Google Research

Automated synapse-level reconstruction of neural circuits in the larval zebrafish brain

  • Fabian Svara
  • Dominique Förster
  • Fumi Kubo
  • Michal Januszewski
  • Marco dal Maschio
  • Philipp Schubert
  • Jörgen Kornfeld
  • Adrian Wanner
  • Winfried Denk
  • Herwig Baier
Nature Methods, vol. 19 (2022), 1357–1366


Dense reconstruction of synaptic connectivity requires high-resolution electron microscopy images of entire brains and tools to efficiently trace neuronal wires across the volume. To generate such a resource, we sectioned and imaged a larval zebrafish brain by serial block-face electron microscopy at a voxel size of 14 × 14 × 25 nm3. We segmented the resulting dataset with the flood-filling network algorithm, automated the detection of chemical synapses and validated the results by comparisons to transmission electron microscopic images and light-microscopic reconstructions. Neurons and their connections are stored in the form of a queryable and expandable digital address book. We reconstructed a network of 208 neurons involved in visual motion processing, most of them located in the pretectum, which had been functionally characterized in the same specimen by two-photon calcium imaging. Moreover, we mapped all 407 presynaptic and postsynaptic partners of two superficial interneurons in the tectum. The resource developed here serves as a foundation for synaptic-resolution circuit analyses in the zebrafish nervous system.

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