Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons.
Using a bistable animal opsin for switchable and scalable optogenetic inhibition of neurons.
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DOI：
10.15252/embr.202051866
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发表时间：
2021-05-05
期刊：
影响因子：
7.7
通讯作者：
Lucas RJ
中科院分区：
文献类型：
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作者：
Rodgers J;Bano-Otalora B;Belle MDC;Paul S;Hughes R;Wright P;McDowell R;Milosavljevic N;Orlowska-Feuer P;Martial FP;Wynne J;Ballister ER;Storchi R;Allen AE;Brown T;Lucas RJ
关于最佳抑制性光遗传学工具没有共识。由于Gi/o信号传导是神经元抑制的天然机制，我们询问七鳃鳗副视蛋白（“灯光”），一种Gi/o偶联的哺乳动物视蛋白，是否可以用于光遗传学沉默。我们表明，短（405 nm）和长（525 nm）波长脉冲重复开关灯之间的稳定信号的活动和非活动状态，分别，并结合这些波长可以用来实现中间水平的活动。这些特性可用于产生可切换的神经元超极化和抑制小鼠下丘脑视交叉上核中的自发尖峰放电。在（主要）ON双极细胞中表达Lamplight可以在晚期光感受器变性后使视网膜光敏化，其中405和525 nm刺激在视网膜的输出神经元中产生相反符号的响应。我们得出结论，哺乳动物视蛋白可以协同内源性信号传导机制，以允许可扩展、持续和可逆的光遗传学抑制。七鳃鳗副视蛋白是一种Gi/o-偶联的哺乳动物视蛋白，分别由短波长和长波长光激活和失活。这项研究表明，Lamplight可以用作小鼠中可逆的抑制性光遗传学工具。
There is no consensus on the best inhibitory optogenetic tool. Since Gi/o signalling is a native mechanism of neuronal inhibition, we asked whether Lamprey Parapinopsin (“Lamplight”), a Gi/o‐coupled bistable animal opsin, could be used for optogenetic silencing. We show that short (405 nm) and long (525 nm) wavelength pulses repeatedly switch Lamplight between stable signalling active and inactive states, respectively, and that combining these wavelengths can be used to achieve intermediate levels of activity. These properties can be applied to produce switchable neuronal hyperpolarisation and suppression of spontaneous spike firing in the mouse hypothalamic suprachiasmatic nucleus. Expressing Lamplight in (predominantly) ON bipolar cells can photosensitise retinas following advanced photoreceptor degeneration, with 405 and 525 nm stimuli producing responses of opposite sign in the output neurons of the retina. We conclude that bistable animal opsins can co‐opt endogenous signalling mechanisms to allow optogenetic inhibition that is scalable, sustained and reversible. Lamprey parapinopsin is a Gi/o‐coupled bistable animal opsin activated and deactivated by short and long wavelength light, respectively. This study shows that Lamplight can be used as a reversible inhibitory optogenetic tool in mice.