Discrete photoentrainment of mammalian central clock is regulated by bi-stable dynamic network in the suprachiasmatic nucleus

Po-Ting Yeh, Kai-Chun Jhan, Ern-Pei Chua, Wun-Ci Chen, Shi-Wei Chu, Shun-Chi Wu and Shih-Kuo Chen ()
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Po-Ting Yeh: National Taiwan University
Kai-Chun Jhan: National Tsing Hua University
Ern-Pei Chua: National Taiwan University
Wun-Ci Chen: National Tsing Hua University
Shi-Wei Chu: National Taiwan University
Shun-Chi Wu: National Tsing Hua University
Shih-Kuo Chen: National Taiwan University

Nature Communications, 2025, vol. 16, issue 1, 1-15

Abstract: Abstract The biological clock synchronizes with the environmental light-dark cycle through circadian photoentrainment. While intracellular pathways regulating clock gene expression after light exposure in the suprachiasmatic nucleus are well studied in mammals, the neuronal circuits driving phase shifts remain unclear. Here, using a mouse model, we show that chemogenetic activation of early-night light-responsive neurons induces phase delays at any circadian time, potentially breaking the photoentrainment dead zone. In contrast, activating late-night light-responsive neurons mimics light-induced phase shifts. Using in vivo two-photon microscopy, we found that most neurons in the suprachiasmatic nucleus exhibit stochastic light responses, while a small subset is consistently activated in the early subjective night and another is inhibited in the late subjective night. Our findings suggest a dynamic bi-stable network model for circadian photoentrainment, where phase shifts arise from a functional circuit integrating signals to groups of outcome neurons, rather than a labeled-line principle seen in sensory systems.

Date: 2025
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DOI: 10.1038/s41467-025-58661-1

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