One of the most overlooked aspects of Neuroscience is gender and its impacts on the brain. Historically, gender specificity has been ignored in order to avoid experimental variability. However, it is becoming clear in recent years that biological impacts of gender profoundly alters the way the brain responds to its environment. Therefore, the long range goal of this project is to understand how gender alters the brain?s response to estradiol. This goal is important because it challenges some of the current assumptions about how the brain responds to hormones. There is an extensive literature that documents the beneficial effects of estrogen on the brain. It is also known that both female and male brains are exposed to estradiol, from the ovaries and/or via the conversion of testosterone to estrogen by the enzyme aromatase. However, less is known about how gender alters the brain?s response to estrogen. To address this issue, male and female rat neurons are cultured separately and used as an experimental model system to examine biochemical responses to estradiol. Based on preliminary data, it is predicted that male neurons are less responsive to estradiol than female neurons. The current project will confirm or reject this prediction and future work will determine whether this gender difference is genetic or a consequence of in utero hormone exposure. This project is consistent with the goals of the National Science Foundation: ?To promote the progress of science; advance the national health, prosperity and welfare?? Given that gender differences are central to understanding the human condition, a better understanding of its role will serve to advance national health, prosperity and welfare. The project will offer unique training opportunities for undergraduate students who will work on this project.