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Disrupted circadian rhythms in VIP- and PHI-deficient mice
Abstract
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.
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Citations
Cites
Phototransduction by retinal ganglion cells that set the circadian clock
Berson, D. M., Dunn, F. A., & Takao, M. (2002) · Science · doi:10.1126/science.1067262 · Cited by 3,629
Cited by
Suprachiasmatic Nucleus: Cell Autonomy and Network Properties
Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135919 · Cited by 1,216
The circadian visual system, 2005
Morin, L. P., & Allen, C. N. (2006) · Brain Research Reviews · doi:10.1016/j.brainresrev.2005.08.003 · Cited by 784
Molecular components of the mammalian circadian clock
Buhr, E. D., & Takahashi, J. S. (2013) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-25950-0_1 · Cited by 738
Jones, S. E., Lane, J. M., Wood, A. R., van Hees, V. T., Tyrrell, J., Beaumont, R. N., Jeffries, A. R., Dashti, H. S., Hillsdon, M., Ruth, K. S., et al. (2019) · Nature Communications · doi:10.1038/s41467-018-08259-7 · Cited by 691
VPAC and PAC receptors: From ligands to function
Dickson, L., & Finlayson, K. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2008.11.006 · Cited by 379
Metadata
- Authors
- Colwell, C. S., Michel, S., Itri, J., Rodriguez, W., Tam, J., Lelievre, V., Hu, Z., Liu, X., & Waschek, J. A.
- Venue
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Publisher
- American Physiological Society
- Published
- 2003-11
- Volume
- 285
- Issue
- 5
- Pages
- R939-R949
- ISSN
- 0363-6119 (ISSN-L)
- 1522-1490
- OpenAlex
- W2129971651
- Cited by
- 392
- References
- 1
- FWCI
- 5.11
- Type
- journal article
- Language
- en
- Open access
- closed
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- Colwell, C. S., Michel, S., Itri, J., Rodriguez, W., Tam, J., Lelievre, V., Hu, Z., Liu, X., & Waschek, J. A. (2003). Disrupted circadian rhythms in VIP- and PHI-deficient mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. https://doi.org/10.1152/ajpregu.00200.2003
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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