Melanopsin activates divergent phototransduction pathways in intrinsically photosensitive retinal ganglion cell subtypes
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.
Metrics
-
- 1,220
- views
-
- 234
- downloads
-
- 4
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
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)
Further reading
-
- Neuroscience
Social relationships guide individual behavior and ultimately shape the fabric of society. Primates exhibit particularly complex, differentiated, and multidimensional social relationships, which form interwoven social networks, reflecting both individual social tendencies and specific dyadic interactions. How the patterns of behavior that underlie these social relationships emerge from moment-to-moment patterns of social information processing remains unclear. Here, we assess social relationships among a group of four monkeys, focusing on aggression, grooming, and proximity. We show that individual differences in social attention vary with individual differences in patterns of general social tendencies and patterns of individual engagement with specific partners. Oxytocin administration altered social attention and its relationship to both social tendencies and dyadic relationships, particularly grooming and aggression. Our findings link the dynamics of visual information sampling to the dynamics of primate social networks.
-
- Neuroscience
As the global population ages, the prevalence of neurodegenerative disorders is fast increasing. This neurodegeneration as well as other central nervous system (CNS) injuries cause permanent disabilities. Thus, generation of new neurons is the rosetta stone in contemporary neuroscience. Glial cells support CNS homeostasis through evolutionary conserved mechanisms. Upon damage, glial cells activate an immune and inflammatory response to clear the injury site from debris and proliferate to restore cell number. This glial regenerative response (GRR) is mediated by the neuropil-associated glia (NG) in Drosophila, equivalent to vertebrate astrocytes, oligodendrocytes (OL), and oligodendrocyte progenitor cells (OPCs). Here, we examine the contribution of NG lineages and the GRR in response to injury. The results indicate that NG exchanges identities between ensheathing glia (EG) and astrocyte-like glia (ALG). Additionally, we found that NG cells undergo transdifferentiation to yield neurons. Moreover, this transdifferentiation increases in injury conditions. Thus, these data demonstrate that glial cells are able to generate new neurons through direct transdifferentiation. The present work makes a fundamental contribution to the CNS regeneration field and describes a new physiological mechanism to generate new neurons.