Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex.
Strategies and Tools for Combinatorial Targeting of GABAergic Neurons in Mouse Cerebral Cortex.
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小鼠大脑皮层 GABA 神经元组合靶向的策略和工具
DOI：
10.1016/j.neuron.2016.08.021
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发表时间：
2016-09-21
期刊：
影响因子：
16.2
通讯作者：
Huang ZJ
中科院分区：
文献类型：
--
作者：
He M;Tucciarone J;Lee S;Nigro MJ;Kim Y;Levine JM;Kelly SM;Krugikov I;Wu P;Chen Y;Gong L;Hou Y;Osten P;Rudy B;Huang ZJ
系统的遗传进入GABA能细胞类型将有助于研究抑制回路的功能和发展。然而，单基因驱动的重组酶系标志着相对较宽和异质细胞群。尽管交叉方法提高了精度，但尚不清楚它们是否可以捕获由多个特征定义的细胞类型。在这里，我们证明了组合遗传和病毒方法的目标是受限制的GABA能亚群和细胞类型，其特征在于不同的层流位置，形态，轴突投影和电生理特性。胚胎交易转录因子驱动因素允许对祖细胞池的命运映射，从而产生不同的Gabaergic种群，包括层流组。祖细胞命运限制信号转换为本构重组酶表达，可以根据细胞类型的谱系和出生时间对病毒靶向。正确设计的交叉点，减法，转换和多色记者可以增强驱动程序和病毒载体的精度和多功能性。这些策略和工具将有助于研究整个小鼠大脑的GABA能神经元。
他等人。目前的策略和工具用于小鼠大脑中GABA能神经元组合靶向。特定的细胞类型靶向可以通过将2至3个驱动器 - 重复蛋白等位基因与具有多个细胞定义特征的病毒矢量相结合。
Systematic genetic access to GABAergic cell types will facilitate studying the function and development of inhibitory circuitry. However, single gene-driven recombinase lines mark relatively broad and heterogeneous cell populations. Although intersectional approaches improve precision, it remains unclear whether they can capture cell types defined by multiple features. Here we demonstrate that combinatorial genetic and viral approaches target restricted GABAergic subpopulations and cell types characterized by distinct laminar location, morphology, axonal projection, and electrophysiological properties. Intersectional embryonic transcription factor drivers allow finer fate mapping of progenitor pools that give rise to distinct GABAergic populations, including laminar cohorts. Conversion of progenitor fate restriction signals to constitutive recombinase expression enables viral targeting of cell types based on their lineage and birth time. Properly designed intersection, subtraction, conversion, and multi-color reporters enhance the precision and versatility of drivers and viral vectors. These strategies and tools will facilitate studying GABAergic neurons throughout the mouse brain. He et al. present strategies and tools for the combinatorial targeting of GABAergic neurons in the mouse brain. Specific cell type targeting can be achieved by combining 2 to 3 driver-reporter alleles with viral vectors that engage multiple cell-defining features.
影响因子：
3.5
作者：
Tricoire L;Kubota Y;Cauli B
通讯作者：
Cauli B