Melanopsin activates divergent phototransduction pathways in intrinsically photosensitive retinal ganglion cell subtypes

  1. Ely Contreras
  2. Jacob D Bhoi
  3. Takuma Sonoda
  4. Lutz Birnbaumer
  5. Tiffany M Schmidt  Is a corresponding author
  1. Northwestern University, United States
  2. Pontifical Catholic University of Argentina, Argentina

Abstract

Melanopsin signaling within ipRGC subtypes impacts a broad range of behaviors from circadian photoentrainment to conscious visual perception. Yet, how melanopsin phototransduction within M1-M6 ipRGC subtypes impacts cellular signaling to drive diverse behaviors is still largely unresolved. The identity of the phototransduction channels in each subtype is key to understanding this central question but has remained controversial. In this study, we resolve two opposing models of M4 phototransduction, demonstrating that hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are dispensable for this process and providing support for a pathway involving melanopsin-dependent potassium channel closure and canonical transient receptor potential (TRPC) channel opening. Surprisingly, we find that HCN channels are likewise dispensable for M2 phototransduction, contradicting the current model. We instead show that M2 phototransduction requires TRPC channels in conjunction with T-type voltage-gated calcium channels, identifying a novel melanopsin phototransduction target. Collectively, this work resolves key discrepancies in our understanding of ipRGC phototransduction pathways in multiple subtypes and adds to mounting evidence that ipRGC subtypes employ diverse phototransduction cascades to fine-tune cellular responses for downstream behaviors.

Data availability

All data generated are included as individual points and supporting files. Source data files have been provided for all relevant figures.

Article and author information

Author details

  1. Ely Contreras

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3684-5817
  2. Jacob D Bhoi

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Takuma Sonoda

    Department of Neurobiology, Northwestern University, Evanston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Lutz Birnbaumer

    Institute of Biomedical Research, Pontifical Catholic University of Argentina, Buenos Aires, Argentina
    Competing interests
    The authors declare that no competing interests exist.
  5. Tiffany M Schmidt

    Department of Neurobiology, Northwestern University, Evanston, United States
    For correspondence
    tiffany.schmidt@northwestern.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4791-6775

Funding

National Eye Institute (F31EY030360)

  • Takuma Sonoda

National Eye Institute (DP2EY027983)

  • Tiffany M Schmidt

National Eye Institute (R01EY030565)

  • Tiffany M Schmidt

National Eye Institute (T32EY025202)

  • Jacob D Bhoi

National Institutes of Health (Z01-ES-101684)

  • Lutz Birnbaumer

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

Ethics

Animal experimentation: All animals were handled according to approved institutional animal care and use committee of Northwestern University protocol IS00003845.

Copyright

© 2023, Contreras 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. Ely Contreras
  2. Jacob D Bhoi
  3. Takuma Sonoda
  4. Lutz Birnbaumer
  5. Tiffany M Schmidt
(2023)
Melanopsin activates divergent phototransduction pathways in intrinsically photosensitive retinal ganglion cell subtypes
eLife 12:e80749.
https://doi.org/10.7554/eLife.80749

Share this article

https://doi.org/10.7554/eLife.80749

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