Animal experimental studies have shown that the retinohypothalamic tra
ct (RHT) is an anatomical and functionally distinct retinofugal pathwa
y mediating photic entrainment of circadian rhythms. In the present st
udy, RHT projections were studied in the human brain by our recently d
eveloped postmortem tracing technique with neurobiotin as a tracer. Si
milar patterns of labeling were observed in brains of one control subj
ect without neurological! or mental disorders and five patients with A
lzheimer's disease. The topography of RHT projections has several char
acteristics. (1) RHT fibers leave the optic chiasm and enter the hypot
halamus medially and laterally at the anterior level of the suprachias
matic nucleus (SCN). (2) The medial fibers enter the ventral part of t
he SCN and innervate the ventral SCN over its entire length, but the d
ensity decreases gradually from anterior to posterior. Labeled RHT fib
ers in the SCN make contact mainly with immunocytochemically positive
neurotensin or vasoactive intestinal polypeptide neurons and only occa
sionally with vasopressin-positive neurons located in the ventral part
of the SCN. (3) Only few projections to the dorsal part of the SCN an
d the anteroventral part of the hypothalamus were found. (4) Lateral p
rojections reach the ventral part of the ventromedial SON and the area
lateral to the SCN. No projections were observed to other hypothalami
c areas. The presence of an RHT in humans suggests that the RHT may se
rve a function in humans similar to that demonstrated in animals. J. C
omp. Neurol. 397:357-370, 1998. (C) 1998 Wiley-Liss, Inc.