Estrogen, L:earning Strategy, and Neural Systems: Timing and Cell Mechanisms

雌激素对认知和相关的大脑区域有显著的影响。 PI已经表明，在大鼠中，雌激素提高了需要定位或“去那里”策略的导航任务的性能，并损害了使用响应或“转向这边”策略的任务的性能。 重要的是，位置和反应策略的使用映射到参与认知的特定神经系统，即海马和背侧纹状体。 PI实验室以前的工作表明，雌激素直接作用于海马和纹状体，分别增强位置学习和损害反应学习。 该项目的目标是确定雌激素对大鼠学习的相反作用的机制。 这些实验测试了雌激素对海马和纹状体的认知作用是否1）通过雌激素的缓慢和快速作用来区分，2）通过不同的雌激素受体起作用，这些受体是结合雌激素并调节其细胞和基因作用的分子，3）由CREB介导，CREB是一种重要的记忆分子，被雌激素激活。 这些研究的结果将促进我们对生殖激素对大脑功能和记忆系统影响的认识。 这些活动还将对许多层次和不同群体的科学教育产生直接影响。 PI指导许多研究生，包括来自代表性不足的群体的研究生，具有将本科生和高中生纳入研究的悠久历史，其中6人共同撰写了最近的出版物，并为学童开发和实施动手科学课程。

Estrogen has dramatic effects on cognition and associated brain regions. The PI has shown that, in rats, estrogen improves performance on navigational tasks requiring place or "go there" strategies and impairs performance on tasks using response or "turn this way" strategies. Importantly, the use of place and response strategies maps onto specific neural systems involved in cognition, namely the hippocampus and the dorsal striatum, respectively. Previous work in the PI's laboratory demonstrates that estrogen acts directly at the hippocampus and striatum to enhance place learning and impair response learning, respectively. The goals of the project are to determine the mechanisms underlying the opposing effects of estrogen on learning in rats. The experiments test whether the cognitive effects of estrogen at the hippocampus and striatum 1) are differentiated by slow and rapid actions of estrogen, 2) act through different estrogen receptors, molecules that bind estrogen and regulate its cellular and gene actions and 3) are mediated by CREB, an important memory molecule shown to be activated by estrogen. Results from these studies will advance our knowledge about reproductive hormone effects on brain function and memory systems. These activities will also have a direct impact on scientific education at many levels and in diverse groups of individuals. The PI mentors many graduate students including those from underrepresented groups, has a long history of incorporating undergraduate and high-school students in research, 6 of whom co-authored recent publications, and develops and implements hands-on science curricula for school children.