Introduction to Circadian Rhythms and Mechanisms of Circadian Oscillations

Abstract

Circadian rhythms are rhythms in behavior, physiology, or metabolism with a cycle length of approximately 24 h. Environmental disruption of daily rhythms leads to adverse health consequences, both in animal models and in humans engaged in shift work. The light–dark cycle has a major “entraining” influence on rhythms. Light for circadian entrainment is detected by rods, cones, and a population of intrinsically photosensitive retinal ganglion cells. The suprachiasmatic nuclei (SCN) generate and regulate circadian rhythms. SCN neurons coordinate their oscillations through several neurotransmitters and impact downstream neural structures by rhythmic neuronal firing. The molecular mechanism for circadian oscillation is a transcriptional–translational feedback loop that cycles with ~24 h periodicity in SCN neurons and also in other cell types. Many tissues maintain circadian oscillations even when isolated in vitro. Mechanisms by which the SCN coordinate these peripheral oscillators include rhythmic body temperature, food intake, and hormones. The molecular oscillator includes transcription factors, negative regulators, kinases, transcriptional co-activators and co-repressors, and posttranslational modifications to histone proteins. Several of these processes are influenced by metabolic factors. Several mutant mouse models are available for circadian rhythm research. While most data fit within the framework emphasized here, some “inconvenient truths” exist: under some circumstances, the SCN are not necessary for behavioral rhythms (with oscillations occurring by genetic mechanisms distinct from those discussed above), and in fact circadian oscillations can occur in the absence of transcription. Despite great progress in revealing circadian mechanisms over the past 20 years, much remains to be learned about circadian clocks.