The long-term objective of this project is to understand the relation among recent memory, septohippocampal function, and aging. Normal aging and age-related neurodegenerative diseases can both produce impairments of memory. Understanding the neural mechanisms related to these memory impairments, and attempting to alleviate them through neural manipulations, can have a significant impact on the quality of life of the aged population. This project has three specific goals. (1) Determine the extent to which direct microinfusion of substances into the medial septal area (MSA) of rats can improve mnemonic function in aged rats with impaired memory, and examine the correlations among mnemonic improvements, hippocampal electrophysiology as measured by theta, and cholinergic stimulation as measured by hemicholinium-3 (HC-3) binding. (2) Determine the extent to which aging changes the sensitivity of the septohippocampal system to disruption by compounds directly infused into the MSA, producing shifts of the dose-response curve relating the dose of these compounds to the magnitude of the memory impairment. (3) Examine the individual differences in aged populations with respect to the magnitude of the memory impairment, sensitivity to MSA infusions, and activity of the cholinergic system as examined by HC-3 binding. The experimental design tests rats of 4 different ages in two tasks to assess recent memory. Compounds infused into the MSA are designed to stimulate and inhibit, respectively the cholinergic system (scopolamine, oxotremorine) and the GABAergic system (picrotoxin, bicuculline, muscimol). Theta is recorded from the hippocampus to indicate the electrophysiological effects of these compounds. HC-3 is measured to determine the extent to which cholinergic system is affected.
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