A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction

  1. William Thomas Keenan
  2. Alan C Rupp
  3. Rachel A Ross
  4. Preethi Somasundaram
  5. Suja Hiriyanna
  6. Zhijian Wu
  7. Tudor C Badea
  8. Phyllis R Robinson
  9. Bradford B Lowell
  10. Samer S Hattar  Is a corresponding author
  1. Johns Hopkins University, United States
  2. Beth Israel Deaconess Medical Center, United States
  3. University of Marlyand, United States
  4. National Institutes of Health, United States
  5. Harvard Medical School, United States

Abstract

Rapid and stable control of pupil size in response to light is critical for vision, but the neural coding mechanisms remain unclear. Here, we investigated the neural basis of pupil control by monitoring pupil size across time while manipulating each photoreceptor input or neurotransmitter output of intrinsically photosensitive retinal ganglion cells (ipRGCs), a critical relay in the control of pupil size. We show that transient and sustained pupil responses are mediated by distinct photoreceptors and neurotransmitters. Transient responses utilize input from rod photoreceptors and output by the classical neurotransmitter glutamate , but adapt within minutes. In contrast, sustained responses are dominated by non-conventional signaling mechanisms: melanopsin phototransduction in ipRGCs and output by the neuropeptide PACAP, which provide stable pupil maintenance across the day. These results highlight a temporal switch in the coding mechanisms of a neural circuit to support proper behavioral dynamics.

Article and author information

Author details

  1. William Thomas Keenan

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3381-744X
  2. Alan C Rupp

    Department of Biology, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Rachel A Ross

    Department of Psychiatry, Beth Israel Deaconess Medical Center, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Preethi Somasundaram

    Department of Biological Sciences, University of Marlyand, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Suja Hiriyanna

    National Eye Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Zhijian Wu

    National Eye Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Tudor C Badea

    National Eye Institute, National Institutes of Health, Bethesda, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Phyllis R Robinson

    Department of Biological Sciences, University of Marlyand, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Bradford B Lowell

    Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Samer S Hattar

    Department of Biology, Johns Hopkins University, Baltimore, United States
    For correspondence
    shattar@jhu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3124-9525

Funding

National Eye Institute (R21)

  • William Thomas Keenan
  • Alan C Rupp
  • Samer S Hattar

National Institute of General Medical Sciences (RO1)

  • William Thomas Keenan
  • Alan C Rupp
  • Samer S Hattar

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 mice were housed according to guidelines from the Animal Care and Use Committee of Johns Hopkins University (Protocol # MO16A212), and used protocols approved by the JHU animal care and use committee.

Reviewing Editor

  1. Constance L Cepko, Howard Hughes Medical Institute, Harvard Medical School, United States

Publication history

  1. Received: February 19, 2016
  2. Accepted: September 22, 2016
  3. Accepted Manuscript published: September 26, 2016 (version 1)
  4. Accepted Manuscript updated: October 7, 2016 (version 2)
  5. Version of Record published: October 25, 2016 (version 3)

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.

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  1. William Thomas Keenan
  2. Alan C Rupp
  3. Rachel A Ross
  4. Preethi Somasundaram
  5. Suja Hiriyanna
  6. Zhijian Wu
  7. Tudor C Badea
  8. Phyllis R Robinson
  9. Bradford B Lowell
  10. Samer S Hattar
(2016)
A visual circuit uses complementary mechanisms to support transient and sustained pupil constriction
eLife 5:e15392.
https://doi.org/10.7554/eLife.15392
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