Estrogen, Cholinergic and Gabaergic Activity, and Memory

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Recent studies suggest that estrogen can influence cognitive processes.It is hypothesized that these effects are due, in part, to the ability ofestrogen to enhance the functional status of cholinergic projections tothe hippocampus and cortex by affecting cholinergic and GABAergicneurons within specific regions of the basal forebrain.The proposed studieson rats will use a combination of biochemical,pharmacological, and behavioral techniques to examine the effects ofestrogen replacement on basal forebrain cholinergic neurons andcorresponding cognitive processes. One major goal is to test thehypothesis that estrogen replacement can reduce cognitive impairmentsassociated with the loss of basal forebrain cholinergic neurons. Thisgoal will be accomplished by examining the ability of estrogenreplacement to reduce impairments in learning, memory and attentionalprocesses produced by selective cholinergic lesions in rats. Anothermajor goal is to examine the ability of estrogen to reduceGABA-receptor-mediated effects on cholinergic activity. This will beaccomplished using an in vivo microdialysis approach and examining theability of estrogen to prevent decreases in acetylcholine releaseproduced by lorazepam.These studies will help provide an integrated, mechanistic account ofhow estrogen replacement influences interactions between cholinergic andGABAergic systems in the basal forebrain and hippocampus, and will helpto define potential mechanisms by which estrogen replacement can reducecognitive impairments associated with alterations in cholinergic andGABAergic activity.