TIME-COURSE OF FIBER OUTGROWTH FROM FETAL ANTERIOR HYPOTHALAMIC HETEROGRAFTS

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.