Abstract

Complete wiring diagrams of whole nervous systems will transform neuroscience research. In my lab we aim at obtaining wiring diagrams to generate experimentally testable hypotheses of neural circuit function. At about 150,000 neurons, the wiring diagram of the Drosophila adult fly is beyond reach of current technology. Within the fly model, though, there is second animal: the larva. With only 10,000 neurons, of which about 9600 are identified, stereotyped neurons, and a central nervous system (CNS) that measures, at its smallest, less than 300 μm in length, the larva is an approachable nervous system that embodies the bauplan of the insect brain, with the complete genetic toolkit of the fly. High-throughput behavioral analysis, electrophysiology and calcium imaging are well-established techniques in the larva. Our collaborative web-based approach towards neural circuit reconstruction from large-scale electron microscopy has yielded a draft of 20% of the wiring diagram within the last 18 months. In the context of known circuitry, we are currently studying the function of first-order sensory circuits with normalization motifs across space and modalities, as well as multi-level multi-modal integration pathways that enhance behavioral choice.