Uncovering Sex Differences in the Drosophila Ventral Nerve Cord Through Connectome Alignment

There are now multiple Drosophila connectomes available, comprising both its brain and spinal cord - comparing these connectomes requires first classifying neurons into cell types. Existing approaches for cell typing typically require extensive manual curation. Here we present a new method that automatically aligns connectomes via network topology alone. Using two complete male ventral nerve cord (VNC) connectomes as references, we assign cell types to ~13,000 neurons intrinsic to the female VNC, and automatically identify sex-specific and sexually dimorphic cell types. We not only provide a comprehensive census of cell types across male and female nerve cords, but we uncover connectivity differences that underlie differences in function. We focus on circuits underlying song production in males and oviposition behaviors in females, and investigate the counterparts of these circuits across sexes. Our automated methods and analyses provide insights into sex differences in circuits that connect the brain and body, and pave the way for comparative connectomics at scale.