A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing.
A light-gated, potassium-selective glutamate receptor for the optical inhibition of neuronal firing.
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DOI：
10.1038/nn.2589
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发表时间：
2010-08
影响因子：
25
通讯作者：
Isacoff, Ehud Y.
中科院分区：
文献类型：
--
作者：
Janovjak, Harald;Szobota, Stephanie;Wyart, Claire;Trauner, Dirk;Isacoff, Ehud Y.
遗传靶向的光激活离子通道和泵使得确定特定神经元在神经元回路、信息处理和行为中的作用成为可能。在这里，我们描述了一种K+选择性离子型谷氨酸受体的发展，可逆地抑制神经元的活动，在解离的神经元和脑片中的光响应，可逆地抑制行为在斑马鱼。该受体是K+选择性细菌谷氨酸受体的孔区和光门控哺乳动物红藻氨酸受体（iGluR 6/GluK 2）的配体结合结构域的嵌合体。这种超极化光门控通道HyLighter由一个波长的短暂光脉冲打开，并由第二个波长的脉冲关闭。在中等强度下获得对照。光激活后，光电流和光沉默的活动在黑暗中持续很长一段时间。HyLighter的低光照要求和双稳定性代表了神经回路解剖的优势。
Genetically targeted light-activated ion channels and pumps make it possible to determine the role of specific neurons in neuronal circuits, information processing and behavior. Here, we describe the development of a K+-selective ionotropic glutamate receptor that reversibly inhibits neuronal activity in response to light in dissociated neurons and brain slice and reversibly suppresses behavior in zebrafish. The receptor is a chimera of the pore region of a K+-selective bacterial glutamate receptor and the ligand binding domain of the light-gated mammalian kainate receptor (iGluR6/GluK2). This hyperpolarizing light-gated channel, HyLighter, is turned on by a brief light pulse at one wavelength and turned off by a pulse at a second wavelength. The control is obtained at moderate intensity. After optical activation, the photo-current and optical silencing of activity persist in the dark for extended periods. The low light requirement and bi-stability of HyLighter represent advantages for the dissection of neural circuitry.
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