Development of the basal telencephalic limbic system

基础端脑边缘系统的发育

• 批准号: 7821751
• 负责人: JOSHUA G CORBIN
• 金额: $ 34.78万
• 依托单位: CHILDREN'S RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2012-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7821751
• 关键词: Accessory Olfactory Bulbs; Addictive Behavior; Amygdaloid structure; Behavior; Behavioral; Brain; Brain Diseases; Cell Nucleus; Cells; Cellularity; Chemicals; Coupled; Cues; Data; Defect; Development; Disease; Effectiveness; Electrical Synapse; Embryo; Embryonic Development; Emotional; Event; Frequencies; Functional disorder; Funding; Gap Junctions; Generations; Genes; Goals; Human; Hypothalamic structure; Knock-out; Knockout Mice; Laboratories; Limbic System; Link; Longitudinal Studies; Measures; Medial; Mediating; Mus; Mutagenesis; Neurons; Output; Parents; Play; Population; Preoptic Areas; Preparation; Process; Recovery; Regulation; Reporter; Role; Stimulus; Structure; Synapses; Testing; United States National Institutes of Health; Work; addiction; autism spectrum disorder; biocytin; clinically relevant; connexin 36; developmental disease; feeding; gap junction channel; homeodomain; inhibitory neuron; insight; interdisciplinary approach; nerve stem cell; neurogenesis; olfactory bulb; progenitor; public health relevance; reproductive; response; reward circuitry; voltage clamp

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.

描述（由申请人提供）：本修订申请是对NOT-OD-09-058“NIH宣布恢复法案资金可用于竞争性修订申请”的回应，重点是杏仁核内侧核的发育和功能研究。内侧杏仁核是边缘系统大脑回路的中心结构，调节进食、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，其中同源结构域表达Dbx 1+祖细胞池专门用于产生内侧杏仁核神经元细胞的多样性。扩展这些发现，在这个项目中，我们将研究两个不同的方面内侧杏仁核的发展和功能。首先，我们将研究Dbx 1在内侧杏仁核抑制性输出神经元和回路的特化中的功能。这将通过条件诱变方法完成。其次，使用先前产生的敲入小鼠Dbx 1衍生的细胞被永久标记，我们将全面研究内侧杏仁核抑制性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。 公共卫生关系：哺乳动物杏仁核是大脑边缘系统的中心结构，边缘系统是一种大脑回路，可以协调对具有情感和动机显着性的刺激的适当行为反应。杏仁核功能障碍与许多脑部疾病有关，包括成瘾行为和发育障碍，如自闭症谱系障碍。这一建议是针对了解内侧杏仁核的发育和功能之间的联系，从而将提供有价值的洞察杏仁核功能改变的人类疾病。