Rabies Virus CVS-N2cΔG Strain Enhances Retrograde Synaptic Transfer and Neuronal Viability

•A new rabies virus strain for monosynaptic circuit mapping and manipulation•Enhanced retrograde transsynaptic transfer•Reduction in neurotoxicity permits optogenetic access to neural circuits

SummaryVirally based transsynaptic tracing technologies are powerful experimental tools for neuronal circuit mapping. The glycoprotein-deletion variant of the SAD-B19 vaccine strain rabies virus (RABV) has been the reagent of choice in monosynaptic tracing, since it permits the mapping of synaptic inputs to genetically marked neurons. Since its introduction, new helper viruses and reagents that facilitate complementation have enhanced the efficiency of SAD-B19ΔG transsynaptic transfer, but there has been little focus on improvements to the core RABV strain. Here we generate a new deletion mutant strain, CVS-N2cΔG, and examine its neuronal toxicity and efficiency in directing retrograde transsynaptic transfer. We find that by comparison with SAD-B19ΔG, the CVS-N2cΔG strain exhibits a reduction in neuronal toxicity and a marked enhancement in transsynaptic neuronal transfer. We conclude that the CVS-N2cΔG strain provides a more effective means of mapping neuronal circuitry and of monitoring and manipulating neuronal activity in vivo in the mammalian CNS.