BAcTrace a new tool for retrograde tracing of neuronal circuits

New tools and techniques have enabled many key advances in our understanding of the brain. To elucidate circuit function, it is necessary to identify, record from and manipulate networks of connected neurons. Here we present BAcTrace ( B otulinum Ac tivated Tr acer), the first fully genetically encoded, retrograde, transsynaptic labelling system. BAcTrace is based on C. botulinum neurotoxin A, Botox, which we have engineered to act as a Trojan horse that jumps retrogradely between neurons to activate an otherwise silent transcription factor. We validate BAcTrace at three connections in the Drosophila olfactory system and show that it enables electrophysiological recordings of connected neurons. Finally, in a challenging circuit with highly divergent connections, we used Electron Microscopy connectomics to show that BAcTrace correctly identifies 12 out of 16 connections.