Development of the basal telencephalic limbic system

描述(由申请人提供)：本修订申请是对NOT-OD-09-058《美国国立卫生研究院宣布恢复法案资金可用于竞争性修订申请》的回应，重点研究杏仁核内侧核的发育和功能。杏仁内侧核是边缘系统大脑回路的中心结构，负责调节摄食、生殖和防御行为。我们最近的研究已经确定了独特的发育机制，在这些机制中，表达同源结构域的Dbx1+祖细胞池专门用于产生杏仁内侧神经元细胞多样性。在这些发现的基础上，在这个项目中，我们将研究杏仁内侧核发育和功能的两个不同方面。首先，我们将研究Dbx1在杏仁内侧核抑制性输出神经元和回路中的功能。这将通过有条件的突变方法来实现。其次，使用先前产生的敲击小鼠，在其中Dbx1衍生细胞被永久标记，我们将全面检查杏仁内侧核抑制输出神经元的功能突触和电连接。因此，这些研究将提供大脑发育和大脑功能之间的联系。 与公共健康相关：哺乳动物的杏仁核是大脑边缘系统的中心结构，大脑边缘系统是一个大脑回路，协调对刺激的适当行为反应，具有情绪和动机的突出。杏仁核功能障碍与许多大脑疾病有关，包括成瘾行为和发育障碍，如自闭症谱系障碍。这一建议旨在了解杏仁内侧核发育和功能之间的联系，从而为人类杏仁核功能改变的疾病提供有价值的见解。

DESCRIPTION (provided by applicant): This revision application is in response to NOT-OD-09-058 "NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications" and is focused on the study of the development and function of the medial nucleus of the amygdala. The medial amygdala nucleus is a central structure of limbic system brain circuitry that regulates feeding, reproductive and defensive behaviors. Our recent studies have identified unique developmental mechanisms in which homeodomain-expressing Dbx1+ progenitor pools are dedicated for the generation of medial amygdala neuronal cell diversity. Expanding on these findings, in this project we will examine two distinct aspects of medial amygdala development and function. First, we will study the function of Dbx1 in the specification of medial amygdala inhibitory output neurons and circuitry. This will be accomplished by conditional mutagenesis approaches. Second, using previously generated knockin mice in which Dbx1-derived cells are permanently marked, we will comprehensively examine the functional synaptic and electrical connectivity of medial amygdala inhibitory output neurons. Thus, these studies will provide a link between brain development and brain function. PUBLIC HEALTH RELEVANCE: The mammalian amygdala is a central structure of the brain's limbic system, a brain circuit that coordinates appropriate behavioral responses to stimuli with emotional and motivational salience. Amygdala dysfunction is associated with numerous brain disorders including addictive behavior and developmental disorders such as autism spectrum disorders. This proposal is directed toward understanding the link between development and function of the medial amygdala nucleus, and thus will provide valuable insight into human disorders in which amygdala function is altered.