The VPAC sub(2) Receptor Is Essential for Circadian Function in the Mouse Suprachiasmatic Nuclei

The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are implicated in the photic entrainment of circadian rhythms in the suprachiasmatic nuclei (SCN). We now report that mice carrying a null mutation of the VPAC sub(2) receptor for VIP...

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Published in:Cell 2002-05, Vol.109 (4), p.497-508
Main Authors: Harmar, AJ, Marston, H M, Shen, Sanbing, Spratt, C, West, K M, Sheward, W J, Morrison, C F, Dorin, J R, Piggins, H D, Reubi, J-C, Kelly, J S, Maywood, E S, Hastings, M H
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Language:English
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Summary:The neuropeptides pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal peptide (VIP) are implicated in the photic entrainment of circadian rhythms in the suprachiasmatic nuclei (SCN). We now report that mice carrying a null mutation of the VPAC sub(2) receptor for VIP and PACAP (Vipr2 super(-/-)) are incapable of sustaining normal circadian rhythms of rest/activity behavior. These mice also fail to exhibit circadian expression of the core clock genes mPer1, mPer2, and mCry1 and clock-controlled gene arginine vasopressin (AVP) in the SCN. Moreover, the mutants fail to show acute induction of mPer1 and mPer2 by nocturnal illumination. This study highlights the role of intercellular neuropeptidergic signaling in maintenance of circadian function within the SCN.
ISSN:0092-8674