Spatio-temporal control of neural activity in vivo using fluorescence microendoscopy
Spatio-temporal control of neural activity in vivo using fluorescence microendoscopy
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DOI：
10.1111/j.1460-9568.2012.08191.x
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发表时间：
2012-09-01
影响因子：
3.4
通讯作者：
Funabiki, Kazuo
中科院分区：
文献类型：
--
作者：
Hayashi, Yuichiro;Tagawa, Yoshiaki;Funabiki, Kazuo
为了研究神经回路动力学如何控制动物的行为，需要以高时空分辨率控制神经活动。传统的操纵神经活动的方法，如电微刺激或药物阻断，具有较差的空间和/或时间分辨率。藻类蛋白通道视紫红质-2(ChR2)使神经活动能够进行毫秒级的精确控制。然而，用于体内高空间分辨率定位的光刺激方法尚未建立。在这里，我们报道了一种新型的光电探头，由光纤束和金属电极组成。光纤束被用作脑内插入式内窥镜，用于图像传输和刺激光传递。用内窥镜上捆绑的电极检测到ChR2表达神经元的光诱导活动，从而能够验证光诱发动作电位。在第5层皮层神经元中表达ChR2的转基因小鼠通过光纤束进行光刺激，导致单须移动，表明体内神经元的空间激活受到限制。这里描述的探测系统和各种光活性分子的组合将有助于研究特定神经活动模式和行为之间的因果联系。
Controlling neural activity with high spatio-temporal resolution is desired for studying how neural circuit dynamics control animal behavior. Conventional methods for manipulating neural activity, such as electrical microstimulation or pharmacological blockade, have poor spatial and/or temporal resolution. Algal protein channelrhodopsin-2 (ChR2) enables millisecond-precision control of neural activity. However, a photostimulation method for high spatial resolution mapping in vivo is yet to be established. Here, we report a novel optical/electrical probe, consisting of optical fiber bundles and metal electrodes. Optical fiber bundles were used as a brain-insertable endoscope for image transfer and stimulating light delivery. Light-induced activity from ChR2-expressing neurons was detected with electrodes bundled to the endoscope, enabling verification of light-evoked action potentials. Photostimulation through optical fiber bundles of transgenic mice expressing ChR2 in layer 5 cortical neurons resulted in single-whisker movement, indicating spatially restricted activation of neurons in vivo. The probe system described here and a combination of various photoactive molecules will facilitate studies on the causal link between specific neural activity patterns and behavior.