Automated synapse-level reconstruction of neural circuits in the larval zebrafish brain
Open accessAbstract
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 nm 3. 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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In vertebrate EM datasets, human annotators can see differences in the vesicles for excitatory and inhibitory synapses.
“In vertebrate EM datasets, human annotators can see differences in the vesicles for excitatory and inhibitory synapses.16,35,36,37,109,110”
From Neurotransmitter classification from electron microscopy images at synaptic sites in Drosophila melanogaster (2024) · cites this paper as [16]
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- Authors
- Svara, F., Förster, D., Kubo, F., Januszewski, M., dal Maschio, M., Schubert, P. J., Kornfeld, J., Wanner, A. A., Laurell, E., Denk, W., & Baier, H.
- Affiliations
- Max Planck Institute for Neurobiology of Behavior – caesar (DE)
- University of Cologne (DE)
- National Institute of Genetics (JP)
- Google (Switzerland) (CH)
- Max Planck Institute for Biological Intelligence (DE)
- Princeton University (US)
- Corresponding author
- Baier, Herwig
- ORCID
- Venue
- Nature Methods
- Published
- 2022-10-24
- Volume
- 19
- Issue
- 11
- Pages
- 1357-1366
- ISSN
- 1548-7091 (ISSN-L)
- 1548-7105
- PMC
- PMC9636024
- OpenAlex
- W4307231400
- Cited by
- 124
- References
- 62
- Citations by year
- 2026: 22 · 2025: 41 · 2024: 31 · 2023: 25 · 2022: 4 · 2020: 1
- FWCI
- 12.58
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Methods (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- DORA PSI (Paul Scherrer Institute) (submittedVersion, other-oa)
- Padua Research Archive (University of Padova) (submittedVersion, cc-by)
- Funders
- Max-Planck-Gesellschaft
- Deutsche Forschungsgemeinschaft (SFB 870/TP16, SPP2041)
- European Molecular Biology Organization
- Boehringer Ingelheim Fonds
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Zebrafish Biomedical Research Applications
- Keywords
- serial block-face electron microscopy, visual motion processing, pretectum
- MeSH terms
- Animals, Brain, Larva, Microscopy, Electron, Synapses, Zebrafish
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