Brain: Suprachiasmatic nucleus
Suprachiasmatic nucleus is 'SC', at center left, in blue. OC, in black, is optic chiasm.
The left optic nerve and the optic tracts. (Suprachiasmatic nucleus not labeled, but diagram illustrates region.)
Latin	nucleus suprachiasmaticus
NeuroNames	hier-367
MeSH	Suprachiasmatic+Nucleus
Dorlands/Elsevier	n_11z/12583563

The suprachiasmatic nucleus (SCN) is a region of the brain, located in the hypothalamus, that is responsible for controlling endogenous circadian rhythms. The neuronal and hormonal activities it generates regulate many different body functions over a 24-hour period. Image File history File links Download high-resolution version (769x603, 447 KB) Hypothalamic Nuclei File links The following pages on the English Wikipedia link to this file (pages on other projects are not listed): Hypothalamus Supraoptic nucleus Paraventricular nucleus Suprachiasmatic nucleus Arcuate nucleus Median eminence Ventromedial nucleus Posterior nucleus (hypothalamus... Visual pathway with optic chiasm circled The optic chiasm (from the Greek χλαζειν to mark with an X, after the letter Χ chi) is the part of the brain where the optic nerves partially cross, those parts of the right eye which see things on the right side being connected to the... Image File history File links Gray773. ... For other uses, see Latin (disambiguation). ... NeuroNames is a system of nomenclature for the brain and related structures. ... Medical Subject Headings (MeSH) is a huge controlled vocabulary (or metadata system) for the purpose of indexing journal articles and books in the life sciences. ... Elseviers logo. ... The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... The Circadian rhythm is a name given to the internal body clock that regulates the (roughly) 24 hour cycle of biological processes in animals and plants. ...

The SCN contains several cell types and several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters, and interacts with many other regions of the brain. Peptides (from the Greek πεπτος, digestible), are the family of short molecules formed from the linking, in a defined order, of various α-amino acids. ... Arginine vasopressin (AVP), also known as argipressin or antidiuretic hormone (ADH), is a human hormone that is released when the body is low on water; it causes the kidneys to conserve water, but not salt, by concentrating the urine and reducing urine volume. ... VIP is a peptide hormone containing 28 amino acid residues. ... Chemical structure of D-aspartic acid, a common amino acid neurotransmitter. ...

Location

The SCN is situated in the hypothalamus immediately above the optic chiasm on either side of the third ventricle. The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). ... Visual pathway with optic chiasm circled The optic chiasm (from the Greek χλαζειν to mark with an X, after the letter Χ chi) is the part of the brain where the optic nerves partially cross, those parts of the right eye which see things on the right side being connected to the... The third ventricle is one of the four connected fluid-filled cavities within the human brain. ...

Circadian effects

The SCN receives inputs from specialized photoreceptive retinal ganglion cells, via the retinohypothalamic tract. A Ganglion Cell (or sometimes called a gangliocyte) is a type of Neuron located in the retina that receives visual information from bipolar cells; its axons give rise to the optic nerve. ... The Retinohypothalamic tract (RHT) is a photic input pathway involved in circadian rhythms. ...

Destruction of the SCN leads to a complete loss of circadian rhythm. Rats with damage to the SCN have no circadian rhythms, i.e., they sleep the same total amount, but at random times, for random lengths at a time. A circadian rhythm is a roughly-24-hour cycle in the physiological processes of living beings, including plants, animals, fungi and cyanobacteria. ...

The SCN also controls 'slave oscillators' in the peripheral tissues, which exhibit their own ~24 hour rhythms, but are crucially synchronized by the SCN.

The importance of entraining our bodies to an exogenous cue, such as light is reflected by several circadian rhythm sleep disorders, where this process does not function normally. Circadian rhythm sleep disorders are a family of sleep disorders affecting the timing of sleep. ...

