In the mammalian retina, there is a small subset of retinal ganglion cells (RGCs) that function as autonomous photoreceptors and exhibit light responses independent of rod/cone-driven synaptic input. These intrinsically photosensitive RGCs (known as, ipRGCs) relay light information to the brain to regulate several light-dependent processes, such as circadian photoentrainment, the pupillary light reflex (PLR), sleep, and mood. ipRGCs use the photopigment melanopsin and a G-protein coupled phototransduction cascade to respond to light, and are now known to comprise 5 different subtypes (M1-5) that can be differentiated based on morphological and electrophysiological criteria, projection targets, and transcription factor expression. Currently, there exists a major gap in our understanding of how the regulation of melanopsin and its downstream phototransduction pathways in different ipRGC subtypes govern distinct light-mediated behaviors. Based on our preliminary data, the goal of the proposed research is to determine, in Aim I, the role of melanopsin posttranslational modifications in ipRGC-mediated behaviors in vivo, and in Aim II, the phototransduction components that allow distinct ipRGC subtypes to intrinsically detect light and influence ipRGC-subtype specific behaviors. These studies will provide a critical understanding of the biochemical and molecular mechanisms by which light influences a wide range effects on human health and performance through the regulation of circadian rhythms, sleep, mood, and learning & memory.

Public Health Relevance

The intrinsically photosensitive retinal ganglion cells (ipRGCs) are recently identified photoreceptors in the mammalian eye that regulate fundamental light-mediated behaviors, including the pupillary light reflex, circadian rhythms, sleep, mood and learning & memory. The goal of this proposal is to understand how the phototransduction pathway in ipRGCs, including regulation of the photopigment melanopsin, controls light- mediated behaviors in vivo. These studies are essential to understand a visual system that has wide range effects on human health through the regulation of circadian rhythms, sleep, mood, and learning & memory.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY027202-01A1
Application #
9263558
Study Section
Biology of the Visual System Study Section (BVS)
Program Officer
Greenwell, Thomas
Project Start
2017-05-01
Project End
2022-04-30
Budget Start
2017-05-01
Budget End
2018-04-30
Support Year
1
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21205
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