ArticleProceedings of the National Academy of Sciences of the United States of America2011
A diversity of paracrine signals sustains molecular circadian cycling in suprachiasmatic nucleus circuits.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 184 papers.
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Who cites it
184 citing papers in PubMed.
- Attractive and repulsive couplings between circadian pacemaker neurons promote entrainment to light-dark cycles with after-effect.Npj biological timing and sleep · 2026Article
- Defining Clock Neurons Within Distributed Circadian Circuits Through Multiscale Technologies.Journal of biological rhythms · 2026Review
- The suprachiasmatic nucleus: a central pacemaker for temporal coordination of energy metabolic homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- GABAergic projections from the suprachiasmatic nucleus to the preoptic area regulate the timing of torpor in mice.Nature communications · 2026Article
- Toward dissection of diverse neural components in the suprachiasmatic nucleus (SCN) pacemaker network.Neurobiology of sleep and circadian rhythms · 2026Article
- Reconsidering mammalian circadian organization.Neurobiology of sleep and circadian rhythms · 2026Article
- Article
- Heterogeneity between VIP and GRP neurons underlies AVP receptor signaling in the mouse suprachiasmatic nucleus.Communications biology · 2026Article
- The inferred functional connectome underlying circadian synchronization in the mouse suprachiasmatic nucleus.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Somatostatin regulates the clock sensitivity to evening light.Scientific reports · 2025Article
- Synaptic targets of circadian clock neurons influence core clock parameters.Science advances · 2025Article
- Biological Fluid Flows: Signaling Mediums for Circadian Timing.Journal of biological rhythms · 2025Review
- Mutual coupling of neurons in the circadian master clock: What we can learn from fruit flies.Neurobiology of sleep and circadian rhythms · 2025Article
- The cell-intrinsic circadian clock is dispensable for lateral posterior clock neuron regulation ofNeurobiology of sleep and circadian rhythms · 2025Article
- Suprachiasmatic nucleus-wide estimation of oscillatory temporal dynamics.PLoS computational biology · 2025Article
- Synaptic Targets of Circadian Clock Neurons Influence Core Clock Parameters.bioRxiv : the preprint server for biology · 2025Article
- Development of compounds for targeted degradation of mammalian cryptochrome proteins.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Neuropeptidergic Input from the Lateral Hypothalamus to the Suprachiasmatic Nucleus Alters the Circadian Period in Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- Harnessing the circadian nature of the choroid plexus and cerebrospinal fluid.Npj biological timing and sleep · 2025Review
- The Functional Connectome Mediating Circadian Synchrony in the Suprachiasmatic Nucleus.bioRxiv : the preprint server for biology · 2024Article
124 more citing papers are in PubMed but not listed here.
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Abstract
The suprachiasmatic nucleus (SCN) is the principal circadian pacemaker of mammals, coordinating daily rhythms of behavior and metabolism. Circadian timekeeping in SCN neurons revolves around transcriptional/posttranslational feedback loops, in which Period (Per) and Cryptochrome (Cry) genes are negatively regulated by their protein products. Recent studies have revealed, however, that these "core loops" also rely upon cytosolic and circuit-level properties for sustained oscillation. To characterize interneuronal signals responsible for robust pacemaking in SCN cells and circuits, we have developed a unique coculture technique using wild-type (WT) "graft" SCN to drive pacemaking (reported by PER2::LUCIFERASE bioluminescence) in "host" SCN deficient either in elements of neuropeptidergic signaling or in elements of the core feedback loop. We demonstrate that paracrine signaling is sufficient to restore cellular synchrony and amplitude of pacemaking in SCN circuits lacking vasoactive intestinal peptide (VIP). By using grafts with mutant circadian periods we show that pacemaking in the host SCN is specified by the genotype of the graft, confirming graft-derived factors as determinants of the host rhythm. By combining pharmacological with genetic manipulations, we show that a hierarchy of neuropeptidergic signals underpins this paracrine regulation, with a preeminent role for VIP augmented by contributions from arginine vasopressin (AVP) and gastrin-releasing peptide (GRP). Finally, we show that interneuronal signaling is sufficiently powerful to maintain circadian pacemaking in arrhythmic Cry-null SCN, deficient in essential elements of the transcriptional negative feedback loops. Thus, a hierarchy of paracrine neuropeptidergic signals determines cell- and circuit-level circadian pacemaking in the SCN.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.