Specificity and Development of Dopaminergic Intracerebral Grafts

Finger, Thomas

Abstract

Transplantation of developing neurons or of cell lines is one approach to treating disorders such as Parkinson's disease which involve loss of specific neurons from the CNS. Experiments in this section are designed to examine the specificity and development of such transplanted neurons or cell lines. Previous studies have established that processes from grafted neurons-both dendrites and axons-extend into the host brain. The first series of experiments will test whether graft-host interconnections are specific. Combined retrograde labeling and immunocytochemical means will be used to determine whether graft-derived neuritic extensions originate only from dopaminergic neurons, or whether neurons of other types also project into the host brain. In addition, ultrastructural immunocytochemical methods will be employed in order to determine whether host inputs to dopaminergic, graft-derived dendrites is appropriate or not. The second series of experiments will test whether grafted neurons follow a normal course of biochemical development and whether the immediate host environment influences this time course. These experiments will utilize in an attempt to find a source of transplantable cells that will differentiate into dopaminergic neurons. The morphology, function and connectivity of these cells will be assessed with behavioral, electrophysiological, electrochemical and morphological means.