Mapping neural circuits across defined synapses is essential for understanding brain function. Here we describe trans-Tango, a technique for anterograde transsynaptic circuit tracing and manipulation. At the core of trans-Tango is a synthetic signaling pathway that is introduced into all neurons in the animal. This pathway converts receptor activation at the cell surface into reporter expression through site-specific proteolysis. Specific labeling is achieved by presenting a tethered ligand at the synapses of genetically defined neurons, thereby activating the pathway in their postsynaptic partners and providing genetic access to these neurons. We first validated trans-Tango in the Drosophila olfactory system and then implemented it in the gustatory system, where projections beyond the first-order receptor neurons are not fully characterized. We identified putative second-order neurons within the sweet circuit that include projection neurons targeting known neuromodulation centers in the brain. These experiments establish trans-Tango as a flexible platform for transsynaptic circuit analysis. Talay and Richman et al. develop a genetic method for transsynaptic labeling of neural circuits in Drosophila. They validate it in the olfactory system and implement it in the gustatory system to reveal second-order projections of sweet tastant-responsive neurons.
Talay, M., Richman, E. B., Snell, N. J., Hartmann, G. G., Fisher, J. D., Sorkaç, A., … Barnea, G. (2017). Transsynaptic Mapping of Second-Order Taste Neurons in Flies by trans-Tango. Neuron, 96(4), 783-795.e4. https://doi.org/10.1016/j.neuron.2017.10.011