Functional development of motor networks

运动网络的功能开发

• 批准号: 8034345
• 负责人: David McLean
• 金额: $ 30.72万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2014-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8034345
• 关键词: Affect; Age; Anatomy; Automobile Driving; Axon; Behavior; Biological Models; Cells; Code; Complex; Confocal Microscopy; Development; Disease; Dyes; Embryo; Erinaceidae; Fishes; Fluorescent Dyes; Heterogeneity; Image; Individual; Interneurons; Label; Life; Link; Location; Mammals; Measures; Modeling; Monitor; Morphology; Motor; Motor Neurons; Movement; Mus; Nerve; Neurons; Parkinson Disease; Pattern; Periodicity; Physiological; Physiology; Play; Population; Property; Proteins; Rana; Role; Shapes; Speed; Spinal; Spinal Cord; Spinal Injuries; Structure; Swimming; Techniques; Testing; Time; Transgenic Organisms; Vertebrates; Work; Zebrafish; extracellular; in vivo; neural circuit; neuronal circuitry; progenitor; programs; public health relevance; research study; response; smoothened signaling pathway; transcription factor

DESCRIPTION (provided by applicant): Networks of rhythmically active neurons in the spinal cord are responsible for producing locomotor movements. In developing vertebrates, ventral spinal cord can be sub-divided into five zones, four of which are responsible for producing the interneurons that drive rhythmic motoneuron activity (V0-V3). Critically, interneurons that emerge from these zones are labeled by the same transcription factors and have similar morphologies and functions in different vertebrates. This has made it even easier to compare features of circuit organization in simpler model systems, like fishes and frogs, to more complex ones, like chicks and mice. What is unclear, however, is how only four progenitor zones can yield the diverse array of functionally distinct interneurons that are known to exist. Our plan is to explore the contribution of development to the functional elaboration of spinal circuitry, by studying a genetically identified population of spinal interneurons in zebrafish. Our work suggests that interneurons labeled by the transcription factor alx in zebrafish are not functionally identical and contribute to different speeds of movement. However, it is not clear how differences in the morphology, connectivity and the excitability of alx interneurons may be related to their function and whether developmental programs shape these features. The remarkable conservation of developmental mechanisms leads us to think that the patterns we find will be present broadly among vertebrates, including mammals. By doing so, we hope to better explain and treat disorders that affect the speed and coordination of movements, like Parkinson's disease or spinal injury. PUBLIC HEALTH RELEVANCE: Networks of neurons in the spinal cord generate movements, but we understand very little about their organization. We will investigate the contribution of development to the functional diversification of spinal networks using zebrafish as a model.

描述（由申请人提供）：脊髓中节律性活动神经元的网络负责产生自发运动。在发育中的脊椎动物中，腹侧脊髓可分为五个区，其中四个区负责产生驱动节律性运动神经元活动的中间神经元（V0-V3）。重要的是，从这些区域出现的中间神经元被相同的转录因子标记，并且在不同的脊椎动物中具有相似的形态和功能。这使得比较简单的模型系统（如鱼和青蛙）与更复杂的模型系统（如小鸡和老鼠）的电路组织特征变得更加容易。然而，目前尚不清楚的是，只有四个祖细胞区如何产生已知存在的功能不同的中间神经元的多样性。我们的计划是通过研究斑马鱼脊髓中间神经元的遗传鉴定群体来探索发育对脊髓回路功能阐述的贡献。我们的工作表明，斑马鱼中由转录因子alx标记的中间神经元在功能上并不相同，并且导致不同的运动速度。然而，目前尚不清楚alx中间神经元的形态、连接和兴奋性的差异如何与它们的功能相关，以及发育程序是否塑造了这些特征。发育机制的显著保守性使我们认为，我们发现的模式将广泛存在于脊椎动物中，包括哺乳动物。通过这样做，我们希望更好地解释和治疗影响运动速度和协调的疾病，如帕金森病或脊髓损伤。 公共卫生相关性：脊髓中的神经元网络产生运动，但我们对它们的组织知之甚少。我们将以斑马鱼为模型，研究发育对脊髓网络功能多样化的贡献。