The European journal of neuroscienceFeb 26, 2010

How the brain chemicals PACAP and VIP help light control gene activity in the body's internal clock

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

Loss of vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase-activating polypeptide (PACAP) significantly alters the circadian response to light in mice.

Mice lacking VIP or PACAP show reduced light-induced activation of certain brain cells during the subjective night.
The clock gene Period1 (Per1) is less activated by light in VIP-deficient mice, but not in PACAP-deficient mice.
During the subjective day, VIP-deficient mice exhibit increased levels of light-induced markers, differing from other genotypes.
Baseline levels of FOS, p-MAPK, and Per1 remain unchanged at night in the absence of VIP or PACAP.
Both neuropeptides are linked to the regulation of how the brain's circadian system responds to light exposure.

Simplified

Previously, we have shown that mice deficient in either vasoactive intestinal peptide (VIP) or pituitary adenylate cyclase-activating polypeptide (PACAP) exhibit specific deficits in the behavioral response of their circadian system to light. In this study, we investigated how the photic regulation of the molecular clock within the suprachiasmatic nucleus (SCN) is altered by the loss of these closely-related peptides. During the subjective night, the magnitude of the light-induction of FOS and phosphorylated mitogen-activated protein kinase (p-MAPK) immunoreactive cells within the SCN was significantly reduced in both VIP- and PACAP-deficient mice when compared with wild-type mice. The photic induction of the clock gene Period1 (Per1) in the SCN was reduced in the VIP- but not in the PACAP-deficient mice. Baselines levels of FOS, p-MAPK or Per1 in the night were not altered by the loss of these peptides. In contrast, during the subjective day, light exposure increased the levels of FOS, p-MAPK and Per1 in the SCN of VIP-deficient mice, but not in the other genotypes. During this phase, baseline levels of these markers were reduced in the VIP-deficient mice compared with untreated controls. Finally, the loss of either neuropeptide reduced the magnitude of the light-evoked increase in Per1 levels in the adrenals in the subjective night without any change in baseline levels. In summary, our results indicate that both VIP and PACAP regulate the responsiveness of cells within the SCN to the effects of light. Furthermore, VIP, but not PACAP, is required for the appropriate temporal gating of light-induced gene expression within the SCN.

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How the brain chemicals PACAP and VIP help light control gene activity in the body's internal clock

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