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- PMID: 23623697
- UKPMCID: 23623697
- DOI: 10.1016/j.neuron.2013.03.011
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A Gq-Ca2+ axis controls circuit-level encoding of circadian time in the suprachiasmatic nucleus.
Brancaccio, Marco; Maywood, Elizabeth S; Chesham, Johanna E; Loudon, Andrew S I; Hastings, Michael H
Neuron. 2013;78(4):714-28.
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Full-text held externally
- PMID: 23623697
- UKPMCID: 23623697
- DOI: 10.1016/j.neuron.2013.03.011
Abstract
The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) is well established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to the intercellular control of SCN pacemaking are poorly understood. We therefore combined viral transduction of SCN slices with fluorescence/bioluminescence imaging to visualize GCaMP3-reported circadian oscillations of intracellular calcium [Ca2+]i alongside activation of Ca2+ /cAMP-responsive elements. We phase-mapped them to the TTFL, in time and SCN space, and demonstrated their dependence upon G-coupled vasoactive intestinal peptide (VIP) signaling. Pharmacogenetic manipulation revealed the individual contributions of Gq, Gs, and Gi to cytosolic and TTFL circadian rhythms. Importantly, activation of Gq-dependent (but not Gs or Gi) pathways in a minority of neurons reprogrammed [Ca2+]i and TTFL rhythms across the entire SCN. This reprogramming was mediated by intrinsic VIPergic signaling, thus revealing a Gq/[Ca2+]i-VIP leitmotif and unanticipated plasticity within network encoding of SCN circadian time.