Living organisms adapt to the natural 24-hour daily cycle through the circadian system, which acts as an internal timer. This system helps organisms anticipate and adapt to environmental threats. The suprachiasmatic nucleus (SCN), located in the hypothalamus of the brain, integrates both photic and non-photic stimuli and ensures that the circadian system works regularly. Through this role, the SCN, recognized as the brain’s central pacemaker, enables organisms to show adaptive behaviors in response to environmental threats. However, in humans, aversive stimuli such as stress can disrupt circadian rhythms. Such circadian disruptions are often associated with altered sleep patterns and hormonal imbalances in humans. Recent research has investigated how the SCN detects stressors and modulates circadian rhythms.
In a study conducted by Maria E. Yurgel and colleagues, the effects of stress factors on the SCN and circadian rhythm were examined. In the study, C57BL/6J mice were used as model organisms. The researchers examined how NMS, AVP, and VIP neurons in the SCN responded to environmental stressors (such as light, foot shock, and forced swimming). Stressors were applied to the mice at different circadian phases, and neuronal responses were analyzed using techniques such as fiber photometry (to monitor real-time calcium activity in neuronal populations), chemogenetic modulation (to selectively activate or inhibit neurons using engineered receptors), and two-photon calcium imaging (for high-resolution, cellular-level neuronal visualization).
The study also highlighted the anterior paraventricular thalamus (aPVT), a key relay center connecting stress pathways to the circadian system. The aPVT-SCN circuit was described as having strong anatomical and functional connections. Furthermore, glutamatergic neurons in the aPVT were observed to become active in response to negative stimuli and send signals to the SCN. Each signal was found to activate distinct SCN microcircuits, generating different responses in the subtypes of SCN neurons: arginine vasopressin (AVP), vasoactive intestinal peptide (VIP), and Neuromedin S (NMS) neurons of the SCN.
Particularly, it was observed that stress factors primarily activated AVP neurons located in the shell region of the SCN, while photic stimuli strongly activated VIP neurons in the core region of the SCN. NMS neurons, on the other hand, were observed to modulate both excitatory and inhibitory responses, helping to control circadian timing. Taken together, the results demonstrate that the SCN modulates its responses in a time-of-day–dependent manner, influenced by the animal’s physiological state and exposure to stress.
In conclusion, the study demonstrates that stressors can disrupt the circadian rhythm. Moreover, these stressors were shown to relay signals to the SCN via the aPVT. It also reveals how distinct stimuli trigger different responses within the SCN. These findings form the basis for understanding the neuronal mechanisms of psychiatric disorders caused by circadian rhythm disorders and may pave the way for new therapeutic strategies for these psychiatric disorders.
Author: Altınay Gün
Editor: Pelinsu Albey
Reference: Maria E. Yurgel et al., A stress-sensing circuit signals to the central pacemaker to reprogram circadian rhythms. Science (2025). https://www.science.org/doi/10.1126/sciadv.adr7960
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