Keppeler Daniel, Schwaerzle Michael, Harczos Tamas, Jablonski Lukasz, Dieter Alexander, Wolf Bettina, Ayub Suleman, Vogl Christian, Wrobel Christian, Hoch Gerhard, Abdellatif Khaled, Jeschke Marcus, Rankovic Vladan, Paul Oliver, Ruther Patrick, Moser Tobias
Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, 37099 Göttingen, Germany.
Göttingen Graduate Center for Neurosciences and Molecular Biosciences, University of Göttingen, 37075 Göttingen, Germany.
Sci Transl Med. 2020 Jul 22;12(553). doi: 10.1126/scitranslmed.abb8086.
When hearing fails, electrical cochlear implants (eCIs) provide the brain with auditory information. One important bottleneck of CIs is the poor spectral selectivity that results from the wide current spread from each of the electrode contacts. Optical CIs (oCIs) promise to make better use of the tonotopic order of spiral ganglion neurons (SGNs) inside the cochlea by spatially confined stimulation. Here, we established multichannel oCIs based on light-emitting diode (LED) arrays and used them for optical stimulation of channelrhodopsin (ChR)-expressing SGNs in rodents. Power-efficient blue LED chips were integrated onto microfabricated 15-μm-thin polyimide-based carriers comprising interconnecting lines to address individual LEDs by a stationary or mobile driver circuitry. We extensively characterized the optoelectronic, thermal, and mechanical properties of the oCIs and demonstrated stability over weeks in vitro. We then implanted the oCIs into ChR-expressing rats and gerbils, and characterized multichannel optogenetic SGN stimulation by electrophysiological and behavioral experiments. Improved spectral selectivity was directly demonstrated by recordings from the auditory midbrain. Long-term experiments in deafened ChR-expressing rats and in nontreated control animals demonstrated specificity of optogenetic stimulation. Behavioral studies on animals carrying a wireless oCI sound processor revealed auditory percepts. This study demonstrates hearing restoration with improved spectral selectivity by an LED-based multichannel oCI system.
当听力丧失时，电子耳蜗植入物（eCIs）能为大脑提供听觉信息。耳蜗植入物的一个重要瓶颈是频谱选择性差，这是由每个电极触点的电流广泛扩散导致的。光学耳蜗植入物（oCIs）有望通过空间受限刺激更好地利用耳蜗内螺旋神经节神经元（SGNs）的音调顺序。在这里，我们基于发光二极管（LED）阵列建立了多通道光学耳蜗植入物，并将其用于对表达通道视紫红质（ChR）的啮齿动物螺旋神经节神经元进行光刺激。将高能效蓝色LED芯片集成到基于聚酰亚胺的15微米厚的微型载体上，该载体包括互连线，以便通过固定或移动驱动电路对各个LED进行寻址。我们广泛表征了光学耳蜗植入物的光电、热和机械性能，并证明其在体外数周内具有稳定性。然后，我们将光学耳蜗植入物植入表达ChR的大鼠和沙鼠体内，并通过电生理和行为实验对多通道光遗传学螺旋神经节神经元刺激进行了表征。通过听觉中脑的记录直接证明了频谱选择性的改善。在失聪的表达ChR的大鼠和未治疗的对照动物中进行的长期实验证明了光遗传学刺激的特异性。对携带无线光学耳蜗植入物声音处理器的动物进行的行为研究揭示了听觉感知。这项研究证明了基于LED的多通道光学耳蜗植入物系统能够恢复听力并提高频谱选择性。
