Functional development of fetal suprachiasmatic nucleus grafts in suprachiasmatic nucleus-lesioned rats

Recovery of circadian drinking rhythms in suprachiasmatic nucleus (SCN)-lesioned rats after fetal SCN grafting was related to the immunocytochemical appearance and fiber outgrowth of vasopressin (VP)-, vasoactive intestinal polypeptide (VIP)-, and somatostatin (SOM)-containing neurons in the implants. At 4 weeks postgrafting, the first recovered animal was found. After longer survival times, 38% of the animals showed recovery. Immunocytochemical evaluation indicated that full maturation of the SCN grafts was not reached until 4 weeks postgrafting. Grafted VP and VIP cells were always located together, whereas SOM cells were clustered nearby but separate. Neuropeptide Y fibers were observed with an increasing fiber density between 2 and 5 weeks posttransplantation and were clustered particularly at the level of the SOM cells. In all rhythm-recovered animals transplants of VP and VIP fibers had grown laterally into the hypothalamus. A few nonrecovered animals also showed ingrowth of such fibers, though more caudally to the lesioned SCN. Many of the nonrecovered rats showed similar stainings but without these efferent outgrowth to the host. We conclude that neither a humoral factor nor the presence of VP and VIP efferents in the host brain alone are enough for the restoration of circadian drinking rhythms.