Melanopsin activates divergent phototransduction pathways in intrinsically photosensitive retinal ganglion cell subtypes
- Northwestern University, United States
- 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
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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Melanopsin activates divergent phototransduction pathways in intrinsically photosensitive retinal ganglion cell subtypes
eLife 12:e80749.
https://doi.org/10.7554/eLife.80749
