Path knockout: an analysis tool for connectome-driven circuit discovery

Path knockout identifies dominant multi-synaptic pathways in Drosophila connectomes by computing connection strength from synapse input fractions and ranking interneurons by removal impact.

• Why it matters: Connectome-scale wiring makes it hard to extract functionally relevant multi-synaptic routes between neuron populations, limiting connectome-driven circuit discovery.
• What they did: The method estimates the approximate probability that at least one multi-synaptic path succeeds between defined sources and sinks, then measures each interneuron’s importance by how its removal changes connection strength.
• The result: In Drosophila circuits, path knockout outperforms other pathway-analysis methods, finds known and novel interneurons, and reveals a convergent motif linking sexually dimorphic aggression command neurons to a shared visual pursuit pathway.

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