Characterization of Sexual Dimorphism in the Brain

项目总结/摘要 我们申请基金的目的是对纹床核进行功能性和解剖性的解剖 终端（BNST）。这个核心调节着许多行为，包括社交方式和互动， 对捕食者的反应，应对生理和行为压力，以及奖励反应。在BNST 是异质的，包含许多具有不同身份的神经元池。一个假设来解释 BNST的功能多样性在于不同的BNST神经元池具有不同的功能。我们以前的 工作（由以前的资助期）和其他人已经确定了一个人口的芳香化酶表达 位于BNST内侧部后内侧成分（BNSTmpm）的神经元。芳香化酶 和BNST对男性和女性的社会互动至关重要。有趣的是，我们的研究表明， 与女性相比，男性的BNSTmpm中有更多的芳香化酶+神经元。因此我们假设 芳香化酶+ BNSTmpm神经元影响两性所表现出的不同的社会互动。在 目标1，我们将使用遗传靶向工具来绘制BNSTmpm的连接性和刺激响应性 雄性和雌性的神经元。在目标2中，我们将使用遗传方法来确定必要性， BNSTmpm芳香化酶神经元在男性和女性的社会互动中的充足性。在目标3中，我们 使用我们开发的转基因小鼠来确定芳香酶在成年BNSTmpm中的作用。 神经元在调节社会互动中的作用。总之，我们提出的研究将提供深入了解 源自芳香化酶BNSTmpm神经元的神经通路及其体内功能相关性。 健康相关性：神经退行性疾病和精神疾病通常反映神经回路功能障碍 在宏观或微观水平上，这些仍然知之甚少，治疗上也很棘手。在BNST 是连接杏仁核、下丘脑和皮质网络调节社会互动的关键节点， 对各种压力的反应和奖励途径。我们提出的研究将阐明 和功能的一个子集的BNST神经元在两种性别，从而导致了一个进步的基础科学 了解这个区域和它在健康中发挥作用的神经回路，它最终可能 为未来的精神疾病治疗或诊断应用提供见解， 神经退行性疾病

Project Summary/Abstract The goal of our grant application is a functional and anatomic dissection of the mouse bed nucleus of the stria terminalis (BNST). This nucleus regulates many behaviors, including social approach and interactions, response to predators, coping with physiological and behavioral stressors, and reward responses. The BNST is heterogeneous and contains many neuronal pools with distinct identities. One hypothesis to account for the functional diversity of the BNST is that different BNST neuronal pools serve distinct functions. Our previous work (funded by prior grant periods) and that of others has identified a population of aromatase expressing neurons located in the medial division posteromedial component of the BNST (BNSTmpm). Both aromatase and the BNST are critical for social interactions in males and females. Intriguingly, our work shows that there are more aromatase+ neurons in the BNSTmpm in males compared to females. We therefore hypothesize that aromatase+ BNSTmpm neurons influence the distinct social interactions displayed by the two sexes. In Aim 1, we will use genetically targeted tools to map the connectivity and stimulus responsivity of BNSTmpm neurons in males and females. In Aim 2, we will use genetic approaches to determine the necessity and sufficiency of BNSTmpm aromatase neurons for social interactions in males and females. In Aim 3, we will use genetically modified mice we have developed to determine the role of aromatase in adult BNSTmpm neurons in the regulation of social interactions. In summary, our proposed studies will provide insight into the neural pathways emanating from aromatase BNSTmpm neurons and their functional relevance in vivo. Health Relatedness: Neurodegenerative and psychiatric conditions often reflect dysfunction of neural circuitry at a gross or microscopic level, and these remain poorly understood and therapeutically intractable. The BNST is a critical node linking amygdalar, hypothalamic, and cortical networks in the regulation of social interactions, response to various stressors, and reward pathways. Our proposed studies will shed light on the connectivity and functions of a subset of BNST neurons in the two sexes, thereby leading to an advance in basic scientific understanding of this region and the neural circuits within which it functions in health, and it may ultimately provide insights into future therapeutic or diagnostic applications for mental illness and common neurodegenerative conditions.