Hormones and Learning and Memory

点击翻译按钮获取中文摘要

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.