Genetic dissection of locomotion

运动的基因剖析

• 批准号: 8752141
• 负责人: RICHARD S MANN
• 金额: $ 22.25万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2016-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8752141
• 关键词: Address; Adult; Aging; Animal Model; Animals; Behavior; Biological Assay; Cells; Classification; Complement; Complex; Computer software; Control Animal; Defect; Development; Dissection; Drosophila genus; Drosophila melanogaster; Dynamin; Event; Felis catus; Gated Ion Channel; Genes; Genetic; Genetic Screening; Goals; Grant; Hand; Interneurons; Invertebrates; Investigation; Knowledge; Leeches; Life; Locomotion; Logic; Measures; Mediating; Methods; Modeling; Motor; Muscle; Neurons; Output; Phenotype; Resolution; Resources; Sensory; Snakes; Solid; Stereotyping; Stroke; System; Temperature; Time; Transcriptional Regulation; Transgenes; Walking; base; central pattern generator; combat; fly; follow-up; genetic manipulation; in vivo; interest; mutant; nervous system disorder; neural circuit; neuronal circuitry; novel; optogenetics; public health relevance; relating to nervous system; research study; tool

DESCRIPTION (provided by applicant): Locomotion in all animal species relies on precise coordination: animals must synchronize a myriad of muscle flexion and extension events in a stereotyped and rhythmic manner. At the core of motor coordination are central pattern generators (CPGs), neural circuits that have the capacity to produce rhythmic outputs from relatively simple, non-rhythmic inputs. Although there exists a large amount of functional evidence for both locomotor and non-locomotor CPGs, the cellular components of CPGs that mediate coordinated locomotion in more complex systems remain largely undefined. Further, how locomotor CPG activities are integrated with each other and modified by descending and sensory inputs is also largely unknown at the cellular level. These gaps in our knowledge may be due not only to the complexity of the neural circuitry, but also a consequence of the complexity of the behaviors under investigation. To address these challenges, the long-term goal for this project is to complement and expand upon existing efforts in other systems to characterize locomotor neural circuits using the powerful genetic tools available in the fruit fly, Drosophila melanogaster. In this proposal, a novel, high-resolution assay that quantitatively measures dozens of walking parameters in the fruit fly model will be used to screen for specific mutant phenotypes that occur as a consequence of activating and/or suppressing neural activity in subsets of neurons. Follow-up experiments are proposed to identify the neurons that are responsible for these mutant phenotypes.

描述（由申请人提供）：所有动物物种的运动都依赖于精确的协调：动物必须以刻板印象和节奏的方式同步无数的肌肉屈曲和延伸事件。运动协调的核心是中央模式发生器（CPG），神经回路具有从相对简单的非节律输入中产生节奏输出的能力。尽管存在大量的运动和非核心CPG的功能证据，但是在更复杂的系统中介导协调的运动的CPG的细胞成分仍然在很大程度上不确定。此外，在细胞水平上，运动方式相互整合并通过降序和感觉输入进行了修改，并通过降序和感觉输入进行了修改。我们知识中的这些差距不仅是由于神经回路的复杂性，而且还归因于所研究行为的复杂性的结果。为了应对这些挑战，该项目的长期目标是补充和扩展其他系统中现有的努力，以使用果蝇中可用的强大遗传工具来表征运动神经电路， 果蝇Melanogaster。在此提案中，一种新颖的高分辨率测定法，该测定法在果蝇模型中定量测量数十个步行参数将用于筛选由于激活和/或抑制神经元子集中神经活动而发生的特定突变表型。提出了后续实验来识别负责这些突变表型的神经元。