# Signal Generation and Processing in the Retinohypothalamic Pathway

> **NIH NIH R01** · BOSTON CHILDREN'S HOSPITAL · 2024 · $696,548

## Abstract

PROJECT SUMMARY
This proposal concerns the broad question of how relevant information is extracted from the environment and
formatted according to animal needs. We focus on the process by which light synchronizes the circadian clock
with the solar day and thus sets appropriate patterns of physiology and gene expression throughout the body.
In mammals, this process requires neurons in the eye that sense light directly using a molecule called
melanopsin and indirectly by receiving input from retinal circuitry. These melanopsin neurons wire into the
principal circadian clock—the suprachiasmatic nucleus of the brain—via the retinohypothalamic pathway. We
have developed new methods of investigating this pathway ex vivo under naturalistic conditions. First is a
means of identifying melanopsin neurons that maintains their maximum photosensitivity (both intrinsic and
extrinsic). Second is an experimental preparation in which the retina and suprachiasmatic nucleus retain
functional connectivity. Using these methods, we will investigate how photic information arises in the retina and
acutely drives neurons of the suprachiasmatic nucleus. We will focus on how this process produces a
representation of the overall light intensity, which reflects the sun’s position in the sky and is used by the clock
to maintain alignment with the day/night cycle. Specifically, we will ask how retinal and suprachiasmatic
circuitry smooth away rapid fluctuations in light intensity, which tend to be uninformative for the clock (being
caused, for example, by a passing cloud or flash of lightning). We expect that this work will provide knowledge
of how neural processing is tailored to specific tasks and how environmental cues interact with internal states
according to animal needs.

## Key facts

- **NIH application ID:** 10858461
- **Project number:** 1R01EY036071-01
- **Recipient organization:** BOSTON CHILDREN'S HOSPITAL
- **Principal Investigator:** Michael Tri Hoang Do
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $696,548
- **Award type:** 1
- **Project period:** 2024-05-01 → 2029-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10858461

## Citation

> US National Institutes of Health, RePORTER application 10858461, Signal Generation and Processing in the Retinohypothalamic Pathway (1R01EY036071-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10858461. Licensed CC0.

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