# Regulation of the intrinsic melanopsin-based light response in ipRGCs

> **NIH NIH R01** · UNIVERSITY OF MARYLAND BALTIMORE COUNTY · 2024 · $569,691

## Abstract

Abstract
Light has a profound effect on human physiology and behavior. In mammals, intrinsically photosensitive retinal
ganglion cells (ipRGCs) play a key role in light-dependent behaviors, including circadian photoentrainment,
pupillary light reflex, sleep, mood, memory and learning. Originally thought to be a homogeneous population,
ipRGCs are now known to be a diverse collection of cells with six subtypes (M1-6) in mouse. These subtypes
differ in many ways, including expression levels of the photopigment melanopsin, dendritic stratification, synaptic
inputs, firing patterns, and central projection targets in the brain. These ipRGCs respond to light by integrating
intrinsic melanopsin-based phototransduction and extrinsic synaptic inputs driven by conventional rod and cone
outer retinal photoreceptors. Early studies suggested that melanopsin phototransduction utilizes exclusively a
Gq-signaling cascade that leads to the activation of Plc4 and TrpC-family ion channels. This model has been
challenged, however, by discovery of alternative signaling pathways in non-M1 ipRGCs, but the precise identity
of the signaling components remains controversial. These findings have thereby revealed a large gap in
knowledge about the identity of the downstream components of melanopsin’s phototransduction cascade.
Furthermore, we have recently shown that melanopsin signaling can be regulated by dopamine, a well-known
neuromodulator in the retina, in a cell culture system. Our overall goal for this proposal is to understand how the
complexity of the melanopsin-based signaling pathway and its regulation in distinct ipRGC subtypes contributes
to the large array of behaviors. In Specific Aim 1, we will determine the physiological and behavioral
consequences of dopamine-dependent melanopsin phosphorylation in M1 ipRGCs, using a knock-in mouse
model, in which phosphorylation sites in melanopsin are mutated. In Specific Aim 2, we will identify distinct roles
of M1 and M4 ipRGCs in light-dependent behaviors by subtype-selective manipulation of phototransduction
pathways. These studies will provide a critical understanding of the biochemical and molecular mechanisms by
which light influences human health and performance through the regulation of circadian rhythms, sleep, mood,
memory and learning.

## Key facts

- **NIH application ID:** 10832697
- **Project number:** 5R01EY027202-08
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE COUNTY
- **Principal Investigator:** RONALD Lane BROWN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $569,691
- **Award type:** 5
- **Project period:** 2017-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10832697

## Citation

> US National Institutes of Health, RePORTER application 10832697, Regulation of the intrinsic melanopsin-based light response in ipRGCs (5R01EY027202-08). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10832697. Licensed CC0.

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