A Gq-Ca2+ axis controls circuit-level encoding of circadian time in the suprachiasmatic nucleus

Neuron. 2013 May 22;78(4):714-28. doi: 10.1016/j.neuron.2013.03.011. Epub 2013 Apr 25.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Signaling / physiology*
  • Circadian Clocks / physiology*
  • Cyclic AMP Response Element-Binding Protein / metabolism*
  • Feedback, Physiological / physiology
  • GTP-Binding Protein alpha Subunits / metabolism*
  • GTP-Binding Protein alpha Subunits, Gi-Go / metabolism
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Mutant Strains
  • Mice, Transgenic
  • Second Messenger Systems / physiology
  • Signal Transduction / physiology
  • Suprachiasmatic Nucleus / metabolism*
  • Vasoactive Intestinal Peptide / physiology*

Substances

  • Cyclic AMP Response Element-Binding Protein
  • GTP-Binding Protein alpha Subunits
  • Vasoactive Intestinal Peptide
  • GTP-Binding Protein alpha Subunits, Gi-Go
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Protein alpha Subunits, Gs