1. Neuroscience

Circuit mechanisms underlying embryonic retinal waves

  1. Christiane Voufo
  2. Andy Quaen Chen
  3. Benjamin E Smith
  4. Rongshan Yan
  5. Marla B Feller  Is a corresponding author
  6. Alexandre Tiriac  Is a corresponding author
  1. University of California, Berkeley, United States
  2. Vanderbilt University, United States
https://doi.org/10.7554/eLife.81983
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  1. Christiane Voufo
  2. Andy Quaen Chen
  3. Benjamin E Smith
  4. Rongshan Yan
  5. Marla B Feller
  6. Alexandre Tiriac
(2023)
Circuit mechanisms underlying embryonic retinal waves
eLife 12:e81983.
https://doi.org/10.7554/eLife.81983
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Abstract

Spontaneous activity is a hallmark of developing neural systems. In the retina, spontaneous activity comes in the form of retinal waves, comprised of three stages persisting from embryonic day 16 (E16) to eye opening at postnatal day 14 (P14). Though postnatal retinal waves have been well characterized, little is known about the spatiotemporal properties or the mechanisms mediating embryonic retinal waves, designated Stage 1 waves. Using a custom-built macroscope to record spontaneous calcium transients from whole embryonic retinas, we show that Stage 1 waves are initiated at several locations across the retina and propagate across a broad range of areas. Blocking gap junctions reduced the frequency and size of Stage 1 waves, nearly abolishing them. Global blockade of nAChRs similarly nearly abolished Stage 1 waves. Thus, Stage 1 waves are mediated by a complex circuitry involving subtypes of nAChRs and gap junctions. Stage 1 waves in mice lacking the β2 subunit of the nAChRs (β2-nAChR-KO) persisted with altered propagation properties and were abolished by a gap junction blocker. To assay the impact of Stage 1 waves on retinal development, we compared the spatial distribution of a subtype of retinal ganglion cells, intrinsically photosensitive retinal ganglion cells (ipRGCs), which undergo a significant amount of cell death, in WT and β2-nAChR-KO mice. We found that the developmental decrease of ipRGC density is preserved between WT and β2-nAChR-KO mice, indicating that processes regulating ipRGC distribution are not influenced by spontaneous activity.

Data availability

We have uploaded the raw data for Figure 5 on Dryad.All other raw imaging data and images are available upon request as they are too large to update to on Dryad. They are residing on our lab server and can be transferred via ftp.Figures 1-4. These data are based on movies acquired from live imaging of activity using a macroscope or a 2-photon scanning microscope.Figure 1: 50 gigabytesFigures 2/4: 180 gigabytesFigure 3: 233 gigabytesFigure 5: These are high resolution fluorescence images acquired from microscope at various z-plane focus planes. 7 gigabytes total. (on Dryad)All code and software are available in this gitHub location: https://github.com/FellerLabCodeShare/Embryonic-Retinal-WavesInstructions on how to build a macroscope available at this gitHub location: https://github.com/Llamero/DIY_Epifluorescence_Macroscope

The following data sets were generated

Article and author information

Author details

  1. Christiane Voufo

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  2. Andy Quaen Chen

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4970-045X

  3. Benjamin E Smith

    School of Optometry, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  4. Rongshan Yan

    Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, United States
    Competing interests
    No competing interests declared.

  5. Marla B Feller

    Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    mfeller@berkeley.edu
    Competing interests
    Marla B Feller, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9137-5849

  6. Alexandre Tiriac

    Biological Sciences, Vanderbilt University, Nashville, United States
    For correspondence
    alexandre.tiriac@vanderbilt.edu
    Competing interests
    No competing interests declared.

Funding

National Eye Institute (RO1EY013528,RO1EY019498,P30EY003176)

  • Christiane Voufo

National Eye Institute (K99EY030909)

  • Alexandre Tiriac

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

Reviewing Editor

  1. Fred Rieke, University of Washington, United States

Ethics

Animal experimentation: All animal procedures were approved by the UC Berkeley Institutional Animal Care and Use Committee and conformed to the NIH Guide for the Care and Use of Laboratory Animals, the Public Health Service Policy, and the SFN Policy on the Use of Animals in Neuroscience Research.

Version history

  1. Received: July 19, 2022
  2. Preprint posted: August 15, 2022 (view preprint)
  3. Accepted: February 13, 2023
  4. Accepted Manuscript published: February 15, 2023 (version 1)
  5. Version of Record published: March 6, 2023 (version 2)
  6. Version of Record updated: March 15, 2023 (version 3)

Copyright

© 2023, Voufo 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.

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  1. Christiane Voufo
  2. Andy Quaen Chen
  3. Benjamin E Smith
  4. Rongshan Yan
  5. Marla B Feller
  6. Alexandre Tiriac
(2023)
Circuit mechanisms underlying embryonic retinal waves
eLife 12:e81983.
https://doi.org/10.7554/eLife.81983

Share this article

https://doi.org/10.7554/eLife.81983

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