Connectome studies on Drosophila: a short perspective on a tiny brain

The brain is a network of neurons, one that generates behaviour, and knowing the former is crucial to understanding the latter. Identifying the exact network of synaptic connections, or connectome, of the fly's central nervous system is now a major objective in Drosophila neurobiology, one that has been initiated in several laboratories, especially the Janelia Research Campus of the Howard Hughes Medical Institute. Progress is most advanced in the optic neuropiles of the visual system. The effort to derive a connectome from these and other neuropile regions is proceeding by various methods of electron microscopy, especially focused-ion beam milling scanning electron microscopy, and relies upon - but is to be carefully distinguished from - published light microscopic methods that reveal the projections of genetically labelled cell types. The latter reveal those neurons that come into close proximity and are therefore candidate synaptic partners. Synaptic partnerships are not in fact reliably revealed by such candidate pairs, anatomical connections often revealing unexpected pathways. Synaptic partnerships identified from ultrastructural features provide a strong heuristic basis to interpret not only functional interactions between identified neurons, but also a powerful means to predict such interactions, and suggest functional pathways not readily predicted from existing experimental evidence. The analysis of circuit function may proceed cell by cell, by examining the behavioural outcome of either interrupting or restoring function to any one element in an anatomically defined circuit, but can be foiled by degeneracy in pathway elements. Circuit information can also be used to identify and analyse circuit motifs, and their role in higher-order network properties. These attempts in Drosophila anticipate parallel attempts in other systems, notably the inner plexiform layer of the vertebrate retina, and augment the one complete connectome already available to us, that available for 30 years in the nematode Caenorhabditis elegans.