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

Researchers from the Max Planck Institute for Biological Intelligence, Google Inc. and the Paul Scherrer Institute published a new method and data resource that makes connectomic analyses of the entire larval zebrafish brain possible. The scientists identified approximately 121,000 neurons and their synaptic connections by combining serial block-face electron microscopy (SBEM) with automated segmentation and synapse detection. The easy-to-use computational framework and data resource will enable the research community to study the neuronal networks in the zebrafish brain at unprecedented detail.

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.