Development of novel vector systems for neuronal tracing based on recombinant rabies virus vectors.

重组病毒示踪剂可以跨越突触并表达外源基因，对研究神经回路很有用。然而，为了准确和详细地分析神经回路，需要一种控制跨突触传递的技术。我们通过操纵狂犬病病毒的基因组构建了新的狂犬病病毒载体。我们首先删除了载体的糖蛋白基因，以消除其跨突触转移的能力。然后，我们对能够在神经元中高效表达外源基因的载体的恢复系统进行了改进。我们还建立了慢病毒载体和腺相关病毒载体的高效回收系统，以便在灵长类动物的大脑中使用它们。利用这些载体，我们开发了一种新的载体系统，使我们能够在构成大脑中特定路径的特定神经元组中诱导靶基因表达。这些结果表明，本研究建立的病毒载体可以用于选择性和高效的跨突触神经元示踪。

Recombinant viral tracers which can cross synapses and can express foreign genes are useful to study neural circuitry. However, for accurate and detailed analysis of neural circuits, a technique for the control of trans-synaptic transfer is required. We have constructed new rabies virus vectors by manipulating their genome. We first deleted the glycoprotein gene of the vector to extinguish the ability of trans-synaptic transfer from them. Then, we improved recovery systems for the vector which can efficiently express foreign genes in neurons. We also established efficient recovery systems for lentiviral vector and adeno-associated virus vector to use them in the primate brain. Using these vectors, we developed of novel vector system that enables us to induce target gene expression in a specific group of neurons that constitutes a particular pathway in the brain. These results indicate that viral vectors created in this study can be used for selective and efficient transsynaptic neuronal tracing.