The fourth C.U. Ariëns Kappers lecture. The organization of the human circadian timing system

The mammalian circadian timing system has three principal components; (1) photoreceptors and visual pathways mediating entrainment; (2) a pacemaker, the suprachiasmatic nucleus of the hypothalamus; and (3) efferent pathways coupling the suprachiasmatic nucleus to effector systems exhibiting circadian function. In most mammals there are two visual entraining pathways, a direct retinohypothalamic pathway terminating in the suprachiasmatic nucleus, for which the transmitter is unknown, and a secondary visual pathway, the geniculohypothalamic tract, from the intergeniculate leaflet of the lateral geniculate to the suprachiasmatic nucleus that is neuropeptide Y-producing. These pathways end in a distinct subdivision of the suprachiasmatic nucleus characterized by the presence of vasoactive intestinal polypeptide neurons. A second suprachiasmatic nucleus division does not receive visual afferents and is characterized by vasopressin neurons. The efferent projections of the suprachiasmatic nucleus are very restricted, predominantly to the hypothalamus. Although we have much less information on the human circadian timing system than on that of other animals, it seems clear that the human conforms to the general animal pattern in most features. There are, however, two significant differences. First, the largest neural component of the human suprachiasmatic nucleus is a population of neurotensin neurons found throughout the nucleus. Few, if any, neurotensin neurons are found in monkey or other mammals. Second, the human suprachiasmatic nucleus contains a large number of neuropeptide Y neurons located where the plexus arising from geniculate neuropeptide Y neurons is found in other mammals. This is unique and suggests that the geniculohypothalamic projection may be bypassed in the human. It also may imply that the functional organization of the human SCN is fundamentally different from that of other mammals. The function of the circadian timing system is to coordinate the activities of a series of homeostatic regulatory mechanisms with the control of behavioral state in a temporal pattern that facilitates adaptive behavior, including reproduction (Fig. 9). The function of this system, then, is to provide the appropriate physiological and behavioral background to facilitate adaptation and survival.