Synchronization and Maintenance of Timekeeping in Suprachiasmatic Circadian Clock Cells by Neuropeptidergic Signaling
Open accessAbstract
Circadian timekeeping in mammals is driven by transcriptional/posttranslational feedback loops that are active within both peripheral tissues and the circadian pacemaker of the suprachiasmatic nuclei (SCN). Spontaneous synchronization of these molecular loops between SCN neurons is a primary requirement of its pacemaker role and distinguishes it from peripheral tissues, which require extrinsic, SCN-dependent cues to impose cellular synchrony. Vasoactive intestinal polypeptide (VIP) is an intrinsic SCN factor implicated in acute activation and electrical synchronization of SCN neurons and coordination of behavioral rhythms. Using real-time imaging of cellular circadian gene expression across entire SCN slice cultures, we show for the first time that the Vipr2 gene encoding the VPAC2 receptor for VIP is necessary both to maintain molecular timekeeping within individual SCN neurons and to synchronize molecular timekeeping between SCN neurons embedded within intact, organotypical circuits. Moreover, we demonstrate that both depolarization and a second SCN neuropeptide, gastrin-releasing peptide (GRP), can acutely enhance and synchronize molecular timekeeping in Vipr2-/- SCN neurons. Nevertheless, transiently activated and synchronized Vipr2-/- cells cannot sustain synchrony in the absence of VIP-ergic signaling. Hence, neuropeptidergic interneuronal signaling confers a canonical property upon the SCN: spontaneous synchronization of the intracellular molecular clockworks of individual neurons.
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In aging, communication between SCN neurons is likely compromised because of low expression of vasoactive intestinal polypeptide, an essential factor in electrical synchronization of SCN neurons.
“This is an interesting observation with respect to aging, where communication between SCN neurons is likely to be compromised because of low expression of vasoactive intestinal polypeptide, an essential factor in electrical synchronization of SCN neurons [56].”
From Sleep, vigilance, and thermosensitivity (2012) · cites this paper as [56]
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- Authors
- Maywood, E. S., Reddy, A. B., Wong, G. K. Y., O'Neill, J. S., O'Brien, J. A., McMahon, D. G., Harmar, A. J., Okamura, H., & Hastings, M. H.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Vanderbilt University (US)
- University of Edinburgh (GB)
- Kobe University (JP)
- Corresponding author
- Maywood, Elizabeth S.
- ORCID
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 16
- Issue
- 6
- Pages
- 599-605
- ISSN
- 0960-9822 (ISSN-L)
- OpenAlex
- W2032793852
- Cited by
- 438
- References
- 36
- Citations by year
- 2026: 9 · 2025: 5 · 2024: 13 · 2023: 15 · 2022: 11 · 2021: 18 · 2020: 21 · 2019: 13 · 2018: 23 · 2017: 12 · 2016: 19 · 2015: 20 · 2014: 26 · 2013: 28 · 2012: 27
- FWCI
- 15.27
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2731 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Biotechnology and Biological Sciences Research Council (BB/006941/1)
- Wellcome Trust
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- suprachiasmatic nucleus, circadian clock, neuronal synchronization, vasoactive intestinal peptide, VIPR2, VPAC2 receptor, gastrin-releasing peptide, circadian gene expression, slice culture, depolarization
- MeSH terms
- Animals, Circadian Rhythm, Neurons, Neuropeptides, Recombinant Fusion Proteins, Suprachiasmatic Nucleus, Signal Transduction, Genes, Reporter, Gastrin-Releasing Peptide, Feedback, Physiological, Green Fluorescent Proteins, Receptors, Vasoactive Intestinal Peptide, Type II, Mice
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