Olfactory stimulation enhances light-induced phase shifts in free-running activity rhythms and Fos expression in the suprachiasmatic nucleus

Abstract

There is evidence to suggest that the olfactory and circadian systems are linked, functionally, and that olfactory stimuli can modulate circadian rhythms in mammals. Furthermore, olfactory bulb removal can alter free-running rhythms in animals housed in constant darkness and can attenuate the effect of social stimuli on photic entrainment of circadian rhythms. The mechanisms through which olfactory stimuli influence circadian rhythms are not known. One possibility is that olfactory stimuli influence circadian rhythms by modulating the activity of the circadian clock located in the hypothalamic suprachiasmatic nucleus. To study this, we assessed the effect of olfactory stimulation on free-running rhythms and on photic resetting of the circadian clock in rats using phase shifts in wheel-running rhythms and expression of the transcription factor Fos in the suprachiasmatic nucleus. We found that brief exposure to an olfactory stimulus, cedar wood essence, in the subjective day or subjective night had no effect on either free-running rhythms or Fos expression in the suprachiasmatic nucleus, but that when presented in combination with light, the odor dramatically enhanced light-induced phase shifts and Fos expression in the suprachiasmatic nucleus. Olfactory stimulation alone induced Fos expression in several structures that innervate the suprachiasmatic nucleus, pointing to ways by which stimulus information transmitted in the olfactory pathways could gain access to the suprachiasmatic nucleus to modulate photic resetting. These findings, showing that clock resetting by light can be facilitated by olfactory stimulation, point to a mechanism by which olfactory cues can modulate entrainment of circadian rhythms.