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

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

Version 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

  • 6,091
    Page views
  • 610
    Downloads
  • 13
    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)

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

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

  1. Justin W Kenney
  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
(2021)
A 3D adult zebrafish brain atlas (AZBA) for the digital age
eLife 10:e69988.
https://doi.org/10.7554/eLife.69988

Share this article

https://doi.org/10.7554/eLife.69988

Further reading

    1. Neuroscience
    Maureen van der Grinten, Jaap de Ruyter van Steveninck ... Yağmur Güçlütürk
    Tools and Resources

    Blindness affects millions of people around the world. A promising solution to restoring a form of vision for some individuals are cortical visual prostheses, which bypass part of the impaired visual pathway by converting camera input to electrical stimulation of the visual system. The artificially induced visual percept (a pattern of localized light flashes, or ‘phosphenes’) has limited resolution, and a great portion of the field’s research is devoted to optimizing the efficacy, efficiency, and practical usefulness of the encoding of visual information. A commonly exploited method is non-invasive functional evaluation in sighted subjects or with computational models by using simulated prosthetic vision (SPV) pipelines. An important challenge in this approach is to balance enhanced perceptual realism, biologically plausibility, and real-time performance in the simulation of cortical prosthetic vision. We present a biologically plausible, PyTorch-based phosphene simulator that can run in real-time and uses differentiable operations to allow for gradient-based computational optimization of phosphene encoding models. The simulator integrates a wide range of clinical results with neurophysiological evidence in humans and non-human primates. The pipeline includes a model of the retinotopic organization and cortical magnification of the visual cortex. Moreover, the quantitative effects of stimulation parameters and temporal dynamics on phosphene characteristics are incorporated. Our results demonstrate the simulator’s suitability for both computational applications such as end-to-end deep learning-based prosthetic vision optimization as well as behavioral experiments. The modular and open-source software provides a flexible simulation framework for computational, clinical, and behavioral neuroscientists working on visual neuroprosthetics.

    1. Neuroscience
    Simon Lui, Ashleigh K Brink, Laura H Corbit
    Research Article

    Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies.