The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei

Anthony J Harmar; Hugh M Marston; Sanbing Shen; Christopher Spratt; Katrine M West; W John Sheward; Christine F Morrison; Julia R Dorin; Hugh D Piggins; Jean Claude Reubi; John S Kelly; Elizabeth S Maywood; Michael H Hastings

doi:10.1016/s0092-8674(02)00736-5

The VPAC(2) receptor is essential for circadian function in the mouse suprachiasmatic nuclei

Cell. 2002 May 17;109(4):497-508. doi: 10.1016/s0092-8674(02)00736-5.

Authors

Anthony J Harmar¹, Hugh M Marston, Sanbing Shen, Christopher Spratt, Katrine M West, W John Sheward, Christine F Morrison, Julia R Dorin, Hugh D Piggins, Jean Claude Reubi, John S Kelly, Elizabeth S Maywood, Michael H Hastings

Affiliation

¹ Department of Neuroscience, University of Edinburgh, 1 George Square, United Kingdom. tony.harmar@ed.ac.uk

PMID: 12086606
DOI: 10.1016/s0092-8674(02)00736-5

Abstract

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(2) receptor for VIP and PACAP (Vipr2(-/-)) 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 the 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ARNTL Transcription Factors
Animals
Arginine Vasopressin / genetics
Arginine Vasopressin / metabolism
Basic Helix-Loop-Helix Transcription Factors
Biological Clocks / genetics
Cell Cycle Proteins
Circadian Rhythm / genetics*
Cryptochromes
Drosophila Proteins*
Eye Proteins*
Flavoproteins / genetics
Flavoproteins / metabolism
Gene Expression Regulation / genetics*
Male
Mice
Mice, Knockout
Motor Activity / genetics
Mutation / genetics
Neurons / metabolism*
Neuropeptides / metabolism*
Neurophysins / metabolism
Nuclear Proteins / genetics
Nuclear Proteins / metabolism
Peptide PHI / metabolism
Period Circadian Proteins
Photic Stimulation
Photoreceptor Cells, Invertebrate*
Pituitary Adenylate Cyclase-Activating Polypeptide
RNA, Messenger / metabolism
Receptors, G-Protein-Coupled
Receptors, Vasoactive Intestinal Peptide / deficiency*
Receptors, Vasoactive Intestinal Peptide / genetics
Receptors, Vasoactive Intestinal Peptide, Type II
Suprachiasmatic Nucleus / metabolism*
Suprachiasmatic Nucleus / physiopathology
Transcription Factors / genetics
Transcription Factors / metabolism
Up-Regulation / radiation effects
Vasoactive Intestinal Peptide / metabolism*

Substances

ARNTL Transcription Factors
Adcyap1 protein, mouse
Bmal1 protein, mouse
Basic Helix-Loop-Helix Transcription Factors
Cell Cycle Proteins
Cryptochromes
Drosophila Proteins
Eye Proteins
Flavoproteins
Neuropeptides
Neurophysins
Nuclear Proteins
Peptide PHI
Per1 protein, mouse
Per2 protein, mouse
Period Circadian Proteins
Pituitary Adenylate Cyclase-Activating Polypeptide
RNA, Messenger
Receptors, G-Protein-Coupled
Receptors, Vasoactive Intestinal Peptide
Receptors, Vasoactive Intestinal Peptide, Type II
Transcription Factors
Vipr2 protein, mouse
cry protein, Drosophila
Arginine Vasopressin
Vasoactive Intestinal Peptide