Neurons in the ventrolateral SCN (vlSCN) have the ability for light-induced gene expression. If light is turned on at night, the vlSCN relays this information throughout the SCN, in a process called entrainment. Entrainment is the process whereby two interacting oscillating systems, which have similar periods when they function independently, assume the same period. ...

Neurons in the dorsomedial SCN (dmSCN) are believed to make an endogenous 24-hour rhythm that can persist under constant darkness (in humans averaging about 24h 11min). Melanopsin-containing ganglion cells in the retina have a direct connection to the SCN via the retino-hypothalamic tract. Melanopsin is a photopigment found in specialized ganglion cells of the retina that are involved in the regulation of circadian rhythms and pupillary reflex. ... A ganglion cell (or sometimes called a gangliocyte) is a type of neuron located in the retina that receives visual information from photoreceptors via various intermediate cells such as bipolar cells, amacrine cells, and horizontal cells. ... Human eye cross-sectional view. ...

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. The pineal gland (also called the pineal body or epiphysis) is a small endocrine gland in the brain. ... Cortisol is a corticosteroid hormone produced by the adrenal cortex (in the adrenal gland). ... Melatonin, 5-methoxy-N-acetyltryptamine, is a hormone found in all living creatures from algae[1] to humans, at levels that vary in a diurnal cycle. ...

Other signals from the retina

The SCN is one of four nuclei that receive nerve signals directly from the retina.

The other three are the lateral geniculate nucleus (LGN), the superior colliculus, and the pretectum: Grays FIG. 719– Hind- and mid-brains; postero-lateral view. ... The superior colliculus is part of the brain that sits below the thalamus and surrounds the pineal gland in the mesencephalon of vertebrate brains. ... Pretectum is a structure located in the forebrain. ...

• 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 eyeball.

• The pretectum controls the size of the pupil.

Brodmann area 17 (primary visual cortex) is shown in red in this image which also shows area 18 (orange) and 19 (yellow) The visual cortex refers to the primary visual cortex (also known as striate cortex or V1) and extrastriate visual cortical areas such as V2, V3, V4, and V5. ... The human eye The pupil is the central transparent area (showing as black). ...

Gene expression

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 is essentially similar in cells from many widely different organisms that show circadian rhythms. Gene expression, or simply expression, is the process by which the inheritable information which comprises a gene, such as the DNA sequence, is made manifest as a physical and biologically functional gene product, such as protein or RNA. Several steps in the gene expression process may be modulated, including the...

Fruitfly

For example, in the fruitfly Drosophila, the cellular circadian rhythm in neurons is controlled by two interlocked feedback loops. Type species Drosophila funebris (Fabricius, 1787) Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called fruit flies, or more appropriately vinegar flies, wine flies, pomace flies, grape flies, and picked fruit-flies, a reference to the characteristic of many species to linger...

• In the first loop, the bHLH transcription factors clock (clk) and cycle (cyc) drive the transcription of their own repressors period (per) and timeless (tim). PER and TIM proteins then accumulate in the cytoplasm, translocate into the nucleus at night, and turn off their own transcription, thereby setting up a 24 hour oscillation of transcription and translation.
• In the second loop, the transcription factors vrille (vri) and Pdp1 are initiated by CLK/CYC. PDP1 acts positively on Clk transcription and negatively on VRI.

These genes encode various transcription factors that trigger expression of other proteins. The products of clock and cycle, called CLK and CYC, belong to the PAS-containing subfamily of the basic-helix-loop-helix (bHLH) family of transcription factors, and form a heterodimer . This heterodimer (CLK-CYC) initiates the transcription of per and tim, whose protein products dimerize and then inhibit their own expression by disrupting CLK-CYC-mediated transcription. This negative feedback mechanism gives a 24-hour rhythm in the expression of the clock genes. Many genes are suspected to be linked to circadian control by "E-box elements" in their promoters, as CLK-CYC and its homologs bind to these elements. In the context of genetics, a transcription factor is a regulatory protein that initiates the transcription of certain genes upon binding with DNA. The binding of a transcription factor to a specific DNA sequence can result in either an increased rate of transcription of the gene, known as activated transcription... Why doesnt this site have bhlh on it? its got really dumb sites but none about bhlh or hlh. ... In the context of genetics, a transcription factor is a regulatory protein that initiates the transcription of certain genes upon binding with DNA. The binding of a transcription factor to a specific DNA sequence can result in either an increased rate of transcription of the gene, known as activated transcription... Sucrose, or common table sugar, is composed of glucose and fructose. ...

