Optetrode: a multichannel readout for optogenetic control in freely moving mice.

Optetrode: a multichannel readout for optogenetic control in freely moving mice.
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DOI:
10.1038/nn.2992
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发表时间:
2011-12-04
影响因子:
25
通讯作者:
--
中科院分区:
医学1区
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--
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光遗传学的最新进展提高了在自由运动的哺乳动物中光学控制已定义电路元件的精度;特别是重组酶依赖性视蛋白病毒,与越来越多表达重组酶的转基因小鼠一起使用,可以操纵特定的细胞类型。然而,尽管光遗传控制允许以越来越强大的方式操纵神经回路,但将光遗传刺激与自由移动小鼠中孤立单元的同时多通道电生理读数结合起来仍然是一个挑战。我们设计并验证了光电极,这是一种允许在自由移动的小鼠中进行局部多电极电生理记录和光刺激的设备。Optetrode的制造采用了一种独特的以光纤为中心的同轴设计方法,产生了一种重量轻(2克)、紧凑而坚固的设备,适用于行为正常的老鼠。这种低成本的装置易于建造(无需专门设备2.5小时即可建造)。我们发现驱动器设计产生稳定的高质量记录,并在植入后至少6周内持续这样做。我们首次量化了内侧前额叶皮层细胞对局部光激发和抑制的反应,从而验证了光电极的有效性,在开放的野外探索中探测了小鼠多种不同的遗传定义的细胞类别。
Recent advances in optogenetics have improved the precision with which defined circuit elements can be controlled optically in freely moving mammals; in particular, recombinase-dependent opsin viruses, used with a growing pool of transgenic mice expressing recombinases, allow manipulation of specific cell types. However, although optogenetic control has allowed neural circuits to be manipulated in increasingly powerful ways, combining optogenetic stimulation with simultaneous multichannel electrophysiological readout of isolated units in freely moving mice remains a challenge. We designed and validated the optetrode, a device that allows for colocalized multi-tetrode electrophysiological recording and optical stimulation in freely moving mice. Optetrode manufacture employs a unique optical fiber-centric coaxial design approach that yields a lightweight (2 g), compact and robust device that is suitable for behaving mice. This low-cost device is easy to construct (2.5 h to build without specialized equipment). We found that the drive design produced stable high-quality recordings and continued to do so for at least 6 weeks following implantation. We validated the optetrode by quantifying, for the first time, the response of cells in the medial prefrontal cortex to local optical excitation and inhibition, probing multiple different genetically defined classes of cells in the mouse during open field exploration.
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