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）：此修订申请响应于NOT-OD-09-058“ NIH宣布为具有竞争性修订应用程序的恢复ACT资金的可用性”，并专注于研究杏仁核中间核的发展和功能。内侧杏仁核是边缘系统脑回路的中心结构，可调节喂养，生殖和防御行为。我们最近的研究确定了表达谱系DBX1+祖细胞池的独特发育机制，专门用于产生内侧杏仁核神经元细胞多样性。扩展这些发现，在此项目中，我们将研究中间杏仁核发展和功能的两个不同方面。首先，我们将研究DBX1在内侧杏仁核抑制性输出神经元和电路规范中的功能。这将通过条件诱变方法来实现。其次，使用先前生成的敲蛋白小鼠，其中dbx1衍生的细胞是永久标记的，我们将全面检查内侧杏仁核抑制性输出神经元的功能突触和电连通性。因此，这些研究将提供大脑发育与大脑功能之间的联系。 公共卫生相关性：哺乳动物杏仁核是大脑边缘系统的核心结构，它是一种脑电路，可与情感和动机显着性协调对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，例如自闭症谱系障碍。该建议是针对理解内侧杏仁核的发展和功能之间联系的，因此将提供对杏仁核功能改变的人类疾病的宝贵见解。