Department of Biomedical Engineering, Boston University, Boston, MA 02215, USA.
Department of Biology, Boston University, Boston, MA 02215, USA.
Cell Rep. 2018 Jul 10;24(2):294-303. doi: 10.1016/j.celrep.2018.06.049.
More specific and broadly applicable viral gene-targeting tools for labeling neuron subtypes are needed to advance neuroscience research, especially in rodent transgenic disease models and genetically intractable species. Here, we develop a viral vector that restricts transgene expression to GABAergic interneurons in the rodent neocortex by exploiting endogenous microRNA regulation. Our interneuron-targeting, microRNA-guided neuron tag, "GABA mAGNET," achieves >95% interneuron selective labeling in the mouse cortex, including in a murine model of autism and also some preferential labeling of interneurons in the rat brain. We demonstrate an application of our GABA mAGNET by performing simultaneous, in vivo optogenetic control of two distinct neuron subtypes. This interneuron labeling tool highlights the potential of microRNA-based viral gene targeting to specific neuron subtypes.
需要更具体和广泛适用的病毒基因靶向工具来标记神经元亚型，以推进神经科学研究，特别是在啮齿动物转基因疾病模型和遗传上难以处理的物种中。在这里，我们开发了一种病毒载体，通过利用内源性 microRNA 调控来限制转基因在啮齿动物新皮层中的 GABA 能中间神经元中的表达。我们的中间神经元靶向 microRNA 指导的神经元标签“GABA mAGNET”在小鼠皮层中实现了 >95%的中间神经元选择性标记，包括在自闭症的小鼠模型中，以及在大鼠大脑中一些中间神经元的优先标记。我们通过在体内同时进行两种不同神经元亚型的光遗传学控制来展示我们的 GABA mAGNET 的一种应用。这种中间神经元标记工具突出了基于 microRNA 的病毒基因靶向特定神经元亚型的潜力。
