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红光大功率光遗传学刺激听觉通路的实用性。

Utility of red-light ultrafast optogenetic stimulation of the auditory pathway.

机构信息

Institute for Auditory Neuroscience and InnerEarLab, University Medical Center Göttingen, Göttingen, Germany.

Göttingen Graduate School for Neurosciences and Molecular Biosciences, University of Göttingen, Göttingen, Germany.

出版信息

EMBO Mol Med. 2021 Jun 7;13(6):e13391. doi: 10.15252/emmm.202013391. Epub 2021 May 7.

Abstract

Optogenetic stimulation of spiral ganglion neurons (SGNs) in the ear provides a future alternative to electrical stimulation used in current cochlear implants. Here, we employed fast and very fast variants of the red-light-activated channelrhodopsin (ChR) Chrimson (f-Chrimson and vf-Chrimson) to study their utility for optogenetic stimulation of SGNs in mice. The light requirements were higher for vf-Chrimson than for f-Chrimson, even when optimizing membrane expression of vf-Chrimson by adding potassium channel trafficking sequences. Optogenetic time and intensity coding by single putative SGNs were compared with coding of acoustic clicks. vf-Chrimson enabled putative SGNs to fire at near-physiological rates with good temporal precision up to 250 Hz of stimulation. The dynamic range of SGN spike rate coding upon optogenetic stimulation was narrower than for acoustic clicks but larger than reported for electrical stimulation. The dynamic range of spike timing, on the other hand, was more comparable for optogenetic and acoustic stimulation. In conclusion, f-Chrimson and vf-Chrimson are promising candidates for optogenetic stimulation of SGNs in auditory research and future cochlear implants.

摘要

光遗传学刺激耳中的螺旋神经节神经元(SGNs)为当前用于耳蜗植入物的电刺激提供了未来的替代方法。在这里,我们使用了红光激活通道蛋白(ChR)Chrimson 的快速和超快变体(f-Chrimson 和 vf-Chrimson),以研究它们在小鼠 SGNs 光遗传学刺激中的应用。即使通过添加钾通道运输序列来优化 vf-Chrimson 的膜表达,vf-Chrimson 的光要求也比 f-Chrimson 高。单个假定的 SGNs 的光遗传学时间和强度编码与声刺激的编码进行了比较。vf-Chrimson 使假定的 SGNs 能够以接近生理的速率以良好的时间精度进行放电,刺激频率高达 250 Hz。光遗传学刺激时 SGN 尖峰速率编码的动态范围比声刺激窄,但比报道的电刺激大。另一方面,尖峰定时的动态范围对于光遗传学和声学刺激更为可比。总之,f-Chrimson 和 vf-Chrimson 是听觉研究和未来耳蜗植入物中 SGN 光遗传学刺激的有前途的候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fb5/8185542/c6a3195df2a8/EMMM-13-e13391-g006.jpg

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