| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
MODEL ORGANISMS AND COMPARATIVE FUNCTIONAL GENOMICS
Mental Retardation Research Center, Department of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, California 90024-1759
Submitted 15 April 2003 ; accepted in final form 4 July 2003
The related neuropeptides vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are expressed at high levels in the neurons of the suprachiasmatic nucleus (SCN), but their function in the regulation of circadian rhythms is unknown. To study the role of these peptides on the circadian system in vivo, a new mouse model was developed in which both VIP and PHI genes were disrupted by homologous recombination. In a light-dark cycle, these mice exhibited diurnal rhythms in activity which were largely indistinguishable from wild-type controls. In constant darkness, the VIP/PHI-deficient mice exhibited pronounced abnormalities in their circadian system. The activity patterns started 
8 h earlier than predicted by the previous light cycle. In addition, lack of VIP/PHI led to a shortened free-running period and a loss of the coherence and precision of the circadian locomotor activity rhythm. In about one-quarter of VIP/PHI mice examined, the wheel-running rhythm became arrhythmic after several weeks in constant darkness. Another striking example of these deficits is seen in the split-activity patterns expressed by the mutant mice when they were exposed to a skeleton photoperiod. In addition, the VIP/PHI-deficient mice exhibited deficits in the response of their circadian system to light. Electrophysiological analysis indicates that VIP enhances inhibitory synaptic transmission within the SCN of wild-type and VIP/PHI-deficient mice. Together, the observations suggest that VIP/PHI peptides are critically involved in both the generation of circadian oscillations as well as the normal synchronization of these rhythms to light.
peptide histidine isoleucine; vasoactive intestinal peptide; suprachiasmatic nucleus; GABA; inhibitory postsynaptic currents
This article has been cited by other articles:
|
|
 |
|
  A.T.L. Hughes and H.D. Piggins Behavioral Responses of Vipr2-/- Mice to Light J Biol Rhythms, June 1, 2008; 23(3): 211 - 219. [Abstract] [PDF]
|
|
|
|
 |
|
 D. A. Bechtold, T. M. Brown, S. M. Luckman, and H. D. Piggins Metabolic rhythm abnormalities in mice lacking VIP-VPAC2 signaling Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R344 - R351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Gamble, G. C. Allen, T. Zhou, and D. G. McMahon Gastrin-Releasing Peptide Mediates Light-Like Resetting of the Suprachiasmatic Nucleus Circadian Pacemaker through cAMP Response Element-Binding Protein and Per1 Activation J. Neurosci., October 31, 2007; 27(44): 12078 - 12087. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-L. To, M. A. Henson, E. D. Herzog, and F. J. Doyle III A Molecular Model for Intercellular Synchronization in the Mammalian Circadian Clock Biophys. J., June 1, 2007; 92(11): 3792 - 3803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Sheward, E. S. Maywood, K. L. French, J. M. Horn, M. H. Hastings, J. R. Seckl, M. C. Holmes, and A. J. Harmar Entrainment to Feeding but Not to Light: Circadian Phenotype of VPAC2 Receptor-Null Mice J. Neurosci., April 18, 2007; 27(16): 4351 - 4358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. I. Said, S. A. Hamidi, K. G. Dickman, A. M. Szema, S. Lyubsky, R. Z. Lin, Y.-P. Jiang, J. J. Chen, J. A. Waschek, and S. Kort Moderate Pulmonary Arterial Hypertension in Male Mice Lacking the Vasoactive Intestinal Peptide Gene Circulation, March 13, 2007; 115(10): 1260 - 1268. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Brown, C. S. Colwell, J. A. Waschek, and H. D. Piggins Disrupted Neuronal Activity Rhythms in the Suprachiasmatic Nuclei of Vasoactive Intestinal Polypeptide-Deficient Mice J Neurophysiol, March 1, 2007; 97(3): 2553 - 2558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Welsh VIP Activates and Couples Clock Cells. Focus on "Disrupted Neuronal Activity Rhythms in the Suprachiasmatic Nucleus of Vasoactive Intestinal Polypeptide-Deficient Mice" J Neurophysiol, March 1, 2007; 97(3): 1885 - 1886. [Full Text] [PDF]
|
|
|
|
|
|
M. C. Antle, N. C. Foley, D. K. Foley, and R. Silver Gates and Oscillators II: Zeitgebers and the Network Model of the Brain Clock J Biol Rhythms, February 1, 2007; 22(1): 14 - 25. [Abstract] [PDF]
|
|
|
|
 |
|
 E. S. Maywood, J. S. O'Neill, A. B. Reddy, J. E. Chesham, H. M. Prosser, C. P. Kyriacou, S. I. H. Godinho, P. M. Nolan, and M. H. Hastings Genetic and Molecular Analysis of the Central and Peripheral Circadian Clockwork of Mice Cold Spring Harb Symp Quant Biol, January 1, 2007; 72(0): 85 - 94. [Abstract] [PDF]
|
|
|
|
|
|
S. J. Kuhlman and D. G. McMahon Encoding the Ins and Outs of Circadian Pacemaking. J Biol Rhythms, December 1, 2006; 21(6): 470 - 481. [Abstract] [PDF]
|
|
|
|
 |
|
 A. M. Szema, S. A. Hamidi, S. Lyubsky, K. G. Dickman, S. Mathew, T. Abdel-Razek, J. J. Chen, J. A. Waschek, and S. I. Said Mice lacking the VIP gene show airway hyperresponsiveness and airway inflammation, partially reversible by VIP Am J Physiol Lung Cell Mol Physiol, November 1, 2006; 291(5): L880 - L886. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Brown, A. T. Hughes, and H. D. Piggins Gastrin-Releasing Peptide Promotes Suprachiasmatic Nuclei Cellular Rhythmicity in the Absence of Vasoactive Intestinal Polypeptide-VPAC2 Receptor Signaling J. Neurosci., November 30, 2005; 25(48): 11155 - 11164. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Lundkvist, Y. Kwak, E. K. Davis, H. Tei, and G. D. Block A Calcium Flux Is Required for Circadian Rhythm Generation in Mammalian Pacemaker Neurons J. Neurosci., August 17, 2005; 25(33): 7682 - 7686. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. C. Antle, L. J. Kriegsfeld, and R. Silver Signaling within the Master Clock of the Brain: Localized Activation of Mitogen-Activated Protein Kinase by Gastrin-Releasing Peptide J. Neurosci., March 9, 2005; 25(10): 2447 - 2454. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. S. Colwell, S. Michel, J. Itri, W. Rodriguez, J. Tam, V. Lelievre, Z. Hu, and J. A. Waschek Selective deficits in the circadian light response in mice lacking PACAP Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1194 - R1201. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Hastings and E. D. Herzog Clock Genes, Oscillators, and Cellular Networks in the Suprachiasmatic Nuclei J Biol Rhythms, October 1, 2004; 19(5): 400 - 413. [Abstract] [PDF]
|
|
|
|
|
|
J. Itri, S. Michel, J. A. Waschek, and C. S. Colwell Circadian Rhythm in Inhibitory Synaptic Transmission in the Mouse Suprachiasmatic Nucleus J Neurophysiol, July 1, 2004; 92(1): 311 - 319. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hannibal and J. Fahrenkrug Circadian rhythm regulation: a central role for the neuropeptide vasoactive intestinal polypeptide Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2003; 285(5): R935 - R936. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
