Near-infrared (NIR) optogenetics using up-conversion system
Near-infrared (NIR) optogenetics using up-conversion system
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使用上转换系统的近红外 (NIR) 光遗传学
DOI：
10.1117/12.2078875
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Hiromu Yawo
中科院分区：
文献类型：
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作者：
Shoko Hososhima;Hideya Yuasa;Toru Ishizuka;Hiromu Yawo
人们期待已久的非侵入性远程控制技术，旨在操纵神经功能，以全面和定量地了解大脑中的神经元网络以及治疗神经系统疾病。最近，它已经成为可能的光学操纵神经元的活动，使用生物光反应分子，如通道视紫红质-2（ChR 2）。然而，ChR 2及其亲属大多对不能有效穿透生物组织的可见光反应。相比之下，近红外（NIR）光穿透到组织深处，因为生物系统在这个所谓的“成像窗口”内几乎是透明的。在这里，我们使用由稀土元素组成的镧系纳米颗粒（LNP）作为发光体来激活通道视紫红质（ChR），因为它们吸收低能量的近红外光以发射高能量的可见光（上转换）。将神经胶质瘤杂交ND-7/23细胞与LNP（NaYF 4：Sc/Yb/Er）颗粒（峰值发射，543 nm）一起培养，并转染以表达C1 V1（峰值吸光度，539 nm），C1 V1是ChR 1和VChR 1的嵌合体。响应于NIR激光（976 nm）产生光电流，其水平与过滤的Hg灯（530-550 nm）引起的光电流相当。近红外光脉冲还在表达C1 V1的培养神经元中诱发动作电位。这表明，从LNP发射的绿色发光有效地激活了C1 V1以产生光电流。通过对LNP、受体光反应生物分子和光学器件的优化，该系统可以应用于无创驱动大脑深处的神经元。
Non-invasive remote control technologies designed to manipulate neural functions for a comprehensive and quantitative understanding of the neuronal network in the brain as well as for the therapy of neurological disorders have long been awaited. Recently, it has become possible to optically manipulate the neuronal activity using biological photo-reactive molecules such as channelrhodopsin-2 (ChR2). However, ChR2 and its relatives are mostly reactive to visible light which does not effectively penetrate through biological tissues. In contrast, near-infrared (NIR) light penetrates deep into the tissues because biological systems are almost transparent to light within this so-called ‘imaging window’. Here we used lanthanide nanoparticles (LNPs), which are composed of rare-earth elements, as luminous bodies to activate channelrhodopsins (ChRs) since they absorb low-energy NIR light to emit high-energy visible light (up-conversion). Neuron-glioma-hybrid ND-7/23 cells were cultured with LNP(NaYF4:Sc/Yb/Er) particles (peak emission, 543 nm) and transfected to express C1V1 (peak absorbance, 539 nm), a chimera of ChR1 and VChR1. The photocurrents were generated in response to NIR laser light (976 nm) to a level comparable to that evoked by a filtered Hg lamp (530-550 nm). NIR light pulses also evoked action potentials in the cultured neurons that expressed C1V1. It is suggested that the green luminescent light emitted from LNPs effectively activated C1V1 to generate the photocurrent. With the optimization of LNPs, acceptor photo-reactive biomolecules and optics, this system could be applied to non-invasively actuate neurons deep in the brain.