ArticlePLoS computational biology2014
Timing of neuropeptide coupling determines synchrony and entrainment in the mammalian circadian clock.
Article in PLoS computational biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Theoretical chronobiology of circadian timing-gold mine or minefield?Npj biological timing and sleep · 2026Review
- Time after time - circadian clocks through the lens of oscillator theory.FEBS letters · 2026Review
- An Automated Organotypic SCN Culture System Revealing Novel Insights into VIP Regulation of Circadian Rhythm.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- Synaptic targets of circadian clock neurons influence core clock parameters.Science advances · 2025Article
- Synaptic Targets of Circadian Clock Neurons Influence Core Clock Parameters.bioRxiv : the preprint server for biology · 2025Article
- Astrocytes actively support long-range molecular clock synchronization of segregated neuronal populations.Scientific reports · 2023Article
- UBR4/POE facilitates secretory trafficking to maintain circadian clock synchrony.Nature communications · 2022Article
- A spatio-temporal model to reveal oscillator phenotypes in molecular clocks: Parameter estimation elucidates circadian gene transcription dynamics in single-cells.PLoS computational biology · 2021Article
- Complementary phase responses via functional differentiation of dual negative feedback loops.PLoS computational biology · 2021Article
- Cancer stem cell generation during epithelial-mesenchymal transition is temporally gated by intrinsic circadian clocks.Clinical & experimental metastasis · 2020Article
- Reduced VIP Expression Affects Circadian Clock Function in VIP-IRES-CRE Mice (JAX 010908).Journal of biological rhythms · 2020Article
- Recurring circadian disruption alters circadian clock sensitivity to resetting.The European journal of neuroscience · 2020Article
- A Symphony of Signals: Intercellular and Intracellular Signaling Mechanisms Underlying Circadian Timekeeping in Mice and Flies.International journal of molecular sciences · 2019Review
- Filtering and inference for stochastic oscillators with distributed delays.Bioinformatics (Oxford, England) · 2019Article
- Coherency of circadian rhythms in the SCN is governed by the interplay of two coupling factors.PLoS computational biology · 2018Article
- Stability of Wake-Sleep Cycles Requires Robust Degradation of the PERIOD Protein.Current biology : CB · 2017Article
- Fluorescence circadian imaging reveals a PDF-dependent transcriptional regulation of the Drosophila molecular clock.Scientific reports · 2017Article
- An LHX1-Regulated Transcriptional Network Controls Sleep/Wake Coupling and Thermal Resistance of the Central Circadian Clockworks.Current biology : CB · 2017Article
- Differential roles of AVP and VIP signaling in the postnatal changes of neural networks for coherent circadian rhythms in the SCN.Science advances · 2016Article
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Robust synchronization is a critical feature of several systems including the mammalian circadian clock. The master circadian clock in mammals consists of about 20000 'sloppy' neuronal oscillators within the hypothalamus that keep robust time by synchronization driven by inter-neuronal coupling. The complete understanding of this synchronization in the mammalian circadian clock and the mechanisms underlying it remain an open question. Experiments and computational studies have shown that coupling individual oscillators can achieve robust synchrony, despite heterogeneity and different network topologies. But, much less is known regarding the mechanisms and circuits involved in achieving this coupling, due to both system complexity and experimental limitations. Here, we computationally study the coupling mediated by the primary coupling neuropeptide, vasoactive intestinal peptide (VIP) and its canonical receptor, VPAC2R, using the transcriptional elements and generic mode of VIP-VPAC2R signaling. We find that synchrony is only possible if VIP (an inducer of Per expression) is released in-phase with activators of Per expression. Moreover, anti-phasic VIP release suppresses coherent rhythms by moving the network into a desynchronous state. Importantly, experimentally observed rhythms in VPAC2R have little effect on network synchronization, but can improve the amplitude of the SCN network rhythms while narrowing the network entrainment range. We further show that these findings are valid across several computational network models. Thus, we identified a general design principle to achieve robust synchronization: An activating coupling agent, such as VIP, must act in-phase with the activity of core-clock promoters. More generally, the phase of coupling is as critical as the strength of coupling from the viewpoint of synchrony and entrainment.
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Registered trials
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.