Vasoactive Intestinal Polypeptide Mediates Circadian Rhythms in Mammalian Olfactory Bulb and Olfaction

Abstract

Accumulating evidence suggests that the olfactory bulbs (OBs) function as an independent circadian system regulating daily rhythms in olfactoryperformance.However,thecellsandsignalsintheolfactorysystemthatgenerateandcoordinatethesecircadianrhythmsareunknown. 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.

Genome-Wide Screen Reveals Rhythmic Regulation of Genes Involved in Odor Processing in the Olfactory Epithelium

“…Additionally, online bioluminescence measurements in OE tissue explants displayed rhythmic PER2 expression patterns over several days. This is in agreement with observations in other peripheral tissues, which oscillate over the course of several days (Yoo et al, 2004) and with findings from OE explants recently reported by Miller et al (2014). In further support of an OE clock, we demonstrated that PER2 protein is expressed rhythmically ex vivo and displays circadian variation in cell bodies and dendritic knobs of OSNs.…”

Protein sequestration versus Hill‐type repression in circadian clock models

“…In particular, in plants, the core transcriptional NFL consists of series of transcriptional repressions, which has a similar design as the repressilator or quadripressilator [5,[171][172][173]. While the detailed transcriptional repression mechanism has not been fully identified, currently models have assumed Hill-type repression [171,[174][175][176][177].…”

Synchrony and desynchrony in circadian clocks: impacts on learning and memory

“…Structural evidence for synaptic scaling comes from Drosophila in which decreased synapse number and size may be observed after sleep (Bushey et al 2011 At the molecular level, circadian modulation of memory could occur at multiple levels through regulation of sensory gating, neurotransmission, kinase signaling cascades, macromolecular synthesis, or epigenetic modifications. Circadian gating of sensory processes, as observed for olfaction in insects (Krishnan et al 1999) and mammals (Granados-Fuentes et al 2006;Miller et al 2014), could alter salience and perception of sensory stimuli resulting in differential learning acquisition. Downstream, molecular processes can serve as a bridge between the circadian clock and memory either through circadian regulation of basal expression and activity levels, rhythms in cellular compartmentalization, or rhythms in training-inducible activity or expression (Table 1).…”

“…This hierarchy stands in contrast to the circadian system in lower vertebrates such as fish or invertebrates, e.g., Drosophila melanogaster, in which independently entrainable oscillators may be found throughout the organism (Plautz et al 1997;Whitmore et al 2000). Nonetheless, even in mammals independent peripheral oscillators exist including the food-entrainable oscillator in the liver (Stephan 2002;Saper and Fuller 2007;Mistlberger 2011) and oscillators in the olfactory bulb (Granados-Fuentes et al 2004;Abraham et al 2005;Miller et al 2014). …”