Fiber outgrowth from anterior hypothalamic and cortical xenografts in the third ventricle

Fetal grafts of the anterior hypothalamus (SCN/AH) containing the suprachiasmatic nucleus (SCN) restore circadian rhythms to SCN-lesioned host hamsters and rats following implantation into the third ventricle. Previous studies suggest that intraventricular SCN/AH grafts are variable in their attachment sites, the extent of their outgrowth, and the precise targets innervated in the host brain. However, the use of different methods to analyze graft outgrowth in this model has previously led to inconsistent results. We have reevaluated the outgrowth of fetal rat SCN/AH grafts implanted in the third ventricle of hamsters by using two methods: the carbocyanine dye, 1,1'dioctadecyl-3,3'-tetramethylindocarbocyanine percholate (DiI), was placed directly onto grafted tissue; and a donor-specific neurofilament marker was used in conjunction with xenografts. We examined the specificity of outgrowth by comparing SCN/AH xenografts with that of control cortical (CTX) xenografts. To evaluate whether SCN/AH graft efferents arise from the donor SCN, we used micropunch grafts that contained minimal extra-SCN tissue. The results show that the use of a donor-specific neurofilament marker reveals more extensive SCN/AH graft outgrowth than DiI. SCN/AH graft efferents project into areas normally innervated by the intact SCN. However, this outgrowth is variable among graft recipients, is not specific to SCN/AH tissue, and does not necessarily derive from the donor SCN. The precise functional role of neural efferents arising from SCN/AH grafts in the restoration of circadian clock function and the extent of SCN-derived efferents remain to be determined.