Beyond the light-driven pacemaker: the suprachiasmatic nucleus as a dynamic coordinator of environmental cues
5 affiliations
- 1Jiangsu Province Engineering Research Center of Development and Translation of Key Technologies for Chronic Disease Prevention and Control, Suzhou Vocational Health College
- 2Orthopaedic Institute, Wuxi Ninth People's Hospital Affiliated to Soochow University
- 3Peking University-Nanjing Institute of Translational Medicine
- 4College of Pharmacy, Suzhou Vocational Health College
- 5Core Facility, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People's Hospital, Quzhou
Abstract
The suprachiasmatic nucleus (SCN) is the central mammalian circadian pacemaker, but its function extends beyond passive entrainment to light. Here, we synthesize evidence that the SCN is a heterogeneous and plastic network that integrates photic, metabolic, astrocytic, and thermal information across daily entrainment, seasonal adaptation, jet lag, and chronic circadian misalignment. VIP and GRP neurons provide privileged access for retinal input and network synchronization, AVP neurons support intrinsic rhythmicity and output, and the broad Nms -expressing ensemble and CCK-defined subtypes contribute to arousal and adaptive network plasticity. We propose an integrative circuit model in which retinal signals preferentially engage core VIP/GRP neurons, whereas feeding and metabolic information influences VIP and AVP populations through circulating factors, the dorsomedial hypothalamus, the intergeniculate leaflet, and metabolically responsive astrocytes. Rhythmic astrocytic GABA and glutamate release, together with VIP-AVP coupling and overlapping VIP ⁺ /NMS ⁺ and AVP ⁺ /NMS ⁺ subpopulations, may coordinate phase resetting and sleep-wake rhythms. The timing mechanism underlying food anticipatory activity (FAA) is attributed primarily to distributed extra-SCN food-entrainable circuits, whereas the SCN may gate or modulate its behavioral expression rather than generate it autonomously. Light remains the dominant zeitgeber. Under standard light-dark conditions, time-restricted feeding more commonly modulates SCN neuronal activity, calcium dynamics, neuropeptide output, and behavior than resets the core TTFL; molecular resetting has been reported only under specific genetic, temporal, dietary, lighting, or network conditions. When light and feeding cues conflict, rapid ventral resetting and slower dorsal reentrainment generate transient intranuclear and systemic desynchrony rather than simple dominance by either cue. Biological sex and aging further shape this integrative capacity, while temperature compensation delineates the boundary between resistance to routine thermal fluctuations and conditional responses to stronger thermal challenges. This framework helps explain circadian disruption in jet lag, shift work, social jetlag, and metabolic disease, and supports circadian medicine strategies that align timed light, feeding, exercise, sleep, and pharmacotherapy across central and peripheral clocks.
Related
- Monosynaptic GABAergic projections from a subset of suprachiasmatic nucleus neuromedin S neurons suppress preoptic area kisspeptin neuron firing in female mice
- Heart Failure Readmissions and Dedicated Inpatient Coordinator–Led Transitional Care
- An Explainable Multi-Modal Deep Learning Framework for Investigating the Influences of Dynamic Environmental Exposure on Momentary Stress.
- The cognition of dynamic evaluation of operating room environmental quality among medical staff: a qualitative study
- Dynamic analysis and chaos control of an environmental population model incorporating the wind flow in a stochastic and deterministic perspective
BibTeX
@article{zhang2026beyond,
title = {{Beyond the light-driven pacemaker: the suprachiasmatic nucleus as a dynamic coordinator of environmental cues}},
author = {Tao Zhang and Kai Huang and Jing Yu and Shaojun Wu and Qiaocheng Zhai},
journal = {Frontiers in Neuroscience},
year = {2026},
month = oct,
doi = {10.3389/fnins.2026.1937340},
url = {https://www.frontiersin.org/articles/10.3389/fnins.2026.1937340/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Beyond the light-driven pacemaker: the suprachiasmatic nucleus as a dynamic coordinator of environmental cues
AU - Tao Zhang
AU - Kai Huang
AU - Jing Yu
AU - Shaojun Wu
AU - Qiaocheng Zhai
PY - 2026
DA - 2026/10/09
JO - Frontiers in Neuroscience
DO - 10.3389/fnins.2026.1937340
UR - https://www.frontiersin.org/articles/10.3389/fnins.2026.1937340/full
AB - The suprachiasmatic nucleus (SCN) is the central mammalian circadian pacemaker, but its function extends beyond passive entrainment to light. Here, we synthesize evidence that the SCN is a heterogeneous and plastic network that integrates photic, metabolic, astrocytic, and thermal information across daily entrainment, seasonal adaptation, jet lag, and chronic circadian misalignment. VIP and GRP neurons provide privileged access for retinal input and network synchronization, AVP neurons support intrinsic rhythmicity and output, and the broad Nms -expressing ensemble and CCK-defined subtypes contribute to arousal and adaptive network plasticity. We propose an integrative circuit model in which retinal signals preferentially engage core VIP/GRP neurons, whereas feeding and metabolic information influences VIP and AVP populations through circulating factors, the dorsomedial hypothalamus, the intergeniculate leaflet, and metabolically responsive astrocytes. Rhythmic astrocytic GABA and glutamate release, together with VIP-AVP coupling and overlapping VIP ⁺ /NMS ⁺ and AVP ⁺ /NMS ⁺ subpopulations, may coordinate phase resetting and sleep-wake rhythms. The timing mechanism underlying food anticipatory activity (FAA) is attributed primarily to distributed extra-SCN food-entrainable circuits, whereas the SCN may gate or modulate its behavioral expression rather than generate it autonomously. Light remains the dominant zeitgeber. Under standard light-dark conditions, time-restricted feeding more commonly modulates SCN neuronal activity, calcium dynamics, neuropeptide output, and behavior than resets the core TTFL; molecular resetting has been reported only under specific genetic, temporal, dietary, lighting, or network conditions. When light and feeding cues conflict, rapid ventral resetting and slower dorsal reentrainment generate transient intranuclear and systemic desynchrony rather than simple dominance by either cue. Biological sex and aging further shape this integrative capacity, while temperature compensation delineates the boundary between resistance to routine thermal fluctuations and conditional responses to stronger thermal challenges. This framework helps explain circadian disruption in jet lag, shift work, social jetlag, and metabolic disease, and supports circadian medicine strategies that align timed light, feeding, exercise, sleep, and pharmacotherapy across central and peripheral clocks.
SN - 1662-453X
SN - 1662-4548
ER -