The VPAC(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(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.
Harmar
Anthony J
AJ
Department of Neuroscience, University of Edinburgh, 1 George Square, United Kingdom. tony.harmar@ed.ac.uk
Marston
Hugh M
HM
Shen
Sanbing
S
Spratt
Christopher
C
West
Katrine M
KM
Sheward
W John
WJ
Morrison
Christine F
CF
Dorin
Julia R
JR
Piggins
Hugh D
HD
Reubi
Jean Claude
JC
Kelly
John S
JS
Maywood
Elizabeth S
ES
Hastings
Michael H
MH
D056930:ARNTL Transcription Factors; D000818:Animals; D001127:Arginine Vasopressin / Q000235:genetics / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins; D001683:Biological Clocks / Q000235:genetics; D018797:Cell Cycle Proteins; D002940:Circadian Rhythm / Q000235:genetics*; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000235:genetics; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D009481:Neurophysins / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010451:Peptide PHI / Q000378:metabolism; D056950:Period Circadian Proteins; D010775:Photic Stimulation; D017956:Photoreceptor Cells, Invertebrate; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018005:Receptors, Vasoactive Intestinal Peptide / Q000172:deficiency* / Q000235:genetics; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D013493:Suprachiasmatic Nucleus / Q000378:metabolism* / Q000503:physiopathology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000528:radiation effects; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
D056930:ARNTL Transcription Factors; D001127:Arginine Vasopressin; D051792:Basic Helix-Loop-Helix Proteins; D018797:Cell Cycle Proteins; D056931:Cryptochromes; D029721:Drosophila Proteins; D005136:Eye Proteins; D005420:Flavoproteins; D009479:Neuropeptides; D009481:Neurophysins; D009687:Nuclear Proteins; D010451:Peptide PHI; D056950:Period Circadian Proteins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018005:Receptors, Vasoactive Intestinal Peptide; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014157:Transcription Factors; D014660:Vasoactive Intestinal Peptide; C495402:Adcyap1 protein, mouse; C538961:Bmal1 protein, mouse; C539023:Per1 protein, mouse; C513312:Per2 protein, mouse; C495510:Vipr2 protein, mouse; C119828:cry protein, Drosophila