The overall objective is to obtain a better understanding of the regulation of the cholinergic innervation of the cerebral cortex. We propose experiments which are expected to provide answers to questions concerning the functional and anatomical organization of the cholinergic neurons in the Nucleus Basalis of Meynert and their relationships with the ventral strio-pallidal system. The planned studies will use the technique of intracellular recording IN VIVO to study the physiological properties of Nucleus Basalis neurons. The nature of afferent inputs will be studied by stimulation of respective areas. Moreover, we will utilize the technique of intracellular horseradish peroxidase labeling to examine the morphology and the synaptic relationships of the physiologically identified Nucleus Basalis neurons. We will also perform experiments involving histochemistry and/or immunocytochemistry on tissue containing intracellularly labeled neurons in order to determine the neurochemical properties of the labeled neurons and their synaptic partners. The multidisciplinary studies proposed in this project are unique to the ventral forebrain. The data will enhance our understanding of both the intrinsic functional organization of neurons in the Nucleus Basalis, and the nature of afferent regulations of cholinergic neurons which innervate the cortex. This information will be useful in the formulation of both preventive and therapeutic treatments of Alzheimer's Disease.
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