A Circadian Clock in the Olfactory Bulb Controls Olfactory Responsivity

Abstract

Recently, it has been shown that multiple mammalian cell types express daily rhythms in vitro. Although the suprachiasmatic nucleus (SCN) of the hypothalamus is known to regulate a wide range of circadian behaviors, the role for intrinsic rhythmicity in other tissues is unknown. We tested whether the main olfactory bulb (OB) of mice mediates daily changes in olfaction. We found circadian rhythms in cedar oil-induced c-Fos, a protein marker of cellular excitation, in the mitral and granular layers of the OB and in the piriform cortex (PC). These oscillations persisted in constant darkness with a fourfold change in amplitude and a peak ϳ4 h after the onset of daily locomotor activity. Electrolytic lesions of the SCN abolished circadian locomotor rhythms, but not odor-induced c-Fos rhythms in the OB or PC. Furthermore, removal of the OB abolished spontaneous circadian cycling of c-Fos in the PC, shortened the free-running period of locomotor rhythms, and accelerated re-entrainment after a 6 h advance and slowed re-entrainment after a 6 h delay in the light schedule. OB ablation or odorant altered the amplitude of c-Fos rhythms in the SCN and ablation of one OB abolished c-Fos rhythms in the ipsilateral PC, but not in the contralateral OB and PC. We conclude that the OB comprises a master circadian pacemaker, which enhances olfactory responsivity each night, drives rhythms in the PC, and interacts with the SCN to coordinate other daily behaviors.

Circadian regulation of olfaction and an evolutionarily conserved, nontranscriptional marker in Caenorhabditis elegans

“…As has been reported for other animals, we found daily oscillations in olfaction (19,29,40,48,49), suggesting that this sensory function has an important status in the circadian system. Regulation of olfaction by the circadian clock in nematodes has farreaching and ecologically important functions and is an indication of the adaptive nature of the clock in a dark-living animal, as they use olfaction to find appropriate food sources (34) and thus to orient themselves spatially in their environment.…”

“…Further, we show daily oscillations in a behavior, olfaction, under entrainment as well as in constant conditions. Olfaction is also clock-regulated in insects and mammals (19)(20)(21). Finally, we find rhythms in the amount of a key protein kinase that is involved in regulating olfaction in C. elegans, Drosophila, and mammals.…”

“…In seemingly all circadian systems, sensory functions are clockregulated. Olfaction, for example, is regulated by the circadian clock in many animals (19)(20)(21)29). Indeed, it is one of the most robust behaviors described in this nematode (30)(31)(32)(33) and is a key component of fitness, as it guides between nutritious and pathogenic food choices (34).…”

Circadian genes, rhythms and the biology of mood disorders

“…NPAS2 may also function in the place of CLOCK in the SCN if the CLOCK protein is genetically disrupted (Debruyne et al, 2006). Though the central circadian pacemaker is located in the SCN, all of these genes are expressed throughout the brain and in other organs where they function as peripheral clocks that respond to nonphotic stimuli, and likely in other processes unrelated to circadian rhythms (Abe et al, 2001;Stokkan et al, 2001;Iijima et al, 2002;Granados-Fuentes et al, 2006;McDearmon et al, 2006;Mieda et al, 2006).…”

The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks

“…Obviously, these observations are not readily compatible with the simplest version of a transcriptional/translational feedback loop model. Therefore, it must be the activity rather than the accumulation of core clock components The master clock in the brain's suprachiasmatic nuclei (in conjunction with daily oscillations in environmental factors) controls rest-activity cycles, circadian fluctuations of the cardiovascular system (heart beat frequency, blood pressure), body temperature, the endocrine system, renal activity, intestinal motility (Hoogerwerf 2010), and metabolism in organs such as liver, endocrine pancreas, adipose tissue, and muscle, as well as sensorial acuity (e.g., olfaction) (Granados-Fuentes et al 2006). The metabolism of xenobiotics (e.g., toxins ingested with food, medical drugs) in liver, kidney, and small intestine is also highly circadian.…”