Institute for Experimental Epileptology and Cognition Research, University of Bonn, Bonn, Germany.
International Max Planck Research School for Brain and Behavior, University of Bonn, Bonn, Germany.
Front Neural Circuits. 2020 Apr 27;14:16. doi: 10.3389/fncir.2020.00016. eCollection 2020.
Transgenic Cre-recombinase expressing mouse lines are widely used to express fluorescent proteins and opto-/chemogenetic actuators, making them a cornerstone of modern neuroscience. The investigation of interneurons in particular has benefitted from the ability to genetically target specific cell types. However, the specificity of some Cre driver lines has been called into question. Here, we show that nonspecific expression in a subset of hippocampal neurons can have substantial nonspecific functional effects in a somatostatin-Cre (SST-Cre) mouse line. Nonspecific targeting of CA3 pyramidal cells caused large optogenetically evoked excitatory currents in remote brain regions. Similar, but less severe patterns of nonspecific expression were observed in a widely used SST-IRES-Cre line, when crossed with a reporter mouse line. Viral transduction on the other hand yielded more specific expression but still resulted in nonspecific expression in a minority of pyramidal layer cells. These results suggest that a careful analysis of specificity is mandatory before the use of Cre driver lines for opto- or chemogenetic manipulation approaches.
转基因 Cre 重组酶表达小鼠品系广泛用于表达荧光蛋白和光遗传学/化学遗传学激活器，是现代神经科学的基石。特别是中间神经元的研究受益于对特定细胞类型进行基因靶向的能力。然而，一些 Cre 驱动线的特异性已经受到质疑。在这里，我们表明，在 SST-Cre（生长抑素-Cre）小鼠品系中，海马神经元中的亚群中的非特异性表达可能会对其产生实质性的非特异性功能影响。CA3 锥体神经元的非特异性靶向导致远程脑区的光遗传学诱发兴奋性电流增加。当与报告小鼠品系杂交时，在广泛使用的 SST-IRES-Cre 线中观察到类似但程度较轻的非特异性表达模式。另一方面，病毒转导虽然产生了更特异性的表达，但仍导致少数锥体层细胞中的非特异性表达。这些结果表明，在使用 Cre 驱动线进行光遗传学或化学遗传学操作方法之前，必须对特异性进行仔细分析。
