Hormones and Learning and Memory

任何经历过青春期、怀孕、更年期或男性更年期的人都可以证明，荷尔蒙对我们的大脑和身体产生了强大的影响。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。关于使用雌激素来促进老年女性的认知，有很多争议，可能是因为文献中相互矛盾的报告。我们最近发现，雌二醇对学习的影响是不同的，这取决于任务的类型(甚至是执行任务所需的大脑区域)和雌性啮齿动物服用雌二醇的剂量。高水平的雌二醇会损害工作记忆(随着试验的不同而变化的记忆，即你每天把车停在哪里)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)，而低水平的雌二醇会通过前额叶皮质和海马体促进工作记忆。这些发现表明，雌二醇对参与工作记忆的不同大脑区域(前额叶皮质和海马体)的学习具有积极的剂量依赖效应，但可能对涉及参考记忆(海马体、尾状核)和条件性学习(杏仁核)的大脑区域产生不利影响。在这项提案中，我计划研究雌二醇如何影响学习和记忆；特别是，雌二醇通过哪些大脑区域和机制对学习和记忆产生影响。我计划用药理学和组织学的方法来研究这些假说：包括将雌激素注入不同的大脑区域，以确定雌激素在哪些部位发挥作用；确定雌激素对不同类型的学习和记忆的影响可能涉及哪种特定类型的雌激素受体；以及雌激素与其受体和基因表达相互作用以发挥其对认知的影响的机制。了解雌激素等激素如何影响认知，可能会更好地理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.