Quantitative chemical composition of cortical GABAergic neurons revealed in transgenic venus-expressing rats
Quantitative chemical composition of cortical GABAergic neurons revealed in transgenic venus-expressing rats
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DOI：
10.1093/cercor/bhm056
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发表时间：
2008-02-01
期刊：
影响因子：
3.7
通讯作者：
Kawaguchi, Yasuo
中科院分区：
文献类型：
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作者：
Uematsu, Masakazu;Hirai, Yasuharu;Kawaguchi, Yasuo
尽管新皮质 GABA 能（γ-氨基丁酸能）中间神经元一直是深入研究的焦点，尤其是在大鼠中，但对于抑制性皮质神经元的功能多样性和组织尚未达成共识。为了更好地分析大鼠中的 GABA 能神经元，我们使用细菌人工染色体 (BAC) 构建体并建立了 2 个转基因大鼠系，它们共表达金星（一种黄色荧光蛋白）和囊泡 GABA 转运蛋白。两种转基因系的大脑 GABA 含量与野生型大鼠的水平相似。在额叶皮质中，Venus 在超过 95% 的 GABA 能神经元中表达，其中大多数还表达 6 种生化标记物中的至少一种，包括 α-actitin-2，它优先标记晚期尖峰神经胶质细胞。利用金星表达允许对所有类别的非锥体细胞进行有针对性的记录（无论其体细胞形态如何）这一事实，我们证明了快速尖峰神经元（其体细胞大小和垂直树突投影是异质的）具有相对均匀的水平尺寸，表明细胞类型特异性的柱状输入区域。我们的数据证明了 VGAT-Venus 大鼠对于研究 GABA 能回路的好处，以及在大鼠中使用 BAC 技术来标记特定的、基因定义的神经元子集的可行性。
Although neocortical GABAergic (gamma-aminobutyric acidergic) interneurons have been the focus of intense study, especially in the rat, a consensus view of the functional diversity and organization of inhibitory cortical neurons has not yet been achieved. To better analyze GABAergic neurons in the rat, we used a bacterial artificial chromosome (BAC) construct and established 2 lines of transgenic rats that coexpress Venus, a yellow fluorescent protein, with the vesicular GABA transporter. The brain GABA content from both transgenic lines was similar to the level found in wild-type rats. In the frontal cortex, Venus was expressed in >95% of GABAergic neurons, most of which also expressed at least one of 6 biochemical markers, including alpha-actitin-2, which preferentially labeled late-spiking neurogliaform cells. Taking advantage of the fact that Venus expression allows for targeted recording from all classes of nonpyramidal cells, irrespective of their somatic morphologies, we demonstrated that fast-spiking neurons, which were heterogeneous in somatic size as well as vertical dendritic projection, had relatively uniform horizontal dimensions, suggesting a cell type-specific columnar input territory. Our data demonstrate the benefits of VGAT-Venus rats for investigating GABAergic circuits, as well as the feasibility of using BAC technology in rats to label subsets of specific, genetically defined neurons.