1. Neuroscience
Download icon

A 3D adult zebrafish brain atlas (AZBA) for the digital age

  1. Justin W Kenney  Is a corresponding author
  2. Patrick E Steadman
  3. Olivia Young
  4. Meng Ting Shi
  5. Maris Polanco
  6. Saba Dubaishi
  7. Kristopher Covert
  8. Thomas Mueller
  9. Paul W Frankland  Is a corresponding author
  1. Wayne State University, United States
  2. The Hospital for Sick Children, Canada
  3. Kansas State University, United States
  4. University of Toronto, Canada
Tools and Resources
  • Cited 0
  • Views 1,252
  • Annotations
Cite this article as: eLife 2021;10:e69988 doi: 10.7554/eLife.69988

Abstract

Zebrafish have made significant contributions to our understanding of the vertebrate brain and the neural basis of behavior, earning a place as one of the most widely used model organisms in neuroscience. Their appeal arises from the marriage of low cost, early life transparency, and ease of genetic manipulation with a behavioral repertoire that becomes more sophisticated as animals transition from larvae to adults. To further enhance the use of adult zebrafish, we created the first fully segmented three-dimensional digital adult zebrafish brain atlas (AZBA). AZBA was built by combining tissue clearing, light-sheet fluorescence microscopy, and three-dimensional image registration of nuclear and antibody stains. These images were used to guide segmentation of the atlas into over 200 neuroanatomical regions comprising the entirety of the adult zebrafish brain. As an open source, online (azba.wayne.edu), updatable digital resource, AZBA will significantly enhance the use of adult zebrafish in furthering our understanding of vertebrate brain function in both health and disease.

Data availability

Data have been deposited in Dryad, accessible at: https://doi.org/10.5061/dryad.dfn2z351g

The following data sets were generated

Article and author information

Author details

  1. Justin W Kenney

    Department of Biological Sciences, Wayne State University, Detroit, United States
    For correspondence
    jkenney9@wayne.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8790-5184
  2. Patrick E Steadman

    The Hospital for Sick Children, Toronto, Canada
    Competing interests
    The authors declare that no competing interests exist.
  3. Olivia Young

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Meng Ting Shi

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Maris Polanco

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Saba Dubaishi

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Kristopher Covert

    Department of Biological Sciences, Wayne State University, Detroit, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Thomas Mueller

    Kansas State University, Manhattan, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Paul W Frankland

    Department of Physiology, University of Toronto, Toronto, Canada
    For correspondence
    paul.frankland@sickkids.ca
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1395-3586

Funding

Human Frontiers Science Program (LT000759/2014)

  • Justin W Kenney

National Institutes of Health (R35GM142566)

  • Justin W Kenney

Canadian Institute for Health Research (FDN143227)

  • Paul W Frankland

National Institutes of Health (P20GM113109)

  • Thomas Mueller

Human Frontiers Science Program (RGP0016/2019)

  • Thomas Mueller

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: The study was performed in accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All procedures were approved by the animal care committee of The Hospital for Sick Children (protocol #0000047792).

Reviewing Editor

  1. Stephen C Ekker, Mayo Clinic, United States

Publication history

  1. Received: May 3, 2021
  2. Accepted: November 21, 2021
  3. Accepted Manuscript published: November 22, 2021 (version 1)
  4. Version of Record published: December 2, 2021 (version 2)

Copyright

© 2021, Kenney et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

Metrics

  • 1,252
    Page views
  • 205
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

  1. Further reading

Further reading

    1. Computational and Systems Biology
    2. Neuroscience
    Ling-Qi Zhang et al.
    Research Article

    We developed an image-computable observer model of the initial visual encoding that operates on natural image input, based on the framework of Bayesian image reconstruction from the excitations of the retinal cone mosaic. Our model extends previous work on ideal observer analysis and evaluation of performance beyond psychophysical discrimination, takes into account the statistical regularities of the visual environment, and provides a unifying framework for answering a wide range of questions regarding the visual front end. Using the error in the reconstructions as a metric, we analyzed variations of the number of different photoreceptor types on human retina as an optimal design problem. In addition, the reconstructions allow both visualization and quantification of information loss due to physiological optics and cone mosaic sampling, and how these vary with eccentricity. Furthermore, in simulations of color deficiencies and interferometric experiments, we found that the reconstructed images provide a reasonable proxy for modeling subjects' percepts. Lastly, we used the reconstruction-based observer for the analysis of psychophysical threshold, and found notable interactions between spatial frequency and chromatic direction in the resulting spatial contrast sensitivity function. Our method is widely applicable to experiments and applications in which the initial visual encoding plays an important role.

    1. Neuroscience
    Casey M Schneider-Mizell et al.
    Research Article Updated

    Inhibitory neurons in mammalian cortex exhibit diverse physiological, morphological, molecular, and connectivity signatures. While considerable work has measured the average connectivity of several interneuron classes, there remains a fundamental lack of understanding of the connectivity distribution of distinct inhibitory cell types with synaptic resolution, how it relates to properties of target cells, and how it affects function. Here, we used large-scale electron microscopy and functional imaging to address these questions for chandelier cells in layer 2/3 of the mouse visual cortex. With dense reconstructions from electron microscopy, we mapped the complete chandelier input onto 153 pyramidal neurons. We found that synapse number is highly variable across the population and is correlated with several structural features of the target neuron. This variability in the number of axo-axonic ChC synapses is higher than the variability seen in perisomatic inhibition. Biophysical simulations show that the observed pattern of axo-axonic inhibition is particularly effective in controlling excitatory output when excitation and inhibition are co-active. Finally, we measured chandelier cell activity in awake animals using a cell-type-specific calcium imaging approach and saw highly correlated activity across chandelier cells. In the same experiments, in vivo chandelier population activity correlated with pupil dilation, a proxy for arousal. Together, these results suggest that chandelier cells provide a circuit-wide signal whose strength is adjusted relative to the properties of target neurons.