The specific aims of this proposal are (a) to determine the morphologies, projection patterns, degree of collateralization, acetylcholinesterase staining characteristics, and relationship to the total population of somata demonstrated by Nissl stains of the choline-O-acetyltransferase positive projection cells in the basal forebrain and brainstem and (b) to ascertain the morphologies, staining features, and possible projection patterns of neurons in the rat caudate-putamen complex proper demonstrating somatostatin-like immunoreactivity and to compare those cells, on the same tissue section, with striatal neurons containing acetylcholinesterase and those staining for Nissl substance. Methodologies used to achieve these aims include microscopic evaluation of retrograde and anterograde transport of fluorescent labels and lesion-induced retrograde and anterograde degeneration; immunohistochemistry for choline-O-acetyltransferase and somatostatin; histochemical methods for acetylcholinesterase, including the pharmacohisto-chemical protocol; and traditional histologic procedures. Correlative biochemical experiments will also be performed. The long-term objective of this research is two-fold: (a) to further our understanding of the morphologies, distribution, and projection patterns of cholinergic neurons (i.e., those that synthesize and use acetylcholine to communicate with other tissue entities) in the central nervous system and (b) to assess possible relationships among those neurons and other neurochemically and histochemically identifiable neuronal systems in the brain and spinal cord. The underlying raison d'etre of this approach is to gain insights from analyses of the chemical communication matrix of the nervous system as to how chemically identifiable neuronal systems operate, both singly and in combination, to influence behavior, and various physiologic processes, both normal and pathologic. This research should have relevance not only for understanding the neurochemical organization of the basal ganglia, basal forebrain, and histochemically related regions, but also for human disorders involving those structures, including Alzheimer's disease, Parkinsonism, and Huntington's chorea.
