title: A Gq-Ca2+ axis controls circuit-level encoding of circadian time in the suprachiasmatic nucleus.
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.
authors.affiliation: Division of Neurobiology, Medical Research Council Laboratory of Molecular Biology, Cambridge CB2 0QH, UK.
authors.forename: Marco
authors.initials: M
authors.lastname: Brancaccio
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Maywood
authors.forename: Johanna E
authors.initials: JE
authors.lastname: Chesham
authors.forename: Andrew S I
authors.initials: AS
authors.lastname: Loudon
authors.forename: Michael H
authors.initials: MH
authors.lastname: Hastings
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D057906:Circadian Clocks / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D015290:Second Messenger Systems / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000502:physiology*
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D044385:GTP-Binding Protein alpha Subunits; D014660:Vasoactive Intestinal Peptide; D019206:GTP-Binding Protein alpha Subunits, Gi-Go; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019205:GTP-Binding Protein alpha Subunits, Gs