Grant: Discovery Grants Program - Individual

As anyone who has gone through adolescence, pregnancy, or aging can attest: hormones can exert powerful effects on brain and behaviour. My NSERC-related research has focussed on how hormones and biological sex can affect the brain to influence learning and memory. Why study sex differences in memory? Men and women differ in their susceptibility to develop memory problems, and show different brain responses to memory. For example, men are more likely to have memory problems with schizophrenia whereas women are more likely to have memory problems with depression or more severe memory loss with Alzheimer's disease. Hence, to gain a better understanding of how memories are formed in both sexes, it is important to acknowledge and study differences that might arise between both sexes in response to memory. Furthermore, estrogens, particularly estradiol, can exert profound effects on memory. There is a lot of controversy surrounding the use of estrogens to promote cognition in women, likely due to conflicting reports in the literature. We have found that estradiol, the most powerful of the estrogens, affects learning and memory differentially depending on the memory task and the amount estradiol given. 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). However, low levels of estradiol facilitate working memory. These findings suggest that estradiol has different effects on learning dependent on the dose given with positive effects on working memory but detrimental effects on reference memory. The hippocampus, an important brain area for memory, produces new brain cells throughout the lifespan in rodents and humans and these new cells play a crucial role in different forms of memory. We found that males and females differ in the hippocampus's response to memory, as well as we see differences in the production of new cells in response when females have different levels of estrogens. These findings suggest that there are different pathways that are involved in learning and memory between the sexes and/or with different levels of estradiol. In this proposal, we plan to study how both factors (sex and estradiol) affect where and how learning and memory occurs in the brain. We will examine 1) activation of the hippocampus and other brain areas after memory, 2) how new brains cells respond to memory, and 3) whether the mechanisms in the brain cells driving memory are different in males and females, or females with different levels of estradiol. Understanding how biological sex and hormones can influence memory, may lead to a better understanding of how learning and memory is organized in the brain in both males and females, and ultimately of why some people are more susceptible to memory problems than others.