A stress-sensing circuit signals to the central pacemaker to reprogram circadian rhythms

作者：Maria E. Yurgel, Claire Gao, John J. O’Malley, Qijun Tang, Noam Yanay, Alison R. Bashford, Jesse J. Zhan, Andrew Lutas, Michael J. Krashes, Haiqing Zhao, Mario A. Penzo, Samer Hattar · 发表于：Science Advances · 年份：2025 · DOI：10.1126/sciadv.adr7960 · 被引用次数：9 · 研究领域：Circadian rhythm and melatonin、Photoreceptor and optogenetics research、Spaceflight effects on biology

The circadian system provides a temporal framework for animals to anticipate environmental events, including threats. However, the effects of stressors on the circadian system remain poorly understood. Here, we demonstrate that, in mice, stressors shift the phase of the central pacemaker, housed in the suprachiasmatic nucleus (SCN), through glutamatergic inputs from the anterior paraventricular nucleus of the thalamus (aPVT). Unlike light, which can phase delay or advance the central pacemaker, stressors consistently induce delays, effects attenuated by inhibiting aPVT neurons. Stressors robustly activate AVP-expressing neurons within the SCN and are associated with inhibition of VIP-expressing neurons, whereas light strongly activates VIP-expressing neurons with minimal effects on AVP-expressing neurons. Pairing stressors with light reveals distinct time-dependent interactions, enhancing phase delays at early night but abolishing phase advances at late night. Our findings uncover distinct SCN microcircuits that differentially encode light and stressors, providing insights into how environmental cues modulate circadian timing.