The Drosophila connectome reveals Axo-Axonic Synapses on Descending Neurons that modulate the Giant Fiber System

Axo-axonic synapses can veto, amplify, or synchronize spikes, yet their circuit-scale logic is unknown. Using the complete electron-microscopy connectome of the adult male Drosophila ventral nerve cord (MANC v1.2.1), we charted every axo-axonic input onto the 1,314 descending neurons that carry brain commands to the ventral nerve cord. Only 1.0 % of the 861,591 possible descending–descending neuron pairs form such contacts, but when present, synaptic strength grows linearly with partner number regardless of transmitter identity. By definition, any synapse connected to a descending neuron within the cord is axo-axonic. Thus, we uncovered the ascending-descending and interneurons-descending axo-axonic relationship. Neurons with many partners (high-degree nodes) integrate into the network without clustering into a densely interconnected ‘rich-club’ of hubs. The connectome identified an octet of ascending neurons (AN08B098) whose axo-axonic input to the Giant Fiber descending neurons (DNp01) predicted modulation of escape control. Immunostaining confirms their cholinergic identity, while optogenetic activation confirmed that this excitatory cohort increases Giant Fiber excitability, validating connectome-derived rules. Our work delivers the first comprehensive map of axo-axonic wiring in a complete ventral nerve cord connectome and constraints for models of fast motor control.