Suprachiasmatic nucleus

The suprachiasmatic nucleus (SCN) is a nucleus in the hypothalamus situated immediately above the optic chiasm, on either side of the third ventricle. The SCN generates a circadian rhythm of neuronal activity, which regulates many different body functions over a 24-hour period. The SCN contains several cell types, containing several different peptides (including vasopressin and vasoactive intestinal peptide) and neurotransmitters, and interacts with many other regions of the brain.

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. 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. 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. Rats with damage to the SCN sleep "erratically" (i.e., they do not follow the night-day rhythm).

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. The LGN passes information about color, contrast, shape, and movement on to the visual cortex. The superior colliculus controls the movement and orientation of the eyeball The pretectum controls the size of the pupil.

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.

For example, in the fruitfly Drosophila, the molecular clock in neurons is controlled by five genes, called clock (clk), cycle (cyc), period (per), cryptochrome (cry) and timeless (tim). These genes encode various transcription factors that trigger expression of other proteins. The products of clk and cyc, called CLK and CYC, form a heterodimer belonging to the PAS-containing subfamily of the basic-helix-loop-helix (bHLH) family of transcription factors. This heterodimer (CLK-CYC) upregulates the expression of PER, CRY, TIM, which then interfere with 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 mammals, homologs of the Drosophila circadian clock genes behave in a similar manner. BMAL-1 (brain and muscle aryl hydrocarbon receptor nuclear translocator (ARNT)-like 1) is the primary homolog of dCYC, and CLOCK bears the same name. Three homologs of PER have been identified (PER1-3) and two CRY homologs (CRY1,2). The cryptochromes also seem to respond to light-entrainment, allowing the day-night cycle to reset the circadian 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 as cocaine (PMID 16094306, PMID 16288309).

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.

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.