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

Structure and function of the brain are inevitably cross‐linked and knowledge of the finescale morphology and anatomical wiring of neurons give insights into neural circuit function in the healthy brain and defects in brain disorders. Successful neuronal reconstruction requires bright labeling of all neuronal structures (dendrites, spines, axons, boutons) along the entire processes (long‐ranging axons) and permit sparse labeling or visualization by super‐resolution microscopy to be able to distinguish individual processes in the densely packed neuropil. Here we report a novel, pseudotyped anterograde rabies virus that drives high‐level protein expression in bulk or sparse populations of neurons upon infection of their somata, revealing fine‐morphological details within days of infection. Even individual neurons can be targeted in vivo aiding unambiguous high‐resolution and gross‐scale tracing and quantification of their entire axonal arbor in 3D. The novel viral vector complements the existing toolbox for dissecting the structure and function of neuronal circuits