As a result of the very rapid recent progress of the neural implantation work, the emphasis of our project has during the current grant period shifted. Thus, during the forthcoming grant period we want to focus the work on: (1) Further studies on the detailed organization of the central dopaminergic projection systems, with special emphasis on the recently discovered dopamine innervations of the hypothalamic neurosecretory nuclei, the lower brainstem and the spinal cord. (2) Further studies on transmitter mechanisms in intracerebral grafts of neuronal cell suspensions. The studies on neuronal grafts are proposed to proceed along four different lines: (a) Exploration of the possibilities to use cultured mesencephalic and septal neurons for neural grafting in adult rats with lesions of the intrinsic dopaminergic or cholinergic systems. (b) Studies on the ability of implants of dopamine-rich mesencephalic cell suspensions to reinnervate limbic and/or cortical forebrain sites and to compensate for the functional deficits induced by 6-hydroxydopamine lesions of the meso-limbo-cortical dopamine pathway. (c) Studies on the ability of implants of suspended brainstem noradrenergic or serotoninergic neurons to reinnervate the hippocampus and spinal cord in rats with lesions of the intrinsic noradrenergic or serotoninergic systems. (d) Further morphological and functional studies on neuronal replacement in the ibotenic acid-lesioned striatum in adult rats. These studies should further promote our understanding of mechanisms of regeneration and functional recovery under experimental conditions which mimic the neurotransmitter pathology in some neurodegenerative disease states in man. The neuroanatomical studies, moreover, should contribute to a better understanding of the role of hypothalamic, brain stem and spinal dopamine projections in the dopaminergic control of sensory and autonomic functions.
