High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics.
High frequency neural spiking and auditory signaling by ultrafast red-shifted optogenetics.
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DOI：
10.1038/s41467-018-04146-3
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发表时间：
2018-05-01
影响因子：
16.6
通讯作者：
Bamberg E
中科院分区：
文献类型：
--
作者：
Mager T;Lopez de la Morena D;Senn V;Schlotte J;D Errico A;Feldbauer K;Wrobel C;Jung S;Bodensiek K;Rankovic V;Browne L;Huet A;Jüttner J;Wood PG;Letzkus JJ;Moser T;Bamberg E
光遗传学革新了神经科学和细胞生物学的基础研究，并具有医学应用的潜力。我们开发的突变体导致一个统一的概念，建设各种通道视紫红质快速关闭动力学。由于不同的吸收最大值，这些通道视紫红质允许在整个可见光谱范围内快速神经光活化。我们将我们的功能分析集中在快速开关，红光激活的Chrimson变体上，因为红光在组织中具有较低的光散射和边缘光毒性。我们的大脑皮层和听觉神经的神经元，快速克里姆森突变体，使神经刺激与几百赫兹的发射频率的范例。它们以高速率和时间保真度驱动尖峰，刺激强度和持续时间的阈值较低。光学耳蜗植入恢复耳聋小鼠的听觉神经活动。这表明突变体促进了神经科学研究和未来的医学应用，如听力恢复。光遗传学应用将受益于具有更快光刺激、增加组织透明度和更低光毒性的通道视紫红质（ChR）。在这里，作者开发了快速红移的ChR变体，并显示了大脑中间神经元的时间精确尖峰和恢复耳聋小鼠听觉活动的能力。
Optogenetics revolutionizes basic research in neuroscience and cell biology and bears potential for medical applications. We develop mutants leading to a unifying concept for the construction of various channelrhodopsins with fast closing kinetics. Due to different absorption maxima these channelrhodopsins allow fast neural photoactivation over the whole range of the visible spectrum. We focus our functional analysis on the fast-switching, red light-activated Chrimson variants, because red light has lower light scattering and marginal phototoxicity in tissues. We show paradigmatically for neurons of the cerebral cortex and the auditory nerve that the fast Chrimson mutants enable neural stimulation with firing frequencies of several hundred Hz. They drive spiking at high rates and temporal fidelity with low thresholds for stimulus intensity and duration. Optical cochlear implants restore auditory nerve activity in deaf mice. This demonstrates that the mutants facilitate neuroscience research and future medical applications such as hearing restoration. Optogenetic applications would benefit from channelrhodopsins (ChRs) with faster photostimulation, increased tissue transparency and lower phototoxicity. Here, the authors develop fast red-shifted ChR variants and show the abilities for temporal precise spiking of cerebral interneurons and restoring auditory activity in deaf mice.
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影响因子：
25
作者：
Lin, John Y.;Knutsen, Per Magne;Muller, Arnaud;Kleinfeld, David;Tsien, Roger Y.
通讯作者：
Tsien, Roger Y.
影响因子：
25
作者：
Kleinlogel, Sonja;Feldbauer, Katrin;Bamberg, Ernst
通讯作者：
Bamberg, Ernst
影响因子：
3.4
作者：
Lin, John Y.;Lin, Michael Z.;Tsien, Roger Y.
通讯作者：
Tsien, Roger Y.
DOI：
10.1007/s10162-007-0108-5
发表时间：
2008-03-01
影响因子：
2.4
作者：
Miller, Charles A.;Hu, Ning;Abbas, Paul J.
通讯作者：
Abbas, Paul J.
影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K