Department of Bioengineering, Stanford University, Stanford, California, USA.
Nat Neurosci. 2011 Dec 4;15(1):163-70. doi: 10.1038/nn.2992.
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.
近年来，光遗传学的进展提高了在自由活动的哺乳动物中通过光学手段精确控制特定神经回路元件的能力；特别是，利用越来越多的表达重组酶的转基因小鼠和依赖重组酶的变构光敏感蛋白病毒，使得对特定细胞类型的操控成为可能。然而，尽管光遗传学控制已经使得神经回路能够以越来越强大的方式被操控，但在自由活动的小鼠中结合光遗传学刺激和对分离的单位进行同时的多通道电生理读取仍然是一个挑战。我们设计并验证了 optetrode，这是一种允许在自由活动的小鼠中进行共定位多电极电生理记录和光学刺激的设备。Optetrode 的制造采用了独特的光纤中心同轴设计方法，产生了一种重量轻（2 克）、紧凑且坚固的设备，适用于行为小鼠。这种低成本的设备易于构建（无需专用设备，2.5 小时即可构建）。我们发现，驱动器设计产生了稳定的高质量记录，并且在植入后至少 6 周内仍然如此。我们通过首次量化内侧前额叶皮层细胞对局部光学激发和抑制的反应来验证 optetrode，在小鼠的开放场探索过程中探测了多种不同的遗传定义的细胞类型。
