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

雌激素对认知和相关大脑区域有显著影响。PI已经表明，在大鼠中，雌激素提高了需要地点或“去那里”策略的导航任务的表现，并削弱了使用反应或“转向”策略的任务的表现。重要的是，位置和反应策略的使用分别映射到与认知相关的特定神经系统，即海马和背纹状体。PI实验室先前的研究表明，雌激素直接作用于海马体和纹状体，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。本实验检验了雌激素在海马和纹状体的认知作用是否1)通过雌激素的慢速和快速作用来区分，2)通过不同的雌激素受体、结合雌激素并调节其细胞和基因作用的分子起作用，3)由雌激素激活的重要记忆分子CREB介导。这些研究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个人群体的科学教育产生直接影响。PI指导了许多研究生，包括那些来自代表性不足群体的学生，在让本科生和高中生参与研究方面有着悠久的历史，其中6人是最近出版物的合著者，并为在校儿童开发和实施了动手科学课程。

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.