Genetically engineered rabies virus is a powerful tool for investigating the structure and function of neural circuits because of its directional trans-synaptic spreading6,7. Most rabies virus tools were derived from the SAD B19 vaccine strain. Their applications have been limited to short-term experiments because of rabies-induced cytotoxicity. Rabies-induced changes in host cell gene expression also complicate molecular identification of the infected cell types within traced neural circuits8. Lee et al. generated a self-inactivating rabies virus (SiR) using the parent strain CVS N2c, ultimately generating the SiR-N2c viral strain5. They report this strain allows long-term circuit mapping owing to reduced cytotoxicity, reduced immune responses and minimal gene expression changes, enabling single-cell transcriptomics of rabies-traced neurons.
