Vasoactive intestinal peptide controls the suprachiasmatic circadian clock network via ERK1/2 and DUSP4 signalling

Ryan Hamnett, Priya Crosby, Johanna E. Chesham and Michael H. Hastings ()
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Ryan Hamnett: MRC Laboratory of Molecular Biology
Priya Crosby: MRC Laboratory of Molecular Biology
Johanna E. Chesham: MRC Laboratory of Molecular Biology
Michael H. Hastings: MRC Laboratory of Molecular Biology

Nature Communications, 2019, vol. 10, issue 1, 1-17

Abstract: Abstract The suprachiasmatic nucleus (SCN) co-ordinates circadian behaviour and physiology in mammals. Its cell-autonomous circadian oscillations pivot around a well characterised transcriptional/translational feedback loop (TTFL), whilst the SCN circuit as a whole is synchronised to solar time by its retinorecipient cells that express and release vasoactive intestinal peptide (VIP). The cell-autonomous and circuit-level mechanisms whereby VIP synchronises the SCN are poorly understood. We show that SCN slices in organotypic culture demonstrate rapid and sustained circuit-level circadian responses to VIP that are mediated at a cell-autonomous level. This is accompanied by changes across a broad transcriptional network and by significant VIP-directed plasticity in the internal phasing of the cell-autonomous TTFL. Signalling via ERK1/2 and tuning by its negative regulator DUSP4 are critical elements of the VIP-directed circadian re-programming. In summary, we provide detailed mechanistic insight into VIP signal transduction in the SCN at the level of genes, cells and neural circuit.

Date: 2019
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DOI: 10.1038/s41467-019-08427-3

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