As interest in the potential clinical applications of neural transplantation technology continues to grow, it becomes increasingly important to understand fundamental principles of neural development which regulate the anatomical and functional relationships established between neural grafts and the brains of neurologically imparied transplant recipients. The present proposal continues a line of experimentation designed to analyze the conditions of transplantation which favor the survival, differentiation and structural and functional integaration of hypothalamic peptidergic neurons grafted into the host brain. In these experiments the peptide hormone vasopressin is used as a marker to identify neuronal populations of interest within the transplants (specifically, anlagen of the suprachiasmatic nuclei, magnocellular neurosecretory system and parvicellular components of the paracentiricular nuclei). Other selected peptidergic and monoaminergic markers (and tract tracing techniques) are utilized to assess the degree to which, under varying conditions of transplantation, these populations of vasopressinergic neurons have retained specific connectional and neuronchemical attributes which ordinarily distinguish these neuronal populations one from another in situ. In one series of experiments, neurons will be dissected from specific subregions of the developing hypothalamus, and grafted into the periventiricular hypothalamus of vasopressin-deficient Brattleboro rats. The purpose of this study is to determine the effects of age and the specific locus of origin of the donor tissue on the survival, differentiation and intergration of morphologically distinct subtypes of vasopressin neurons. In a second, related experimental series, the effects of differential patterns of neuronal loss in the host hypothalamus on the development of the grafted neurons will be systematically evaluated. Throughout, this project will employ a multidisciplinary approach to investigate the structural, neurochemical and functional relations of the vasopressinergic neurons in the transplants. These experiments should enhance our understanding of the fundamental principles which regulate the establishment of appropriate anatomical and neurochemical relationships during normal brain development. This, in turn, may aid in the formulaiton of new procedures to alleviate neurological deficits that result from CNS trauma or disease.
