Development of the basal telencephalic limbic system

描述（由申请人提供）：此修订申请是对NOT-OD-09-058“NIH宣布为竞争性修订申请提供恢复法案基金”的回应，重点是研究杏仁核内侧核的发育和功能。内侧杏仁核是大脑边缘系统回路的中心结构，负责调节进食、繁殖和防御行为。我们最近的研究已经确定了独特的发育机制，其中同源结构域表达Dbx1+祖细胞池专门用于内侧杏仁核神经元细胞多样性的产生。在这些发现的基础上，在这个项目中，我们将研究内侧杏仁核发育和功能的两个不同方面。首先，我们将研究Dbx1在内侧杏仁核抑制输出神经元和电路中的功能。这将通过条件诱变方法来实现。其次，使用先前生成的敲入小鼠，其中dbx1来源的细胞被永久标记，我们将全面检查内侧杏仁核抑制输出神经元的功能性突触和电连接。因此，这些研究将提供大脑发育和大脑功能之间的联系。

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.