The long term objective of this project is to obtain a better understanding of the regulation of cholinergic innervation of the cerebral cortex. Since most of the cholinergic input to the neocortex arises from the Nucleus Basalis of Meynert, the proposed studies in this project ar focused on the elucidation of the anatomical and physiological properties of neurons in the rat substantia innominata - ventral pallidum (SI-VP) complex, within which are located the cortex-projecting neurons homologous to the cholinergic neurons of the primate Nucleus Basalis of Meynert. The planned studies will use the technique of intracellular recording In Vivo to analyze physiological properties of neurons in the rat SI-VP complex. The nature of afferent inputs will be studied by stimulation of respective areas. Moreover, we will utilize the technique of intracellular labeling with biocytin to examine the morphology and the synaptic relationships of the physiologically identified neurons. Since most neurons within the SI-VP complex are not cholinergic neurons, we will employ double-labeling methods to identify the transmitter contained within the intracellularly labeled neurons, and to determine their synaptic relationships with other immunocytochemically identified neuronal elements. We will carry out other additional single and double-labeling immunocytochemical studies at both light microscopic and electron microscopic levels in order to determine the distribution and the synaptic relationships of various non-cholinergic neurons in rat SI-VP complex. These information will be useful in the revising our current functional model of the Nucleus Basalis of Meynert, and may contribute to formulation of both preventive and therapeutic treatments of Alzheimer's Disease.
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