A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila.

A Genetic Toolkit for Dissecting Dopamine Circuit Function in Drosophila.
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DOI:
10.1016/j.celrep.2018.03.068
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发表时间:
2018-04-10
期刊:
影响因子:
8.8
通讯作者:
Wu MN
Wu MN
中科院分区:
生物学1区
文献类型:
--
作者:
Xie T;Ho MCW;Liu Q;Horiuchi W;Lin CC;Task D;Luan H;White BH;Potter CJ;Wu MN

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神经调质多巴胺(DA)在运动控制、动机行为和高阶认知过程中起着关键作用。要剖析这些DA神经网络如何调整局部神经回路的活动来调节行为,需要操纵小规模DA神经元的工具。为了满足这一需求,我们组装了一个遗传工具包,可以对果蝇的DA神经网络进行精细的控制。为了进一步完善特定DA神经元的靶向,我们还创建了允许将任何现有GAL4系转化为分裂GAL4或GAL80系的试剂。我们演示了如何使用这个工具包与最近开发的计算方法,以快速生成额外的试剂,用于操纵小的子集或单个DA神经元。最后,我们使用的工具包,揭示了一个小的DA神经元和饲养条件的社会空间行为测定之间的动态相互作用。多巴胺能回路如何调节行为的快速分析受到可用于靶向和操纵少量这些神经元的遗传工具的限制。Xie等人提出了果蝇中的遗传工具,其允许合理靶向稀疏多巴胺能神经元亚群和选择性敲除多巴胺信号。
The neuromodulator dopamine (DA) plays a key role in motor control, motivated behaviors, and higher-order cognitive processes. Dissecting how these DA neural networks tune the activity of local neural circuits to regulate behavior requires tools for manipulating small groups of DA neurons. To address this need, we assembled a genetic toolkit that allows for an exquisite level of control over the DA neural network in Drosophila. To further refine targeting of specific DA neurons, we also created reagents that allow for the conversion of any existing GAL4 line into Split GAL4 or GAL80 lines. We demonstrated how this toolkit can be used with recently developed computational methods to rapidly generate additional reagents for manipulating small subsets or individual DA neurons. Finally, we used the toolkit to reveal a dynamic interaction between a small subset of DA neurons and rearing conditions in a social space behavioral assay. The rapid analysis of how dopaminergic circuits regulate behavior is limited by the genetic tools available to target and manipulate small numbers of these neurons. Xie et al. present genetic tools in Drosophila that allow rational targeting of sparse dopaminergic neuronal subsets and selective knockdown of dopamine signaling.
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