Suprachiasmatic nucleus (SCN)

The suprachiasmatic nucleus (SCN) is a paired hypothalamic structure situated immediately above the optic chiasm, containing approximately 20,000 neurons per side. It functions as the master circadian pacemaker of mammals, generating a near-24-hour rhythm via an autoregulatory transcriptional-translational feedback loop involving CLOCK, BMAL1, PER, and CRY proteins. Photic input from intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing melanopsin entrains the SCN to the environmental light-dark cycle through the retinohypothalamic tract. The pacemaker role was definitively established by Ralph and colleagues (Science, 1990): grafting SCN tissue from a short-period mutant hamster into SCN-lesioned wild-type hosts restored circadian rhythms with the donor's period. SCN outputs synchronise peripheral clocks in liver, muscle, adipose, and other tissues via neural and humoral signals.