Jagadish, S. et al. Neuron 83, 630–644 (2014).

Though anterograde and retrograde tracers are useful for characterizing functional synaptic connections, such tracers are not available for the Drosophila nervous system. Jagadish et al. describe an alternative strategy to identify neurons postsynaptic to Drosophila photoreceptors. The histamine release from photoreceptors results in the activation in postsynaptic cells of an ectopically expressed histamine receptor, which is fused to the transcriptional activator Gal4. This activation in turn leads to the recruitment of another ectopically expressed protein, a fusion between arrestin and a tobacco etch virus protease. Upon interaction of the histamine receptor and the arrestin fusion proteins, Gal4 is released and can induce the transcription of a marker such as GFP. Thus, this strategy fluorescently labels neurons downstream of the histaminergic photoreceptors. The system may be adapted to other neurotransmitters.