The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm.

[1][2] Reception of light inputs from photosensitive retinal ganglion cells allow it to coordinate the subordinate cellular clocks of the body and entrain to the environment.

Lastly, its output is mainly to the subparaventricular zone and dorsomedial hypothalamic nucleus which both mediate the influence SCN exerts over circadian regulation of the body.

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.

[12] When the retina receives light, the vlSCN relays this information throughout the SCN allowing entrainment, synchronization, of the person's or animal's daily rhythms to the 24-hour cycle in nature.

[12] 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.

[13] Neurons in the dorsomedial SCN (dmSCN) are believed to have an endogenous 24-hour rhythm that can persist under constant darkness (in humans averaging about 24 hours 11 min).

Ultimately, many neuroethological studies must be done to completely ascertain the direct and indirect roles of the SCN on circadian-regulated behaviors of vertebrates.

[17] This reflects a potential evolutionary relationship among endothermic and ectothermic vertebrates as ectotherms rely on environmental temperature to affect their circadian rhythms and behavior while endotherms have an evolved SCN that is resistant to external temperature fluctuations and uses photoreception as a means for entraining the circadian oscillators within their SCN.

[18] Studies on thermoregulation of ruin lizards and mice have informed some connections between the neural and genetic components of both vertebrates when experiencing induced hypothermic conditions.

[17] Certain findings have reflected how evolution of SCN both structurally and genetically has resulted in the engagement of characteristic and stereotyped thermoregulatory behavior in both classes of vertebrates.

These heterodimers then bind to E-boxes upstream of multiple genes, including per and cry, to enhance and promote their transcription and eventual translation.

In addition, application of melatonin in live rats and isolated SCN cells can decrease the firing rate of these neurons.

When SCN rhythms were disturbed, anxiety-like behavior, weight gain, helplessness, and despair were reported in a study conducted with mice.

[44] Patients with AD experience insomnia, hypersomnia, and other sleep disorders as a result of the degeneration of the SCN and changes in critical neurotransmitter concentrations.

[44] The idea that the SCN is the main sleep cycle regulator in mammals was proposed by Robert Moore, who conducted experiments using radioactive amino acids to find where the termination of the retinohypothalamic projection occurs in rodents.

[45][46] Early lesioning experiments in mouse, guinea pig, cat, and opossum established how removal of the SCN results in ablation of circadian rhythm in mammals.