The VIP-VPAC2 neuropeptidergic axis is a cellular pacemaking hub of the suprachiasmatic nucleus circadian circuit

Andrew P. Patton, Mathew D. Edwards, Nicola J. Smyllie, Ryan Hamnett, Johanna E. Chesham, Marco Brancaccio, Elizabeth S. Maywood and Michael H. Hastings ()
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Andrew P. Patton: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Mathew D. Edwards: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Nicola J. Smyllie: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Ryan Hamnett: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Johanna E. Chesham: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Marco Brancaccio: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Elizabeth S. Maywood: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus
Michael H. Hastings: MRC Laboratory of Molecular Biology, Francis Crick Ave., Cambridge Biomedical Campus

Nature Communications, 2020, vol. 11, issue 1, 1-17

Abstract: Abstract The hypothalamic suprachiasmatic nuclei (SCN) are the principal mammalian circadian timekeeper, co-ordinating organism-wide daily and seasonal rhythms. To achieve this, cell-autonomous circadian timing by the ~20,000 SCN cells is welded into a tight circuit-wide ensemble oscillation. This creates essential, network-level emergent properties of precise, high-amplitude oscillation with tightly defined ensemble period and phase. Although synchronised, regional cell groups exhibit differentially phased activity, creating stereotypical spatiotemporal circadian waves of cellular activation across the circuit. The cellular circuit pacemaking components that generate these critical emergent properties are unknown. Using intersectional genetics and real-time imaging, we show that SCN cells expressing vasoactive intestinal polypeptide (VIP) or its cognate receptor, VPAC2, are neurochemically and electrophysiologically distinct, but together they control de novo rhythmicity, setting ensemble period and phase with circuit-level spatiotemporal complexity. The VIP/VPAC2 cellular axis is therefore a neurochemically and topologically specific pacemaker hub that determines the emergent properties of the SCN timekeeper.

Date: 2020
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DOI: 10.1038/s41467-020-17110-x

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