Summary

We define the chemoconnectome (CCT) as the entire set of neurotransmitters, neuromodulators, neuropeptides, and their receptors underlying chemotransmission in an animal. We have generated knockout lines of Drosophila CCT genes for functional investigations and knockin lines containing Gal4 and other tools for examining gene expression and manipulating neuronal activities, with a versatile platform allowing genetic intersections and logic gates. CCT reveals the coexistence of specific transmitters but mutual exclusion of the major inhibitory and excitatory transmitters in the same neurons. One neuropeptide and five receptors were detected in glia, with octopamine β2 receptor functioning in glia. A pilot screen implicated 41 genes in sleep regulation, with the dopamine receptor Dop2R functioning in neurons expressing the peptides Dilp2 and SIFa. Thus, CCT is a novel concept, chemoconnectomics a new approach, and CCT tool lines a powerful resource for systematic investigations of chemical-transmission-mediated neural signaling circuits underlying behavior and cognition.