Quantitative neuroanatomy for connectomics in Drosophila

TLDR

Neuronal circuit mapping with electron microscopy requires laborious proofreading or reconciling multiple independent reconstructions. The study introduces methods that use quantitative arbor and network context to iteratively proofread and reconstruct circuits, producing anatomically enriched wiring diagrams. These methods involve measuring morphological features underlying connectivity in new and existing reconstructions of Drosophila sensorimotor and visual systems, applying quantitative arbor and network context to iteratively proofread and reconstruct circuits. Synaptic inputs cluster on small, microtubule‑free twigs off a microtubule backbone, and omitting individual twigs causes 96 % of errors, but highly connected neurons spread synapses across multiple twigs, making strong connections robust to reconstruction error and allowing iterative reconstruction to replace redundant effort.

Abstract

Neuronal circuit mapping using electron microscopy demands laborious proofreading or reconciliation of multiple independent reconstructions. Here, we describe new methods to apply quantitative arbor and network context to iteratively proofread and reconstruct circuits and create anatomically enriched wiring diagrams. We measured the morphological underpinnings of connectivity in new and existing reconstructions of Drosophila sensorimotor (larva) and visual (adult) systems. Synaptic inputs were preferentially located on numerous small, microtubule-free 'twigs' which branch off a single microtubule-containing 'backbone'. Omission of individual twigs accounted for 96% of errors. However, the synapses of highly connected neurons were distributed across multiple twigs. Thus, the robustness of a strong connection to detailed twig anatomy was associated with robustness to reconstruction error. By comparing iterative reconstruction to the consensus of multiple reconstructions, we show that our method overcomes the need for redundant effort through the discovery and application of relationships between cellular neuroanatomy and synaptic connectivity.