生稳定的光学听觉脑干反应。在正常听力的动物中,光刺激提示回避行为,随后的声学刺激可以重现该行为,这表明对光和声学刺激的感知相似。正常听力的成年沙鼠初级听觉皮层的神经元随着光强度的增加而以放电率的变化做出反应。在失聪的成年沙鼠中,光刺激产生听觉反应并提示回避行为,表明听觉功能部分恢复。我们的数据表明,在成年啮齿动物模型中,光遗传学耳蜗刺激以低光强度实现了良好的时间保真度,这表明光遗传学可能用于开发具有改善的恢复能力的耳蜗植入物。