Beyond the light-driven pacemaker: the suprachiasmatic nucleus as a dynamic coordinator of environmental cues

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.