Genetic dissection of locomotion

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：动物必须以刻板和有节奏的方式同步无数的肌肉屈曲和伸展事件。运动协调的核心是中央模式发生器（CPG），这是一种神经回路，能够从相对简单的非节奏输入中产生有节奏的输出。虽然存在大量的功能证据的运动和非运动的CPGs，细胞成分的CPGs介导协调运动在更复杂的系统仍然在很大程度上不确定。此外，运动CPG活动如何相互整合，并通过下行和感觉输入进行修改，在细胞水平上也是未知的。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，也是所研究行为复杂性的结果。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的现有努力，使用果蝇中可用的强大遗传工具来表征运动神经回路， 果蝇在这项提案中，一种新的，高分辨率的测定，定量测量果蝇模型中的几十个行走参数将被用来筛选特定的突变表型，发生的结果激活和/或抑制神经元的子集的神经活动。后续的实验，提出了确定的神经元，负责这些突变的表型。

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.