Vasoactive intestinal polypeptide mediates circadian rhythms in mammalian olfactory bulb and olfaction.
Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactory performance. However, the cells and signals in the olfactory system that generate and coordinate these circadian rhythms are unknown. Using real-time imaging of gene expression, we found that the isolated olfactory epithelium and OB, but not the piriform cortex, express similar, sustained circadian rhythms in PERIOD2 (PER2). In vivo, PER2 expression in the OB of mice is circadian, approximately doubling with a peak around subjective dusk. Furthermore, mice exhibit circadian rhythms in odor detection performance with a peak at approximately subjective dusk. We also found that circadian rhythms in gene expression and odor detection performance require vasoactive intestinal polypeptide (VIP) or its receptor VPAC2R. VIP is expressed, in a circadian manner, in interneurons in the external plexiform and periglomerular layers, whereas VPAC2R is expressed in mitral and external tufted cells in the OB. Together, these results indicate that VIP signaling modulates the output from the OB to maintain circadian rhythms in the mammalian olfactory system.
Departments of Biology and Anatomy and Neurobiology, Washington University, St. Louis, Missouri 63130.
Jae-Eun Kang
JE
Miller
Daniel
D
Granados-Fuentes
Thomas
T
Wang
Luciano
L
Marpegan
Timothy E
TE
Holy
Erik D
ED
Herzog
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism; D002940:Circadian Rhythm / Q000502:physiology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D009830:Olfactory Bulb / Q000378:metabolism*; D009831:Olfactory Mucosa / Q000378:metabolism; D009833:Olfactory Pathways / Q000378:metabolism*; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D051239:Receptors, Vasoactive Intestinal Peptide, Type II / Q000235:genetics / Q000378:metabolism; D012903:Smell / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism*
C513312:Per2 protein, mouse; D056950:Period Circadian Proteins; D051239:Receptors, Vasoactive Intestinal Peptide, Type II; D014660:Vasoactive Intestinal Peptide
VIP; circadian; clock; olfaction; olfactory discrimination; rhythms