The 24-hr rhythm could be a monkey reset by light via the protein CRYPTOCHROME (CRY), which is involved in the circadian photoreception in Drosophila. CRY associates with TIM in a light-dependent manner that leads to the destruction of TIM. Without the presence of TIM for stabilization, PER is eventually destroyed during the day. As a result, the repression of CLK-CYC is reduced and the whole cycle reinitiates again.

Mammals

In mammals, circadian clock genes behave in a similar manner.

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. For other uses, see Clock (disambiguation). ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Aryl hydrocarbon receptor nuclear translocator-like, also known as ARNTL, Bmal1, or Mop3, is a gene. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Aryl hydrocarbon receptor nuclear translocator-like, also known as ARNTL, Bmal1, or Mop3, is a gene. ...

Three homologs of PER (PER1, PER2, and PER3) and two CRY homologs (CRY1 and CRY2) have been identified. Period (per) is a gene in Drosophilia which encodes a protein, PER, regulating circadian rhythm. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Period homolog 1 (Drosophila), also known as PER1, is a human gene. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Period homolog 2 (Drosophila), also known as PER2, is a human gene. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Period homolog 3 (Drosophila), also known as PER3, is a human gene. ... Cry may refer to: The mammalian behavior that brings about tears Usually an expression of a sad emotion A song, from an album of the same name, released in 2002 by the band Simple Minds A single released in 2002 by American pop artist Mandy Moore This is a disambiguation... Expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Cryptochrome 1 (photolyase-like), also known as CRY1, is a human gene. ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Cryptochrome 2 (photolyase-like), also known as CRY2, is a human gene. ...

TIM has been identified in mammals, however, its function is still not determined. Timeless (tim) is a gene in Drosophilia which encodes a protein, TIM, that regulates circadian rhythm. ...

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 as cocaine.^[1][2] Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. ...

Electrophysiology

Neurons in the SCN fire action potentials in a 24-hour rhythm. At mid-day, the firing rate reaches a maximum, and, during the night, it falls again. How the gene expression cycle (so-called the core clock) connects to the neural firing remains unknown. A. A schematic view of an idealized action potential illustrates its various phases as the action potential passes a point on a cell membrane. ...

Many SCN neurons are sensitive to light stimulation via the retina, and sustainedly firing action potentials during a light pulse (~30 seconds) in rodents. The photic response is likely linked to effects of light on circadian rhythms. In addition, focal application of melatonin can decrease firing activity of these neurons, suggesting that melatonin receptors present in the SCN mediate phase-shifting effects through the SCN.

Calcium dynamics

Two contradictory reports exist about circadian variation of the cell calcium concentration. However, both reports agree that the resting calcium level is slightly higher during the day than at night.

See also

• Chronobiology
• Sense of time

Chronobiology is a field of science that examines periodic (cyclic) phenomena in living organisms. ... Although the sense of time is not associated with a specific sensory system, the work of psychologists and neuroscientists indicates that our brains do have a system governing the perception of time. ...

References

1. ^ Yuferov V, Butelman E, Kreek M (2005). "Biological clock: biological clocks may modulate drug addiction". Eur J Hum Genet 13 (10): 1101-3. PMID 16094306. 
2. ^ Manev H, Uz T (2006). "Clock genes as a link between addiction and obesity". Eur J Hum Genet 14 (1): 5. PMID 16288309. 

External links

• Diagram at thebrain.mcgill.ca