Estrogen Receptor Beta in the Developing Prefrontal Cortex

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The steroid estrogen regulates many functions of the brain including behavior and cognition, while the prefrontal cortex (PFC) is a brain region that controls aspects of cognitive function and emotional behavior. Not surprisingly the PFC is estrogen sensitive, but there is currently little known about how it responds to estrogen. The goal of this research is therefore to determine how estrogen regulates the PFC. The research tests the prediction that of the two main types of estrogen receptors, alpha and beta, that the PFC is regulated by beta (ERb). Successful completion of these studies will provide novel information about an important but unexplored neuronal phenotype in the PFC. Innovative approaches are used to examine ERb neurons and the results of these studies can impact multiple research arenas. This research project will be used for the training of high school, undergraduate and graduate students, particularly underrepresented minorities, in neuroscience. Results will be disseminated through peer-reviewed publication and by student presentations at local and national meetings. These studies explore the function of a select group of cells in the mouse PFC that express ERb. The PFC controls many behaviors including cognition, attention, and neuroendocrine stress responses. Estrogen can alter the development of this brain region, yet, little is known of the neurons in the PFC that express ERb, partly due to the absence validated reagents allowing the detection of ERb in brain. The proposed studies will examine this group of neurons in the PFC using a novel transgenic mouse that express a fluorescent protein in ERb neurons. Preliminary results show that the location of ERb expressing neurons changes across development of the PFC. Studies in this application will address the hypothesis that these changes reflect developmental alterations in estrogen sensitivity in different cortical layers across time. Using anatomical approaches, these studies will determine the identity of the cortical neurons that express ERb. Next, molecular approaches will be used to address the reason why estrogen receptor levels change in amount and location during cortical development and lastly, the function of identified ERb neurons in the PFC will be examined using electrophysiology