Rabies Virus Pseudotyped with CVS-N2C Glycoprotein as a Powerful Tool for Retrograde Neuronal Network Tracing

Neurosci Bull. 2020 Mar;36(3):202-216. doi: 10.1007/s12264-019-00423-3. Epub 2019 Aug 23.

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: N2C glycoprotein; Neuronal circuits; Retrograde tracing; Viral vector.

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Dentate Gyrus*
  • Genetic Vectors*
  • Glycoproteins*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Net*
  • Neuroanatomical Tract-Tracing Techniques*
  • Rabies virus*
  • Ventral Tegmental Area*
  • Viral Proteins*

Substances

  • Glycoproteins
  • Viral Proteins