The morphological, biochemical, and behavioral alterations resulting from MPTP produce a useful model, unique in non-human primates or studying cellular and molecular techniques for neural repair of the central nervous system. While some techniques have shown promise in our previous primate studies and in patients, major improvements appear possible and essential. This program proposes to continue to develop, characterize, and improve techniques for neural repair aimed at factors affecting the replacement cells and the host. The program also will explore basic neurobiological questions about the development and growth of dopaminergic neurons. The first project focuses on improving the techniques for survival of fetal neural cells, investigating effects of embryonic age, tissue preparation, pharmacologic manipulations, and growth factors. The second project investigates functional aspects of mesencephalic grafts, attempting to determine of the grafted cells are responsible for improvement, and, if so, is dopamine release by the grafts critical for functional effects. The third project will investigate host factors related to reconstructing physiologic connections due to subregional and distribution effects of graft placement in the large primate brain. All of these projects will be undertaken jointly by the program investigators, applying the resources of core units on morphology , biochemistry/pharmacology, behavior, and a primate transplantation laboratory, all coordinated by an administrative unit. Although the focus of this program is on cellular and molecular therapeutics, these studies may also lead to improved understanding of the plasticity and function of the nervous system and be relevant to other human neurodegenerative or traumatic conditions.