Fetal anterior hypothalamic (AH) heterografts can restore circadian rh
ythmicity to animals rendered arhythmic following ablation of the supr
achiasmatic nucleus (SCN). Behavioral restoration of circadian activit
y typically begins between two and six weeks post-implantation. The ti
me course of fiber outgrowth from fetal AH heterografts was examined t
o determine whether neuronal outgrowth from the implants precedes the
typically observed effects of such implants upon circadian behavior. F
etal mouse or rat AH tissue containing the SCN was implanted into the
third ventricle of SCN-lesioned hamsters. Using species-specific monoc
lonal antibodies generated against mouse or rat neuronal elements, fib
er outgrowth into the host hypothalamus was examined at 2, 4, 7, 14, 3
0 and 45 days after implantation. Fibers were observed to have emerged
from the implant at the earliest time point examined. Four days after
surgery, individual fibers had extended up to 0.6 mm into the host ne
uropil. By 14 days post-implantation, outgrowth from the implant had f
ormed a dense fiber plexus in the host hypothalamus. This observation
demonstrates that neuronal integration of the implant with the host br
ain begins within 48 hours of implantation, and is extensively establi
shed well before a restoration of rhythmicity is typically observed. T
hus, on the basis of the time course of fiber outgrowth, it is clear t
hat neuronal contact between graft and host may mediate the observed r
estoration of circadian rhythmicity.