Divergent molecular and circuit mechanisms underlie light entrainment of retinal and suprachiasmatic nucleus circadian clocks
Abstract
The circadian system aligns behavior and physiology with the 24-hour environmental cycle through a distributed network of clocks including the master pacemaker in the suprachiasmatic nucleus (SCN) and an autonomous retinal clock critical for local retinal physiology and function. Although both clocks are entrained by light, they differ in their photoreceptor inputs and light sensitivity. The specific contributions and mechanisms by which distinct photoreceptor pathways drive their photoentrainment, however, remain incompletely understood. In this study, we conducted a comprehensive transcriptomic and integrative comparative analysis of retinal and SCN circadian responses to 530 nm monochromatic light using mouse models lacking specific photoreceptors or key components of signaling pathways. Under photopic conditions, we found that each tissue displays distinct light-responsive transcriptional signatures across genotypes, yet both shared a conserved cluster of rod-driven immediate early-genes. Strikingly, the light-evoked transcriptional response was not sufficient to shift the phase of the SCN clock, in contrast to its robust phase-shifting effect on the retinal clock. Furthermore, by genetically disrupting rod/cone electrical coupling and pharmacologically isolating rod pathways, we identified the OFF-cone bipolar cell circuit as both necessary and sufficient to mediate light-induced phase resetting of the retinal clock. Together, these findings delineate the specialized retinal circuitry that supports circadian entrainment and highlight a fundamental divergence between retinal and SCN mechanisms of photic timekeeping.
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BibTeX
@article{jandot2026divergent,
title = {{Divergent molecular and circuit mechanisms underlie light entrainment of retinal and suprachiasmatic nucleus circadian clocks}},
author = {Antonin Jandot and Hugo Calligaro and Arman Dianak-Shoori and Kévin Tartour and Cristina Sandu and Nasser Haddjeri and Christophe Ribelayga and Bharath Ananthasubramaniam and Kiran Padmanabhan and Marie-Paule Felder-Schmittbuhl and Ouria Dkhissi-Benyahya},
journal = {Cellular and Molecular Life Sciences},
year = {2026},
month = jun,
doi = {10.1007/s00018-026-06298-8},
url = {https://hal.science/hal-05674319v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Divergent molecular and circuit mechanisms underlie light entrainment of retinal and suprachiasmatic nucleus circadian clocks
AU - Antonin Jandot
AU - Hugo Calligaro
AU - Arman Dianak-Shoori
AU - Kévin Tartour
AU - Cristina Sandu
AU - Nasser Haddjeri
AU - Christophe Ribelayga
AU - Bharath Ananthasubramaniam
AU - Kiran Padmanabhan
AU - Marie-Paule Felder-Schmittbuhl
AU - Ouria Dkhissi-Benyahya
PY - 2026
DA - 2026/06/25
JO - Cellular and Molecular Life Sciences
DO - 10.1007/s00018-026-06298-8
UR - https://hal.science/hal-05674319v1
AB - The circadian system aligns behavior and physiology with the 24-hour environmental cycle through a distributed network of clocks including the master pacemaker in the suprachiasmatic nucleus (SCN) and an autonomous retinal clock critical for local retinal physiology and function. Although both clocks are entrained by light, they differ in their photoreceptor inputs and light sensitivity. The specific contributions and mechanisms by which distinct photoreceptor pathways drive their photoentrainment, however, remain incompletely understood. In this study, we conducted a comprehensive transcriptomic and integrative comparative analysis of retinal and SCN circadian responses to 530 nm monochromatic light using mouse models lacking specific photoreceptors or key components of signaling pathways. Under photopic conditions, we found that each tissue displays distinct light-responsive transcriptional signatures across genotypes, yet both shared a conserved cluster of rod-driven immediate early-genes. Strikingly, the light-evoked transcriptional response was not sufficient to shift the phase of the SCN clock, in contrast to its robust phase-shifting effect on the retinal clock. Furthermore, by genetically disrupting rod/cone electrical coupling and pharmacologically isolating rod pathways, we identified the OFF-cone bipolar cell circuit as both necessary and sufficient to mediate light-induced phase resetting of the retinal clock. Together, these findings delineate the specialized retinal circuitry that supports circadian entrainment and highlight a fundamental divergence between retinal and SCN mechanisms of photic timekeeping.
SN - 1420-682X
SN - 1420-9071
ER -