Estrogen, Cholinergic and Gabaergic Activity, and Memory

最近的研究表明，雌激素可以影响认知过程。部分原因是雌激素通过影响基底前脑特定区域的胆碱能和GABA能神经元，提高了向海马区和皮质的胆碱能投射的功能状态。拟在大鼠身上进行的研究将结合生化、药理学和行为技术来检测雌激素替代对基底前脑胆碱能神经元和相应认知过程的影响。一个主要的目标是检验雌激素替代可以减少与基底前脑胆碱能神经元丧失相关的认知损害的假设。这一目标将通过检测雌激素替代减少选择性胆碱能损伤所产生的学习、记忆和注意力过程的损害的能力来实现。另一个主要目标是检查雌激素减少GABA受体介导的胆碱能活动的能力。这将通过体内微透析方法和检测雌激素防止劳拉西潘产生的乙酰胆碱释放减少的能力来完成。这些研究将有助于提供一个综合的机制，说明雌激素替代如何影响基底前脑和海马区胆碱能和GABA能系统之间的相互作用，并将有助于确定雌激素替代可以减少与胆碱能和GABA能活性改变相关的认知损害的潜在机制。

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.