This proposal will explore the detailed anatomy of the basal forebrain, with particular focus on the ventral striatopallidal system and the """"""""extended amygdala"""""""" and their potential output channels through the diencephalon and brainstem including their relation to corticopetal neurons in mediobasal telencephalon. Specific attempts will be made to explore cellular interactions in the sublenticular area and the lateral hypothalamus. In order to achieve this goal, two-neuron pathways originating in various compartments of the ventral striatopallidal system and extended amygdala will be examined both on the light- and the electron microscopic levels using a combination of axonal transport methods and intracellular labelling techniques. In particular, lateral hypothalamic or sublenticular neurons that have been identified by retrograde labelling following injections of the tracer in their area of termination, will be injected with Lucifer Yellow or a comparable substance to visualize their dendritic branches and their relation to incoming afferent pathways labeled with anterograde tracer techniques. When appropriate, immunohistochemical techniques or in-situ hybridization will be used to identify the transmitters of the interacting neuronal elements. The exploration of the basal forebrain will also be carried to the human brain with the particular goal of identifying by means of histochemical methods or in-situ hybridization, presynaptic transmitters to morphologically characterized neurons, particularly in the ventral striatopallidum, extended amygdala, and the basal nucleus of Meynert. The basal forebrain systems to be explored in this study are involved to a significant degree in a number of crippling brain disorders including Alzheimer's disease. Parkinson's disease, and schizophrenia, and the anatomical studies proposed in this application will provide the details necessary to provide a conceptual framework for physiologic, behavioral and clinical studies of forebrain functions relevant to these disorders.
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