Siegert Sandra, Scherf Brigitte Gross, Del Punta Karina, Didkovsky Nick, Heintz Nathaniel, Roska Botond
Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland.
Nat Neurosci. 2009 Sep;12(9):1197-204. doi: 10.1038/nn.2370. Epub 2009 Aug 2.
The mammalian brain is assembled from thousands of neuronal cell types that are organized in distinct circuits to perform behaviorally relevant computations. Transgenic mouse lines with selectively marked cell types would facilitate our ability to dissect functional components of complex circuits. We carried out a screen for cell type-specific green fluorescent protein expression in the retina using BAC transgenic mice from the GENSAT project. Among others, we identified mouse lines in which the inhibitory cell types of the night vision and directional selective circuit were selectively labeled. We quantified the stratification patterns to predict potential synaptic connectivity between marked cells of different lines and found that some of the lines enabled targeted recordings and imaging of cell types from developing or mature retinal circuits. Our results suggest the potential use of a stratification-based screening approach for characterizing neuronal circuitry in other layered brain structures, such as the neocortex.
哺乳动物的大脑由数千种神经元细胞类型组成,这些细胞类型以不同的回路组织起来,以执行与行为相关的计算。具有选择性标记细胞类型的转基因小鼠品系将有助于我们剖析复杂回路的功能组件。我们使用来自GENSAT项目的BAC转基因小鼠对视网膜中细胞类型特异性绿色荧光蛋白表达进行了筛选。其中,我们鉴定出了一些小鼠品系,其中夜视和方向选择性回路的抑制性细胞类型被选择性标记。我们对分层模式进行了量化,以预测不同品系标记细胞之间潜在的突触连接性,并发现其中一些品系能够对发育中的或成熟的视网膜回路中的细胞类型进行靶向记录和成像。我们的结果表明,基于分层的筛选方法有可能用于表征其他分层脑结构(如新皮层)中的神经元回路。