Rabies Virus Pseudotyped with CVS-N2C Glycoprotein as a Powerful Tool for Retrograde Neuronal Network Tracing
1 Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, Guangdong Provincial Key Laboratory of Brain Connectome and Behavior, CAS Center for Excellence in Brain Science and Intelligence Technology, Brain Cognition and Brain Disease Institute (BCBDI), Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions, Shenzhen 518055, China
2 State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, China
3 Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430071, China
4 College of Life Sciences, Wuhan University, Wuhan 430071, China
5 School of Human and Social Sciences, University of West London, London, UK
6 University of the Chinese Academy of Sciences, Beijing 100049, China
Abstract
Efficient viral vectors for mapping and manipulating long-projection neuronal circuits are crucial in structural and functional studies of the brain. The SAD strain rabies virus with the glycoprotein gene deleted pseudotyped with the N2C glycoprotein (SAD-RV(ΔG)-N2C(G)) shows strong neuro-tropism in cell culture, but its in vivo efficiency for retrograde gene transduction and neuro-tropism have not been systematically characterized. We compared these features in different mouse brain regions for SAD-RV-N2C(G) and two other widely-used retrograde tracers, SAD-RV(ΔG)-B19(G) and rAAV2-retro. We found that SAD-RV(ΔG)-N2C(G) enhanced the infection efficiency of long-projecting neurons by ~10 times but with very similar neuro-tropism, compared with SAD-RV(ΔG)-B19(G). On the other hand, SAD-RV(ΔG)-N2C(G) had an infection efficiency comparable with rAAV2-retro, but a more restricted diffusion range, and broader tropism to different types and regions of long-projecting neuronal populations. These results demonstrate that SAD-RV(ΔG)-N2C(G) can serve as an effective retrograde vector for studying neuronal circuits.
Keywords
Viral vector; N2C glycoprotein; Neuronal circuits; Retrograde tracing
