The suprachiasmatic nucleus or nuclei (SCN) is a tiny region located in the hypothalamus, situated directly above the optic chiasm. It is responsible for controlling circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions in a 24-hour cycle, using around 20,000 neurons. According to a study, the rat SCN tends to diminish in size with age.
The SCN interacts with many other regions of the brain. It contains several cell types and several different peptides (includingvasopressin and vasoactive intestinal peptide) and neurotransmitters.
Organisms in every kingdom of life—bacteria, plants, fungi, and animals—show genetically-based 24-hour rhythms. Although all of these clocks appear to be based on a similar type of genetic feedback loop, the specific genes involved are thought to have evolved independently in each kingdom. Within the animal kingdom, however, a related set of genes are used by a wide variety of animals: The circadian genes in fruit flies, for example, are closely related to those in mammals.
Many aspects of mammalian behavior and physiology show circadian rhythmicity, including sleep, physical activity, alertness, hormone levels, body temperature, immune function, and digestive activity. All of these diverse rhythms are controlled by a single tiny brain area, the SCN, and are lost if the SCN is destroyed. In the case of sleep, for example, the total amount is maintained in rats with SCN damage, but the length and timing of sleep episodes become erratic. The importance of entraining organisms, including humans, to exogenous cues such as the light/dark cycle, is reflected by several circadian rhythm sleep disorders, where this process does not function normally.
The SCN also controls “slave oscillators” in the peripheral tissues, which exhibit their own ~24-hour rhythms, but are kept in synchrony by the SCN.
The circadian rhythm in the SCN is generated by a gene expression cycle in individual SCN neurons. This cycle has been well conserved through evolution and in essence is similar in cells from many widely different organisms that show circadian rhythms.
In mammals, circadian clock genes behave in a manner similar to that of flies.
CLOCK (circadian locomotor output cycles kaput) was first cloned in mouse and BMAL1 (brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1) is the primary homolog of Drosophila CYC.
Three homologs of PER (PER1, PER2, and PER3) and two CRY homologs (CRY1 and CRY2) have been identified.
TIM has been identified in mammals; however, its function is still not determined. Mutations in TIM result in an inability to respond to zeitgebers, which is essential for resetting the biological clock.
Recent research suggests that, outside the SCN, clock genes may have other important roles as well, including their influence on the effects of drugs of abuse such ascocaine.