The suprachiasmatic nucleus or nuclei, abbreviated SCN, is a tiny region on the brain's midline, 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. The SCN, which is pine cone-shaped and the size of a grain of rice, interacts with many other regions of the brain. It contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters. Location The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or superior (hence supra) to the optic chiasm (CHO) bilateral to (on either side of) the third ventricle. Circadian effects 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 SCN receives inputs from specialized photosensitive ganglion cells in the retina, via the retinohypothalamic tract. Neurons in the ventrolateral SCN (vlSCN) have the ability for light-induced gene expression. Melanopsin-containing ganglion cells in the retina have a direct connection to the ventrolateral SCN via the retinohypothalamic tract. If light is turned on at night, the vlSCN relays this information throughout the SCN, in a process called entrainment. 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). A GABAergic mechanism couples the ventral and dorsal regions of the SCN. The SCN sends information to other hypothalamic nuclei and the pineal gland to modulate body temperature and production of hormones such as cortisol and melatonin. Circadian rhythms of endothermic and ectothermic vertebrates Information about the direct neuronal regulation of metabolic processes and circadian rhythm-controlled behaviors is not well known among either endothermic or ectothermic vertebrates, although extensive research has been done on the SCN in model animals such as the mammalian mouse and ectothermic reptiles, particularly lizards. The SCN is known to be involved not only in photoreception through innervation from the retinohypothalamic tract, but also in thermoregulation of vertebrates capable of homeostasis, as well as regulating locomotion and other behavioral outputs of the circadian clock within ectothermic vertebrates. The behavioral differences between both classes of vertebrates, when compared to the respective structures and properties of the SCN and various other nuclei proximate to the hypothalamus, provide insight into how these behaviors are the consequence of differing circadian regulation. Ultimately, many neuroethological studies must be done to completely ascertain the direct and indirect roles of the SCN on circadian-regulated behaviors of vertebrates. The SCN of endotherms and ectotherms Generally, external temperature does not influence endothermic animal behavior or circadian rhythm because of the ability of these animals to keep their internal body temperature constant through homeostatic thermoregulation; however, peripheral oscillators in mammals are sensitive to temperature pulses and will experience resetting of the circadian clock phase and associated genetic expression, suggesting how peripheral circadian oscillators may be separate entities from one another despite having a master oscillator within the SCN. Furthermore, when individual neurons of the SCN from a mouse were treated with heat pulses, a similar resetting of oscillators was observed, but when an intact SCN was treated with the same heat pulse treatment the SCN was resistant to temperature change by exhibiting an unaltered circadian oscillating phase. In ectothermic animals, particularly the ruin lizard Podacris sicula, temperature has been shown to affect the circadian oscillators within the SCN. This reflects a potential evolutionary relationship among endothermic and ectothermic vertebrates, in how ectotherms rely on environmental temperature to affect their circadian rhythms and behavior and endotherms have an evolved SCN to essentially ignore external temperature and use photoreception as a means for entraining the circadian oscillators within their SCN. Additionally, the differences of the SCN between endothermic and ectothermic vertebrates suggest that the neuronal organization of the temperature-resistant SCN in endotherms is responsible for driving thermoregulatory behaviors in those animals differently from those of ectotherms, since they rely on external temperature for engaging in certain behaviors. Behaviors controlled by the SCN of vertebrates Significant research has been conducted on the genes responsible for controlling circadian rhythm, particularly within the SCN. Knowledge of the gene expression of Clock (Clk) and Period2 (Per2), two of the many genes responsible for regulating circadian rhythm within the individual cells of the SCN, has allowed for a greater understanding of how genetic expression influences the regulation of circadian rhythm-controlled behaviors. 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. Certain findings have reflected how evolution of SCN both structurally and genetically has resulted in both classes of vertebrates engaging in characteristic and stereotyped thermoregulatory behavior. Other Signals from the Retina The SCN is one of many nuclei that receive nerve signals directly from the retina. Some of the others are the lateral geniculate nucleus (LGN), the superior colliculus, the basal optic system, and the pretectum: The LGN passes information about color, contrast, shape, and movement on to the visual cortex and itself signals to the SCN. The superior colliculus controls the movement and orientation of the eye. The basal optic system also controls eye movements. The pretectum controls the size of the pupil.