Ultrafast optogenetic control

Ultrafast optogenetic control
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DOI:
10.1038/nn.2495
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发表时间:
2010-03-01
影响因子:
25
通讯作者:
Hegemann, Peter
Hegemann, Peter
中科院分区:
医学1区
文献类型:
--
作者:
Gunaydin, Lisa A.;Yizhar, Ofer;Hegemann, Peter

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通道视紫红质,如通道视紫红质-2 (ChR2)可以在多种细胞、组织和动物物种中以毫秒级的精度驱动峰值。然而,该蛋白的一些特性限制了光遗传控制的精度。首先,当ChR2在高水平表达时,额外的尖峰(例如,双峰)可能在响应单个光脉冲时发生,这可能意味着双峰可能对神经编码很重要。其次,在持续的序列中,许多细胞不能跟随chr2驱动的伽马(类似于40 Hz)范围以上的峰值,从而阻止了暂时静止的光遗传进入广泛而重要的神经信号带。最后,快速的光驱动尖峰序列可以导致10 mV或更高的平台电位,导致附带的信息处理影响的上状态。我们设计并验证了一种工程视蛋白基因(ChETA),该基因解决了所有这些限制(大大减少了额外的峰值,消除了平台电位,并允许暂时静止,持续的峰值序列至少达到200hz)。
Channelrhodopsins such as channelrhodopsin-2 (ChR2) can drive spiking with millisecond precision in a wide variety of cells, tissues and animal species. However, several properties of this protein have limited the precision of optogenetic control. First, when ChR2 is expressed at high levels, extra spikes ( for example, doublets) can occur in response to a single light pulse, with potential implications as doublets may be important for neural coding. Second, many cells cannot follow ChR2-driven spiking above the gamma (similar to 40 Hz) range in sustained trains, preventing temporally stationary optogenetic access to a broad and important neural signaling band. Finally, rapid optically driven spike trains can result in plateau potentials of 10 mV or more, causing incidental upstates with information-processing implications. We designed and validated an engineered opsin gene (ChETA) that addresses all of these limitations ( profoundly reducing extra spikes, eliminating plateau potentials and allowing temporally stationary, sustained spike trains up to at least 200 Hz).