Estrogen Modulation of Learning Strategy: A Neural Systems Approach

这个项目的目标是确定雌激素作用于调节学习和记忆的大脑区域。基本的假设是，雌激素对学习和记忆的影响特定于学习类型和相关的大脑区域，用于解决不同的迷宫。利用两种不同类型的学习策略--位置学习和反应学习--的两个迷宫，将被用来确定雌激素是否分别直接作用于特定的离散大脑部位，即海马体和背侧纹状体，这些部位对这些任务的良好表现至关重要。两个实验检测了雌激素在切除卵巢的大鼠学习中的作用，从而消除了雌激素的内在来源。在第一个实验中，大鼠将雌激素直接注入海马体或纹状体，然后进行定位和反应学习测试。在第二个实验中，在将雌激素阻滞剂直接注射到海马体或纹状体后，大鼠将接受血液循环中的雌激素注射，然后对大鼠进行定位和反应学习测试。先前的一些报告表明雌激素会损害学习和记忆，而另一些报告则表明雌激素可以改善学习和记忆。本提案所采取的办法表明这两个结论都是正确的，从而澄清了这些相互矛盾的报告的依据。雌激素可能会激活或抑制不同的大脑区域，从而改变所使用的学习策略，从而改变在不同的激素条件下学习什么，而不一定是学习多少。雌激素对学习策略的影响是由不同的神经系统控制的，这一基本发现将有助于理解随着更年期激素下降而出现的神经和认知过程。

The goal of this project is to identify the brain areas through which estrogen acts to modulate learning and memory. The underlying hypothesis is that the effects of estrogen on learning and memory are specific to types of learning, and associated brain areas, used to solve different mazes. Two mazes that tap two different types of learning strategies, place learning and response learning, will be used to determine whether estrogen acts directly at specific discrete brain sites, the hippocampus and dorsal striatum, respectively, important for good performance in these tasks. Two experiments examine the role of estrogen on learning in rats that have had their ovaries removed, thus removing the intrinsic source of estrogen. In the first experiment, rats will receive estrogen directly into either the hippocampus or the striatum and will then be tested for place and response learning. In the second experiment, rats will receive injections of estrogen into the circulation after an estrogen blocker is administered directly into the hippocampus or the striatum, and the rats will then be tested for place and response learning. Some prior reports suggest that estrogen impairs learning and memory, while other reports indicate that estrogen improves learning and memory. The approach taken in this proposal may clarify the basis for these conflicting reports by showing that both conclusions are correct. Estrogen might activate or inhibit different brain areas, thereby changing the learning strategy used and thus what and not necessarily how much is learned under different hormone conditions. The basic finding that estrogen's effects on learning strategy are governed by different neural systems will prove useful for understanding the neural and cognitive processes that accompany the decline in hormones with menopause.