Vasopressin (VP) neurons removed from normal fetal donors survive transplantation to the hypothalamic third ventricle of adult Brattleboro rats that congenitally lack VP neurons (DI rats). Amelioration of the symptoms of diabetes insipidus indicates that the grafted neurons become functionally integrated with the host. The proposed experiments are designed to elucidate the specific vascular and neural connections established between the host brain and the transplants that underlie the observed recovery of function. VP-containing fetal hypothalamin will be transplanted to the third ventricle and other sites within the central nervous system (CNS) of adult DI rats. The capacity of these grafts to relieve deficiencies in water homeostasis will be assessed prior to anatomical experiments. The pattern of revascularization established within the transplants and efferent connections of the grafted neurons with the host systemic circulation will be examined. This will be accomplished by infusing horseradish peroxidase or ink into the host's circulatory system. Afferent and efferent neural connections between the transplant and the host CNS will be studied by placing micro-injections of anterograde or retrograde tracers into the transplant or the host brain, particularly intothose areas that normally innervate VP neurons. In addition to defining some of the structrural correlates of functional recovery in this model system, these experiments should enhance our understanding of fundamental principles regulating the establishment of appropriate neural connections. This, in turn, may aid in the development of neural graft systems for alleviating neurological deficits resulting from other types of CNS damage or disease.
