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).

Reviewing Editor

  1. Teresa Giraldez, Universidad de La Laguna, Spain

Publication history

  1. Received: August 17, 2020
  2. Accepted: September 9, 2020
  3. Accepted Manuscript published: September 17, 2020 (version 1)
  4. Version of Record published: October 15, 2020 (version 2)

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

  • 1,419
    Page views
  • 257
    Downloads
  • 8
    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. 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

Further reading

    1. Neuroscience
    Stefanie Engert et al.
    Research Article

    Gustatory sensory neurons detect caloric and harmful compounds in potential food and convey this information to the brain to inform feeding decisions. To examine the signals that gustatory neurons transmit and receive, we reconstructed gustatory axons and their synaptic sites in the adult Drosophila melanogaster brain, utilizing a whole-brain electron microscopy volume. We reconstructed 87 gustatory projections from the proboscis labellum in the right hemisphere and 57 from the left, representing the majority of labellar gustatory axons. Gustatory neurons contain a nearly equal number of interspersed pre-and post-synaptic sites, with extensive synaptic connectivity among gustatory axons. Morphology- and connectivity-based clustering revealed six distinct groups, likely representing neurons recognizing different taste modalities. The vast majority of synaptic connections are between neurons of the same group. This study resolves the anatomy of labellar gustatory projections, reveals that gustatory projections are segregated based on taste modality, and uncovers synaptic connections that may alter the transmission of gustatory signals.

    1. Neuroscience
    Vladislav Ayzenberg, Stella Lourenco
    Research Article

    Categorization of everyday objects requires that humans form representations of shape that are tolerant to variations among exemplars. Yet, how such invariant shape representations develop remains poorly understood. By comparing human infants (6–12 months; N=82) to computational models of vision using comparable procedures, we shed light on the origins and mechanisms underlying object perception. Following habituation to a never-before-seen object, infants classified other novel objects across variations in their component parts. Comparisons to several computational models of vision, including models of high-level and low-level vision, revealed that infants’ performance was best described by a model of shape based on the skeletal structure. Interestingly, infants outperformed a range of artificial neural network models, selected for their massive object experience and biological plausibility, under the same conditions. Altogether, these findings suggest that robust representations of shape can be formed with little language or object experience by relying on the perceptually invariant skeletal structure.