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

Marco Brancaccio; ElizabethS Maywood; JohannaE Chesham; AndrewS I. Loudon; MichaelH Hastings

doi:10.1016/j.neuron.2013.03.011

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

Marco Brancaccio, ElizabethS Maywood, JohannaE Chesham, AndrewS I. Loudon, MichaelH Hastings

Research output: Contribution to journal › Article › peer-review

Abstract

The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) iswell established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to theintercellular 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

Original language	English
Pages (from-to)	714-728
Number of pages	14
Journal	Neuron
Volume	78
Issue number	4
DOIs	https://doi.org/10.1016/j.neuron.2013.03.011
Publication status	Published - 22 May 2013

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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) iswell established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to theintercellular 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",

author = "Marco Brancaccio and ElizabethS Maywood and JohannaE Chesham and Loudon, {AndrewS I.} and MichaelH Hastings",

note = "BB/E023223/1, Biotechnology and Biological Sciences Research Council, United Kingdom, Medical Research Council, United Kingdom",

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T1 - A Gq-Ca2+ Axis controls circuit-level encoding of circadian time in the suprachiasmatic nucleus

AU - Brancaccio, Marco

AU - Maywood, ElizabethS

AU - Chesham, JohannaE

AU - Loudon, AndrewS I.

AU - Hastings, MichaelH

N1 - BB/E023223/1, Biotechnology and Biological Sciences Research Council, United Kingdom, Medical Research Council, United Kingdom

PY - 2013/5/22

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N2 - The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) iswell established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to theintercellular 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

AB - The role of intracellular transcriptional/post-translational feedback loops (TTFL) within the circadian pacemaker of the suprachiasmatic nucleus (SCN) iswell established. In contrast, contributions from G-coupled pathways and cytosolic rhythms to theintercellular 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

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DO - 10.1016/j.neuron.2013.03.011

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VL - 78

SP - 714

EP - 728

JO - Neuron

JF - Neuron

IS - 4

ER -

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

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