Learning Neuronal Wiring Rules from Morphological Token Sequences

Does a neuron’s shape predict whom it connects to? Peters’ rule, a canonical geo- metric principle in connectomics, predicts connectivity from spatial arbor overlap, but true wiring also depends on molecular and morphological specificity. We ask how far neuron skeletons, with identity and graph features withheld, predict directed connections in the FlyWire Drosophila connectome. Because most non- connected pairs are far apart, headline metrics are dominated by easy negatives that geometry can reject. We therefore evaluate controlled contrasts: plausible non-connections whose arbors are nearby, overlapping, or cell-type matched, but that still do not synapse. Across a controlled model ladder, from arbor overlap and hand-crafted morphology baselines to Connectoformer (a bidirectional Trans- former with pooled and pairwise cross-attention scoring), performance improves when the model gains the corresponding signal: global shape, local branch com- patibility, and tree context. Morphology and arbor co-occupancy are complemen- tary: morphology discriminates similar-looking unconnected pairs but can score pairs whose arbors never touch; arbor co-occupancy does the inverse. By suppress- ing essentially-zero-overlap pairs without boosting high-overlap pairs, a fixed one- sided arbor prior performs well in both regimes. The encoder also transfers across Drosophila individuals: zero-shot evaluation on the male CNS connectome beats arbor overlap on hard-negative discrimination. Stratified evaluation reveals a clean division of labor: geometry rules out pairs that cannot physically connect, and morphology picks the actual partners from what remains.