Postmortem tracing reveals the organization of hypothalamic projections of the suprachiasmatic nucleus in the human brain.

The suprachiasmatic nucleus (SCN) is a small structure considered to be the site of the major circadian pacemaker of the mammalian brain. Disturbances in human biological clock function may occur in several diseases, such as Alzheimer's disease, sleep problems, and seasonal depression. Since basic knowledge of the anatomical connections of the human SCN is limited due to the lack of suitable neuroanatomical tracing methods, the understanding of physiological mechanisms of human SCN function has obviously been hampered. In the present study, the hypothalamic connections of the human SCN were revealed for the first time with a newly developed in vitro postmortem anterograde tracing method. The human SCN was found to be connected with nuclei in the hypothalamus that are involved in hormone secretion, cardiovascular regulation, and behavior activity. These human SCN projections appear to follow the same general patterns as those in the rodent brain. This homology may indicate an evolutionary conservation of the SCN projections from rodent to human. Through these connections, the human SCN may transmit its circadian information to regulate hormone secretion, body temperature, and behavioral functions as it does in animal species. In addition, the postmortem tracing technique may be a valuable tool that will contribute to our understanding of anatomical connections in the human brain, and may have other applications in the research on the physiology and pathology of the human brain.