The suprachiasmatic nucleus or nuclei (SCN) is a small region of the brain in the hypothalamus, situated directly above the optic chiasm. It is responsible for regulating sleep cycles in animals. 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. The neuronal and hormonal activities it generates regulate many different body functions in an approximately 24-hour cycle. The SCN also interacts with many other regions of the brain. It contains several cell types, neurotransmitters and peptides, including vasopressin and vasoactive intestinal peptide. Disruptions or damage to the SCN has been associated with different mood disorders and sleep disorders, suggesting the significance of the SCN in regulating circadian timing.
Neuroanatomy The SCN is situated in the anterior part of the hypothalamus immediately dorsal, or superior (hence supra) to the optic chiasm bilateral to (on either side of) the third ventricle. It consists of two nuclei composed of approximately 10,000 neurons. The morphology of the SCN is species dependent. Distribution of different cell phenotypes across specific SCN regions, such as the concentration of VP-IR neurons, can cause the shape of the SCN to change. The nucleus can be divided into ventrolateral and dorsolateral portions, also known as the core and shell, respectively. These regions differ in their expression of the clock genes, the core expresses them in response to stimuli whereas the shell expresses them constitutively. In terms of projections, the core receives innervation via three main pathways, the retinohypothalamic tract, geniculohypothalamic tract, and projections from some raphe nuclei. The dorsomedial SCN is mainly innervated by the core and also by other hypothalamic areas. 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. The most abundant peptides found within the SCN are arginine-vasopressin (AVP), vasoactive intestinal polypeptide (VIP), and peptide histidine-isoleucine (PHI). Each of these peptides are localized in different regions. Neurons with AVP are found dorsomedially, whereas VIP-containing and PHI-containing neurons are found ventrolaterally.
Circadian clock
Different organisms such as bacteria, plants, fungi, and animals, show genetically based near-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. Many aspects of mammalian behavior and physiology show circadian rhythmicity, including sleep, physical activity, alertness, hormone levels, body temperature, immune function, and digestive activity. Early experiments on the function of the SCN involved lesioning the SCN in hamsters. SCN lesioned hamsters lost their daily activity rhythms. Further, when the SCN of a hamster was transplanted into an SCN lesioned hamster, the hamster adopted the rhythms of the hamster from which the SCN was transplanted. Together, these experiments suggest that the SCN is sufficient for generating circadian rhythms in hamsters. Later studies have shown that skeletal, muscle, liver, and lung tissues in rats generate 24-hour rhythms, which dampen over time when isolated in a dish, where the SCN maintains its rhythms. Together, these data suggest a model whereby the SCN maintains control across the body by synchronizing "slave oscillators," which exhibit their own near-24-hour rhythms and control circadian phenomena in local tissue. The SCN receives input 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. 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. 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. 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 is involved in the coupling of the ventral and dorsal regions of the SCN.
Circadian rhythms of endothermic (warm-blooded) and ectothermic (cold-blooded) 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 homeothermy 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 as well as 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.
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