Estrogen Receptor Beta in the Developing Prefrontal Cortex

类固醇雌激素调节大脑的许多功能，包括行为和认知，而前额叶皮质(PFC)是控制认知功能和情绪行为的大脑区域。不足为奇的是，PFC对雌激素敏感，但目前人们对它对雌激素的反应知之甚少。因此，这项研究的目标是确定雌激素如何调节PFC。这项研究测试了两种主要类型的雌激素受体，即阿尔法和贝塔，即PFC受贝塔(ERb)调节的预测。这些研究的成功完成将为PFC中一种重要但尚未探索的神经元表型提供新的信息。创新的方法被用来检查ERb神经元，这些研究的结果可以影响到多个研究领域。该研究项目将用于培训高中生、本科生和研究生，特别是在神经科学方面代表性不足的少数族裔。结果将通过同行评议的出版物以及学生在地方和国家会议上的陈述来传播。这些研究探索了小鼠PFC中表达Erb的一组选定细胞的功能。PFC控制许多行为，包括认知、注意力和神经内分泌应激反应。雌激素可以改变这一脑区的发育，然而，对PFC中表达Erb的神经元知之甚少，部分原因是缺乏有效的试剂来检测大脑中的Erb。这项拟议的研究将使用一种在ERb神经元中表达荧光蛋白的新型转基因小鼠来检查PFC中的这组神经元。初步结果表明，在PFC发育过程中，表达ERb的神经元的位置发生了变化。这项应用中的研究将解决这样的假设，即这些变化反映了不同皮质层中雌激素敏感性随时间的发育变化。利用解剖学方法，这些研究将确定表达ERb的皮质神经元的身份。接下来，我们将用分子方法来解释雌激素受体水平在大脑皮质发育过程中数量和位置变化的原因，最后，我们将用电生理学的方法来研究已识别的erb神经元在前额叶皮质中的功能。

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