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Nat Commun. 2019 Feb 1;10(1):542. doi: 10.1038/s41467-019-08427-3.

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

Author information

1
MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge, CB2 0QH, UK.
2
Department of Neurosurgery, Stanford University, 318 Campus Drive, Stanford, CA, 94305, USA.
3
MRC Laboratory of Molecular Biology, Francis Crick Ave, Cambridge, CB2 0QH, UK. mha@mrc-lmb.cam.ac.uk.

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.

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