Optogenetic long-term manipulation of behavior and animal development.
Optogenetic long-term manipulation of behavior and animal development.
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DOI：
10.1371/journal.pone.0018766
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发表时间：
2011-04-20
期刊：
影响因子：
3.7
通讯作者：
Gottschalk A
中科院分区：
文献类型：
--
作者：
Schultheis C;Liewald JF;Bamberg E;Nagel G;Gottschalk A
视紫红质-2（ChR 2）被广泛用于神经元的快速光去极化，然而，由于其需要高强度蓝光来激活，因此其不适合于长期体内应用，例如用于行为的操纵或发育期间神经元的光激活。我们使用了在C128残基中具有突变的“慢”ChR 2变体，其在秀丽隐杆线虫中表现出延迟的关闭动力学和增加的光敏感性。在1秒的光脉冲之后，我们可以用低强度的光对神经元和肌肉进行几分钟的光刺激（并且重复短暂的刺激，长达几天）。ChR 2（C128 S）的光激活的命令interneurons引起持久的改变运动。最后，我们可以光学诱导动物发育的深刻变化：ASJ神经元，调节幼虫生长的长期光活化，绕过了daf-11突变体的组成进入“道尔”幼虫状态。这些缺乏鸟苷酸环化酶，这可能使ASJ神经元超极化。此外，光刺激ASJ神经元可急性触发dauer-exit。因此，慢ChR 2可用于长期光活化行为和触发替代动物发育。
Channelrhodopsin-2 (ChR2) is widely used for rapid photodepolarization of neurons, yet, as it requires high-intensity blue light for activation, it is not suited for long-term in vivo applications, e.g. for manipulations of behavior, or photoactivation of neurons during development. We used “slow” ChR2 variants with mutations in the C128 residue, that exhibit delayed off-kinetics and increased light sensitivity in Caenorhabditis elegans. Following a 1 s light pulse, we could photodepolarize neurons and muscles for minutes (and with repeated brief stimulation, up to days) with low-intensity light. Photoactivation of ChR2(C128S) in command interneurons elicited long-lasting alterations in locomotion. Finally, we could optically induce profound changes in animal development: Long-term photoactivation of ASJ neurons, which regulate larval growth, bypassed the constitutive entry into the “dauer” larval state in daf-11 mutants. These lack a guanylyl cyclase, which possibly renders ASJ neurons hyperpolarized. Furthermore, photostimulated ASJ neurons could acutely trigger dauer-exit. Thus, slow ChR2s can be employed to long-term photoactivate behavior and to trigger alternative animal development.
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影响因子：
25
作者：
Boyden, ES;Zhang, F;Deisseroth, K
通讯作者：
Deisseroth, K
影响因子：
9.2
作者：
Nagel, G;Brauner, M;Gottschalk, A
通讯作者：
Gottschalk, A
影响因子：
15
作者：
Radu, Ionela;Bamann, Christian;Heberle, Joachim
通讯作者：
Heberle, Joachim
影响因子：
3.5
作者：
Miranda-Vizuete, A;González, JCF;Swoboda, P
通讯作者：
Swoboda, P
影响因子：
2.7
作者：
CASSADA, RC;RUSSELL, RL
通讯作者：
RUSSELL, RL