Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping

  1. Kathryn M Tabor
  2. Gregory D Marquart
  3. Christopher Hurt
  4. Trevor S Smith
  5. Alexandra K Geoca
  6. Ashwin A Bhandiwad
  7. Abhignya Subedi
  8. Jennifer L Sinclair
  9. Hannah M Rose
  10. Nicholas F Polys
  11. Harold A Burgess  Is a corresponding author
  1. National Institute of Child Health and Human Development, United States
  2. Virginia Polytechnic Institute and State University, United States

Abstract

Decoding the functional connectivity of the nervous system is facilitated by transgenic methods that express a genetically encoded reporter or effector in specific neurons; however, most transgenic lines show broad spatiotemporal and cell-type expression. Increased specificity can be achieved using intersectional genetic methods which restrict reporter expression to cells that co-express multiple drivers, such as Gal4 and Cre. To facilitate intersectional targeting in zebrafish, we have generated more than 50 new Cre lines, and co-registered brain expression images with the Zebrafish Brain Browser, a cellular resolution atlas of 264 transgenic lines. Lines labeling neurons of interest can be identified using a web-browser to perform a 3D spatial search (zbbrowser.com). This resource facilitates the design of intersectional genetic experiments and will advance a wide range of precision circuit-mapping studies.

Data availability

Registered individual confocal brain scans have been deposited in Dryad https://doi.org/10.5061/dryad.tk467n8

The following data sets were generated

Article and author information

Author details

  1. Kathryn M Tabor

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Gregory D Marquart

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9811-5372
  3. Christopher Hurt

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Trevor S Smith

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Alexandra K Geoca

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Ashwin A Bhandiwad

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Abhignya Subedi

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Jennifer L Sinclair

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Hannah M Rose

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nicholas F Polys

    Department of Computer Science, Virginia Polytechnic Institute and State University, Blacksburg, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Harold A Burgess

    Division of Developmental Biology, National Institute of Child Health and Human Development, Bethesda, United States
    For correspondence
    burgessha@mail.nih.gov
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1966-7801

Funding

Eunice Kennedy Shriver National Institute of Child Health and Human Development (1ZIAHD008884-04)

  • Harold A Burgess

Virginia Tech Advanced Research Computing (NA)

  • Nicholas F Polys

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

Ethics

Animal experimentation: This study was performed in strict accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health. All of the animals were handled according to approved institutional animal care and use committee (IACUC) protocols (#15-039) of the Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Copyright

This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Metrics

  • 5,068
    views
  • 635
    downloads
  • 62
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

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. Kathryn M Tabor
  2. Gregory D Marquart
  3. Christopher Hurt
  4. Trevor S Smith
  5. Alexandra K Geoca
  6. Ashwin A Bhandiwad
  7. Abhignya Subedi
  8. Jennifer L Sinclair
  9. Hannah M Rose
  10. Nicholas F Polys
  11. Harold A Burgess
(2019)
Brain-wide cellular resolution imaging of Cre transgenic zebrafish lines for functional circuit-mapping
eLife 8:e42687.
https://doi.org/10.7554/eLife.42687

Share this article

https://doi.org/10.7554/eLife.42687

Further reading

    1. Neuroscience
    Sara A Nolin, Mary E Faulkner ... Kristina Visscher
    Research Article

    The brain is organized into systems and networks of interacting components. The functional connections among these components give insight into the brain's organization and may underlie some cognitive effects of aging. Examining the relationship between individual differences in brain organization and cognitive function in older adults who have reached oldest old ages with healthy cognition can help us understand how these networks support healthy cognitive aging. We investigated functional network segregation in 146 cognitively healthy participants aged 85+ in the McKnight Brain Aging Registry. We found that the segregation of the association system and the individual networks within the association system [the fronto-parietal network (FPN), cingulo-opercular network (CON) and default mode network (DMN)], has strong associations with overall cognition and processing speed. We also provide a healthy oldest-old (85+) cortical parcellation that can be used in future work in this age group. This study shows that network segregation of the oldest-old brain is closely linked to cognitive performance. This work adds to the growing body of knowledge about differentiation in the aged brain by demonstrating that cognitive ability is associated with differentiated functional networks in very old individuals representing successful cognitive aging.

    1. Cell Biology
    2. Neuroscience
    Vibhavari Aysha Bansal, Jia Min Tan ... Toh Hean Ch'ng
    Research Article

    The emergence of Aβ pathology is one of the hallmarks of Alzheimer’s disease (AD), but the mechanisms and impact of Aβ in progression of the disease is unclear. The nuclear pore complex (NPC) is a multi-protein assembly in mammalian cells that regulates movement of macromolecules across the nuclear envelope; its function is shown to undergo age-dependent decline during normal aging and is also impaired in multiple neurodegenerative disorders. Yet not much is known about the impact of Aβ on NPC function in neurons. Here, we examined NPC and nucleoporin (NUP) distribution and nucleocytoplasmic transport using a mouse model of AD (AppNL-G-F/NL-G-F) that expresses Aβ in young animals. Our studies revealed that a time-dependent accumulation of intracellular Aβ corresponded with a reduction of NPCs and NUPs in the nuclear envelope which resulted in the degradation of the permeability barrier and inefficient segregation of nucleocytoplasmic proteins, and active transport. As a result of the NPC dysfunction App KI neurons become more vulnerable to inflammation-induced necroptosis – a programmed cell death pathway where the core components are activated via phosphorylation through nucleocytoplasmic shutting. Collectively, our data implicates Aβ in progressive impairment of nuclear pore function and further confirms that the protein complex is vulnerable to disruption in various neurodegenerative diseases and is a potential therapeutic target.