Institute for Brain Research, Wuhan Center of Brain Science, Huazhong University of Science and Technology, Wuhan, 430030, China.
Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Cell Mol Neurobiol. 2023 Oct;43(7):3743-3752. doi: 10.1007/s10571-023-01384-y. Epub 2023 Jul 5.
Retrograde tracing is an important method for dissecting neuronal connections and mapping neural circuits. Over the past decades, several virus-based retrograde tracers have been developed and have contributed to display multiple neural circuits in the brain. However, most of the previously widely used viral tools have focused on mono-transsynaptic neural tracing within the central nervous system, with very limited options for achieving polysynaptic tracing between the central and peripheral nervous systems. In this study, we generated a novel mouse line, GT mice, in which both glycoprotein (G) and ASLV-A receptor (TVA) were expressed throughout the body. Using this mouse model, in combination with the well-developed rabies virus tools (RABV-EnvA-ΔG) for monosynaptic retrograde tracing, polysynaptic retrograde tracing can be achieved. This allows functional forward mapping and long-term tracing. Furthermore, since the G-deleted rabies virus can travel upstream against the nervous system as the original strain, this mouse model can also be used for rabies pathological studies. Schematic illustrations about the application principles of GT mice in polysynaptic retrograde tracing and rabies pathological research.
逆行示踪是解析神经元连接和绘制神经回路的重要方法。在过去的几十年中，已经开发出了几种基于病毒的逆行示踪剂，这些示踪剂有助于在大脑中显示多个神经回路。然而，以前广泛使用的大多数病毒工具主要集中在中枢神经系统内的单突触神经示踪，而在中枢和外周神经系统之间实现多突触示踪的选择非常有限。在这项研究中，我们生成了一种新型的 GT 小鼠，该小鼠全身表达糖蛋白（G）和 ASLV-A 受体（TVA）。使用这种小鼠模型，结合已经成熟的狂犬病病毒工具（RABV-EnvA-ΔG）进行单突触逆行示踪，可以实现多突触逆行示踪。这允许进行功能正向映射和长期示踪。此外，由于缺失 G 的狂犬病病毒可以像原始毒株一样沿着神经系统逆行传播，因此该小鼠模型也可用于狂犬病的病理学研究。GT 小鼠在多突触逆行示踪和狂犬病病理学研究中的应用原理示意图。
