Developing Circadian Rhythmicity

THE CIRCADIAN TIMING SYSTEMCircadian rhythms are endogenously driven rhythms with a period length of approximately 24 hours that affect nearly every aspect of human physiologyP, 65, 66 Notable examples of circadian rhythms include the sleep-wake cycle and daily rhythms in hormone production.Circadian rhythms also are involved in the pathogenesis of many illnesses, such as reactive airway disease and myocardialThe system responsible for tlie generation and regulation of circadian rhythms is the circadian timing system.This neural system consists of a biologic clock, input pathways, and output pathways.67aThe paired suprachiasmatic nuclei (SCN) in the anterior hypothalamus are the site of a biologic clock.The SCN are located above the optic chiasm at the base of the third ventricleT9 (Fig. 1).The SCN exhibit endogenous rhythmicity and have a period of oscillation of approximately 24 hours.68Lesion studies in rodents provided the initial evidence that the SCN are the site of a circadian pacemaker.6zIn vivo and in vitro studies have since shown day-night rhythms in electric activity, metabolic activity, and gene expre~sion.~~,121, Transplantation of fetal SCN cells into SCN-lesioned animals restores rhythmicity to the recipient, further supporting that the SCN contain a biologic clock.nMost recently, circadian oscillations have been seen in individual rodent SCN cells.137