A bright future? Optogenetics in the periphery for pain research and therapy.
A bright future? Optogenetics in the periphery for pain research and therapy.
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DOI：
10.1097/j.pain.0000000000001329
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发表时间：
2018-09
期刊：
影响因子：
7.4
通讯作者：
Gereau RW 4th
中科院分区：
文献类型：
--
作者：
Mickle AD;Gereau RW 4th
光遗传学描述了在遗传和/或解剖学上受限制的细胞群体中表达光激活蛋白（称为视蛋白）的技术，允许暂时精确和选择性地操纵目标群体的活性。这使得剖析特定神经元群体在疼痛处理的不同阶段的生理作用成为可能（也在参考文献14,22,83中进行了审查）。从莱茵衣藻（Chlamydomonas reinhardtii）中克隆出来的光激活阳离子通道——通道视紫红质-2 （ChR2）的靶向神经元表达首次证明了光激活通道可以操纵神经元活动。自这一发现以来，各种各样的视蛋白已经在自然界中被发现或被改造以允许以时间精确和细胞类型特异性的方式操纵神经元活动（去极化/激活或超极化/抑制）18,45,46,64,115，细胞内信号，1,60,96,102,103和基因表达32,89,97（参见参考文献33,49,62,77）。突变和基因组筛选扩大了视蛋白工具箱，包括具有更快动力学的视蛋白，允许更精确地控制活性模式；双稳定视蛋白6，仅用短暂的光脉冲即可持续激活或抑制；并且在更长的波长下激活的视蛋白（红移视蛋白）20,63允许改善光穿透组织。除了对膜电位的直接影响外，其他视蛋白，其中大多数是经过分子工程改造的，可以启动更复杂的信号传导过程，如g蛋白偶联受体（GPCR）下游信号传导1,60,102,103和基因表达调控。32,89,97这些视蛋白扩展了光遗传学操作的优势，超越了对膜电位的直接影响，进一步扩大了这些方法在操作可兴奋和不可兴奋细胞中的效用。这种不断扩展的光遗传学工具为操纵细胞中的活动和信号提供了许多优雅的方法，并导致了系统神经科学中新发现的爆炸式增长。然而，光遗传学在周围神经系统（PNS）研究中的广泛应用存在两个主要障碍。首先，与中枢神经系统（CNS）的应用相比，病毒和转基因工具更有限，更不成熟，因此在PNS神经元中产生一致和强大的遗传限制性视蛋白表达存在挑战。第二个挑战是向表达这些视蛋白的神经元持续且受限地传递光。克服这些障碍对于实现PNS中光遗传操作的全部潜力至关重要。
Optogenetics describes the technique of expressing lightactivatable proteins, called opsins, in a genetically and/or anatomically restricted population of cells, permitting temporally precise and selective manipulation of the activity of the targeted population. This makes it possible to dissect the physiological role of specific neuronal populations in different phases of pain processing (also reviewed in Refs. 14, 22, 83). Targeted neuronal expression of channelrhodopsin-2 (ChR2), a light-activated cation channel cloned from the single-cell algae Chlamydomonas reinhardtii, provided the first evidence that optically activated channels can manipulate neuronal activity. 13 Since this discovery, a wide variety of opsins have been identified in nature or engineered to permit manipulation of neuronal activity (depolarization/activation or hyperpolarization/inhibition), 18, 45, 46, 56, 64,115 intracellular signaling, 1, 60, 96,102,103 and gene expression32, 89, 97 in a temporally precise and cell-type–specific manner (reviewed in Refs. 33, 49, 62, 77). Mutagenesis and genomic screening has expanded the opsin tool box to include opsins with faster kinetics, 5, 48 permitting more precise control of activity patterns; bistable opsins, 6 permitting sustained activation or inhibition with only brief light pulses; and opsins activated at longer wavelengths (red-shifted opsins), 20, 63 permitting improved light penetration through tissues. In addition to direct effects on membrane potential, other opsins, most of which have been molecularly engineered, can initiate more complex signaling processes, such as G-protein-coupled receptor (GPCR) downstream signaling1, 60,102,103 and regulation of gene expression. 32, 89, 97 These opsins extend the advantages of optogenetic manipulations beyond direct effects on membrane potential, furthering the utility of these approaches in manipulating both excitable and nonexcitable cells. This ever-expanding set of optogenetic tools has provided many elegant approaches for manipulating activity and signaling in cells, and has led to an explosion of new findings in systems neuroscience. However, widespread implementation of optogenetics in studies of the peripheral nervous system (PNS) presents 2 major obstacles. The first is that there are challenges in producing consistent and robust genetically restricted expression of opsins in neurons of the PNS, as viral and transgenic tools are more limited and less established as compared to central nervous system (CNS) applications. The second challenge is consistent and restricted delivery of light to the neurons expressing these opsins. Overcoming these obstacles is critical to realizing the full potential of optogenetic manipulations in the PNS.
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影响因子：
7.4
作者：
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16.2
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25
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