An optical neural interface:: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology
An optical neural interface:: in vivo control of rodent motor cortex with integrated fiberoptic and optogenetic technology
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DOI：
10.1088/1741-2560/4/3/s02
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发表时间：
2007-09-01
影响因子：
4
通讯作者：
Deisseroth, Karl
中科院分区：
文献类型：
--
作者：
Aravanis, Alexander M.;Wang, Li-Ping;Deisseroth, Karl
神经接口技术近年来取得了巨大的进步，但刺激电极仍然无法可靠地靶向神经组织内的特定细胞类型（例如兴奋性或抑制性神经元）。这一障碍具有重大的科学和临床意义。例如，医生、神经工程师和神经科学家之间就脑深部电刺激（DBS）过程中招募的相关细胞类型存在激烈的争论;此外，DBS的许多使人衰弱的副作用可能是由于缺乏细胞类型特异性。我们在这里描述了一种新的光学神经接口技术，将允许神经工程师以毫秒级的时间精度在体内光学寻址特定的细胞类型。藻视紫红质-2（ChR 2）是我们开发用于哺乳动物的藻类光激活离子通道，可以在毫秒的时间尺度上产生安全的光驱动CNS神经元刺激。由于ChR 2是遗传靶向的，即使稀疏嵌入完整电路中的特定神经元群体也可以以高时间精度刺激。在这里，我们报告了第一个在完整的动物体内的功能性光学神经接口（ONI）的行为演示，涉及集成的光纤和光遗传学技术。我们开发了一种固态激光二极管系统，该系统可以以毫秒级精度进行脉冲，在473 nm处输出20 mW的功率，并且耦合到直径类似于200 μ m的轻质柔性多模光纤。为了利用该系统的独特优势，我们在体内用CaMKII α启动子特异性地将ChR 2靶向兴奋性细胞。在这些条件下，离开纤维的光的强度（类似于380 mW mm（-2））足以驱动体内的兴奋性神经元，并在完整的啮齿动物中通过行为输出控制运动皮层功能。在任何时候都不需要外源性化学辅因子，这是大型哺乳动物体内研究的一个重要发现。通过光学控制神经元亚型来实现行为调节可能会产生基本的网络水平的见解，补充电极方法学教给我们的内容，并且新兴的光遗传学工具包可能会在广泛的神经科学，神经工程和临床问题中找到应用。
Neural interface technology has made enormous strides in recent years but stimulating electrodes remain incapable of reliably targeting specific cell types (e.g. excitatory or inhibitory neurons) within neural tissue. This obstacle has major scientific and clinical implications. For example, there is intense debate among physicians, neuroengineers and neuroscientists regarding the relevant cell types recruited during deep brain stimulation (DBS); moreover, many debilitating side effects of DBS likely result from lack of cell-type specificity. We describe here a novel optical neural interface technology that will allow neuroengineers to optically address specific cell types in vivo with millisecond temporal precision. Channelrhodopsin-2 (ChR2), an algal light-activated ion channel we developed for use in mammals, can give rise to safe, light-driven stimulation of CNS neurons on a timescale of milliseconds. Because ChR2 is genetically targetable, specific populations of neurons even sparsely embedded within intact circuitry can be stimulated with high temporal precision. Here we report the first in vivo behavioral demonstration of a functional optical neural interface (ONI) in intact animals, involving integrated fiberoptic and optogenetic technology. We developed a solid-state laser diode system that can be pulsed with millisecond precision, outputs 20 mW of power at 473 nm, and is coupled to a lightweight, flexible multimode optical fiber, similar to 200,mu m in diameter. To capitalize on the unique advantages of this system, we specifically targeted ChR2 to excitatory cells in vivo with the CaMKII alpha promoter. Under these conditions, the intensity of light exiting the fiber (similar to 380 mW mm(-2)) was sufficient to drive excitatory neurons in vivo and control motor cortex function with behavioral output in intact rodents. No exogenous chemical cofactor was needed at any point, a crucial finding for in vivo work in large mammals. Achieving modulation of behavior with optical control of neuronal subtypes may give rise to fundamental network-level insights complementary to what electrode methodologies have taught us, and the emerging optogenetic toolkit may find application across a broad range of neuroscience, neuroengineering and clinical questions.