ORIGINAL ARTICLE An anterograde rabies virus vector for high-resolution large-scale reconstruction of 3D neuron morphology

Abstract Glycoprotein-deleted rabies virus (RABV DG) is a powerful tool for the analysis of neural circuits. Here, we demonstrate the utility of an anterograde RABV DG variant for novel neuroanatomical approaches involving either bulk or sparse neuronal populations. This technology exploits the unique features of RABV DG vectors, namely autonomous, rapid high-level expression of transgenes, and limited cytotoxicity. Our vector permits the unambiguous long-range and fine-scale tracing of the entire axonal arbor of individual neurons throughout the brain. Notably, this level of labeling can be achieved following infection with a single viral particle. The vector is effective over a range of ages ([14 months) aiding the studies of neurodegenerative disorders or aging, and infects numerous cell types in all brain regions tested. Lastly, it can also be readily combined with retrograde RABV DG variants. Together with other modern technologies, this tool provides new possibilities for the investigation of the anatomy and physiology of neural circuits