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：动物必须以刻板且有节奏的方式同步无数的肌肉屈曲和伸展活动。运动协调的核心是中枢模式发生器（CPG），这种神经回路能够从相对简单的非节律输入产生节律输出。尽管存在大量关于运动和非运动 CPG 的功能证据，但在更复杂的系统中介导协调运动的 CPG 的细胞成分仍然很大程度上未定义。此外，运动 CPG 活动如何相互整合并通过下降和感觉输入进行修改在细胞水平上也很大程度上未知。我们知识中的这些差距可能不仅是由于神经回路的复杂性，也是由于所研究的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，以利用果蝇中可用的强大遗传工具来表征运动神经回路， 黑腹果蝇。在该提案中，一种新颖的高分辨率测定方法将定量测量果蝇模型中的数十个行走参数，用于筛选由于激活和/或抑制神经元亚群中的神经活动而出现的特定突变表型。建议进行后续实验来鉴定导致这些突变表型的神经元。