The Human SCN in Health and Neuropsychiatric Disorders: Postmortem Observations

Abstract

The suprachiasmatic nucleus (SCN) is the master clock of the mammalian brain. Lesions in the human SCN region due to suprasellar pituitary tumors or metastasis result in a decreased expression of a major SCN peptide, arginine vasopressin (AVP), and in disturbed circadian rhythms. In Nissl-stained paraffin sections, the human SCN cannot be recognized without immunocytochemistry for AVP, vasoactive intestinal polypeptide (VIP), or neurotensin. Gamma-aminobutyric acid is co-localized with one or more peptides in SCN neurons. Compared to monkeys and other animals, the human SCN has very large populations of neurotensin cells and of neuropeptide Y neurons, which obscure a geniculo-hypothalamic tract containing the same peptide. In postmortem human SCN, distinct day–night and seasonal fluctuations were found for the AVP- and VIP-expressing neurons in subjects up to 50 years of age. Moreover, structural and functional differences in SCN are attributed to gender, sexual orientation, and sex differences in aging. The SCN drives circadian and circannual rhythms in the pineal gland production of melatonin that affects many brain functions mediated by the melatonin receptors (MT1 and MT2). Like the SCN, the pineal system also shows strong changes with aging. The retino-hypothalamic tract (RHT) directly innervates the VIP and neurotensin neurons in the SCN and mediates the entraining effects of light on the SCN. The RHT is made up of retinal ganglion cells, which contain pituitary adenylate cyclase-activating polypeptide (PACAP) and co-store glutamate. Light activates these cells via the photopigment melanopsin in the PACAP cells. In addition, serotonin and histamine innervate the SCN, while melatonin acting on the SCN is mediated by MT receptors. Immunocytochemical observations show that AVP and VIP fibers innervate the SCN itself, including the contralateral SCN and a number of other hypothalamic areas, including the sub-paraventricular zone and the dorsomedial nucleus. These observations match very well with the results of postmortem tracing following an injection into the human SCN. The strong projection from the SCN to the supraoptic nucleus seen in rodents was not found in human.