Hormones and Learning and Memory

任何一个经历过青春期、怀孕、更年期或男性更年期的人都可以证明，激素对我们的大脑和身体有着强大的影响。雌激素，特别是丰富的“年轻”雌激素，雌二醇，可以对大脑和行为产生深远的影响。关于使用雌激素促进老年妇女认知能力的争议很多，可能是由于文献中相互矛盾的报道。我们最近发现，雌二醇对学习的影响不同，这取决于任务的类型（实际上是执行任务所需的大脑区域）和雌性啮齿动物服用的雌二醇剂量。高水平的雌二醇会损害工作记忆（从一次试验到另一次试验的记忆，即你每天停车的地方）和参考记忆（随着时间的推移保持稳定的记忆，即停车场在哪里），而低水平的雌二醇通过前额皮质和海马促进工作记忆。这些发现表明，雌二醇对参与工作记忆的不同脑区（前额叶皮层和海马）的学习有积极的剂量依赖性影响，但可能对参与参考记忆（海马，尾状核）和条件学习（杏仁核）的脑区有不利影响。在这个建议中，我计划研究雌二醇如何影响学习和记忆;特别是，哪些大脑区域，以及通过哪些机制，雌二醇发挥其对学习和记忆的影响。我计划用药理学和组织学方法来研究这些假说：包括将雌二醇注入不同的脑区，以确定雌激素在哪些部位发挥作用;确定哪种特定类型的雌激素受体可能参与雌二醇对不同类型的学习和记忆的影响;以及雌二醇通过与受体和基因表达相互作用而发挥其认知功能的机制。了解雌二醇等激素如何影响认知，可能会更好地了解学习和记忆在大脑中是如何组织的。

As anyone who has gone through puberty, pregnancy, menopause or andropause can attest, hormones exert powerful effects over our brains and body. Estrogens, particularly the abundant "youthful" estrogen, estradiol, can exert profound effects on both brain and behaviour. There is a lot of controversy surrounding the use of estrogens to promote cognition in older women, likely due to conflicting reports in the literature. We have recently found that estradiol affects learning differentially depending on the type of task (and indeed the brain region required to perform the task) and the dose of estradiol administered to female rodents. High levels of estradiol impair both working (memory that changes from trial to trial, i.e. where you park your car every day) and reference memory (memory that stay stable over time, i.e where the parking lot is), while low levels of estradiol facilitate working memory via the prefrontal cortex and hippocampus. These findings suggest that estradiol has a positive dose-dependent effect on learning in different brain regions that are involved in working memory (prefrontal cortex and hippocampus) but may have a detrimental effect on brain regions that are involved in reference memory (hippocampus, caudate) and conditioned learning (amygdala). In this proposal I plan to study how estradiol affects learning and memory; in particular, which brain regions, and by which mechanisms, does estradiol exert its effects on learning and memory. I plan to investigate these hypotheses using pharmacological and histological methods: including infusions of estradiol into different brain areas to determine at which sites estrogen exerts its actions; determining which particular type of estrogen receptor that might be involved in estradiol's effects on different types of learning and memory; and the mechanism by which estradiol interacts with it's receptors and gene expression to exert its' effects on cognition. Understanding how hormones such as estradiol can influence cognition, may lead to a better understanding of how learning and memory is organized in the brain.