A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse

  1. J Wesley Maddox
  2. Kate L Randall
  3. Ravi P Yadav
  4. Brittany Williams
  5. Jussara Hagen
  6. Paul J Derr
  7. Vasily Kerov
  8. Luca Della Santina
  9. Sheila A Baker
  10. Nikolai Artemyev
  11. Mrinalini Hoon
  12. Amy Lee  Is a corresponding author
  1. University of Iowa, United States
  2. University of Wisconsin, Madison, United States
  3. University of California, San Francisco, United States
  4. University of Iowa Carver College of Medicine, United States

Abstract

Synapses are fundamental information processing units that rely on voltage-gated Ca2+ (Cav) channels to trigger Ca2+-dependent neurotransmitter release. Cav channels also play Ca2+-independent roles in other biological contexts, but whether they do so in axon terminals is unknown. Here, we addressed this unknown with respect to the requirement for Cav1.4 L-type channels for the formation of rod photoreceptor synapses in the retina. Using a mouse strain expressing a non-conducting mutant form of Cav1.4, we report that the Cav1.4 protein, but not its Ca2+ conductance, is required for the molecular assembly of rod synapses; however, Cav1.4 Ca2+ signals are needed for the appropriate recruitment of postsynaptic partners. Our results support a model in which presynaptic Cav channels serve both as organizers of synaptic building blocks and as sources of Ca2+ ions in building the first synapse of the visual pathway and perhaps more broadly in the nervous system.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. J Wesley Maddox

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Kate L Randall

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ravi P Yadav

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Brittany Williams

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Jussara Hagen

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Paul J Derr

    Neuroscience, University of Wisconsin, Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Vasily Kerov

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Luca Della Santina

    Department of Ophthalmology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Sheila A Baker

    Biochemistry, University of Iowa, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Nikolai Artemyev

    Molecular Physiology, University of Iowa Carver College of Medicine, Iowa City, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Mrinalini Hoon

    Department of Neuroscience, University of Wisconsin, Madison, Madison, United States
    Competing interests
    The authors declare that no competing interests exist.
  12. Amy Lee

    Molecular Physiology and Biophysics, University of Iowa, Iowa City, United States
    For correspondence
    amy-lee@uiowa.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8021-0443

Funding

National Eye Institute (EY 026817)

  • Amy Lee

McPherson Eye Research Institute

  • Mrinalini Hoon

Research to Prevent Blindness

  • Mrinalini Hoon

National Eye Institute (EY 029953)

  • J Wesley Maddox

National Eye Institute (EY 026477)

  • Brittany Williams

National Eye Institute (EY010843,EY012682)

  • Nikolai Artemyev

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 (#7121262-025) of the University of Iowa. The protocol was approved by the Office of Institutional Animal Care and Use Committee of the University of Iowa (A3021-01).

Copyright

© 2020, Maddox 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

  • 2,226
    views
  • 368
    downloads
  • 31
    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. J Wesley Maddox
  2. Kate L Randall
  3. Ravi P Yadav
  4. Brittany Williams
  5. Jussara Hagen
  6. Paul J Derr
  7. Vasily Kerov
  8. Luca Della Santina
  9. Sheila A Baker
  10. Nikolai Artemyev
  11. Mrinalini Hoon
  12. Amy Lee
(2020)
A dual role for Cav1.4 Ca2+ channels in the molecular and structural organization of the rod photoreceptor synapse
eLife 9:e62184.
https://doi.org/10.7554/eLife.62184

Share this article

https://doi.org/10.7554/eLife.62184

Further reading

    1. Neuroscience
    Friedrich Schuessler, Francesca Mastrogiuseppe ... Omri Barak
    Research Article

    The relation between neural activity and behaviorally relevant variables is at the heart of neuroscience research. When strong, this relation is termed a neural representation. There is increasing evidence, however, for partial dissociations between activity in an area and relevant external variables. While many explanations have been proposed, a theoretical framework for the relationship between external and internal variables is lacking. Here, we utilize recurrent neural networks (RNNs) to explore the question of when and how neural dynamics and the network’s output are related from a geometrical point of view. We find that training RNNs can lead to two dynamical regimes: dynamics can either be aligned with the directions that generate output variables, or oblique to them. We show that the choice of readout weight magnitude before training can serve as a control knob between the regimes, similar to recent findings in feedforward networks. These regimes are functionally distinct. Oblique networks are more heterogeneous and suppress noise in their output directions. They are furthermore more robust to perturbations along the output directions. Crucially, the oblique regime is specific to recurrent (but not feedforward) networks, arising from dynamical stability considerations. Finally, we show that tendencies toward the aligned or the oblique regime can be dissociated in neural recordings. Altogether, our results open a new perspective for interpreting neural activity by relating network dynamics and their output.

    1. Neuroscience
    Sudhanvan Iyer, Kathryn Maxson Jones ... Mary A Majumder
    Review Article

    In this paper, we provide an overview and analysis of the BRAIN Initiative data-sharing ecosystem. First, we compare and contrast the characteristics of the seven BRAIN Initiative data archives germane to data sharing and reuse, namely data submission and access procedures and aspects of interoperability. Second, we discuss challenges, benefits, and future opportunities, focusing on issues largely specific to sharing human data and drawing on N = 34 interviews with diverse stakeholders. The BRAIN Initiative-funded archive ecosystem faces interoperability and data stewardship challenges, such as achieving and maintaining interoperability of data and archives and harmonizing research participants’ informed consents for tiers of access for human data across multiple archives. Yet, a benefit of this distributed archive ecosystem is the ability of more specialized archives to adapt to the needs of particular research communities. Finally, the multiple archives offer ample raw material for network evolution in response to the needs of neuroscientists over time. Our first objective in this paper is to provide a guide to the BRAIN Initiative data-sharing ecosystem for readers interested in sharing and reusing neuroscience data. Second, our analysis supports the development of empirically informed policy and practice aimed at making neuroscience data more findable, accessible, interoperable, and reusable.