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.

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
  • Arntl 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