New Synapse Detection in the Whole-Brain Connectome of Drosophila

The FlyWire Drosophila brain connectome 1 is a graph of roughly 140K neurons and >50 million synaptic connections 2,3 reconstructed from the FAFB EM dataset 4 . Challenges in synapse detection were identified for neurons with features such as dark cytosols, axo-axonic synapses, and complex polyadic synapses, due to limitations in ground truth data for these cells and the inherent complexity of these synapse types. To address these issues, we trained new neural networks using iteratively generated ground truth annotations and detected synapses across the entire FAFB dataset, producing what we refer to here as the ‘Princeton synapses.’ These synapses were evaluated in both control regions, such as subareas of the mushroom body calyx and lateral horn, which were also chosen by Buhmann et al. 3 for evaluation, as well as challenging regions, including Johnston’s Organ neurons (JONs), photoreceptors, and other cell types. The new model shows significant improvements, achieving up to a 0.23 F-score increase in challenging areas, while maintaining performance in control regions. Princeton synapses also show an 8–9% improvement in neuron clustering within cell types and better left/right symmetry scores, especially for photoreceptors. Additionally, neuron type membership can be predicted from connectivity patterns alone with weighted F-scores of 0.93 for Princeton synapses versus 0.91 for Buhmann synapses. The updated Princeton synapses are now accessible via Codex (codex.flywire.ai).