Drosophila larval locomotion as a model for studying neural circuit development

项目摘要 神经回路在发育过程中如何组装仍然是一个核心的悬而未决的问题 神经科学。寻找控制回路内突触连接特异性的基因 将是最终操纵电路组件并促进功能的关键之一 受伤后的再生。然而，阐明电路连接一直是一个具有挑战性的 原因有很多，包括电路本身的复杂性、功能问题 许多系统中基因工具的冗余和稀缺性，以操纵发育和 已定义的神经元亚群的活性。这个项目使用了一种新的方法，它利用了 果蝇的高级遗传学定义了足以驱动运动行为的神经回路，但 足够简单，我们可以确定相关的突触连接和识别基因 控制它的发展。使用对温度敏感的突变，Shibirets1有条件地 在高温下阻断突触传递，相对简单的幼虫内的神经元 神经系统将被突触灭活。通过将突触活动重新添加到选定的子集 通过靶向表达野生型Shibire+，这是一种最小的中间神经元回路 有了感觉和运动神经元，就能识别出能够产生运动输出的神经元。长的- 该项目的学期目标是开发果蝇幼虫运动作为研究的模式系统 电路开发。考虑到神经系统发育和功能的保守性 动物王国，果蝇神经回路突触连接的许多规则 很可能直接适用于理解 哺乳动物的环路。

Project Summary How neural circuits are assembled during development remains a central unsolved problem in the neurosciences. Finding the genes that control the specificity of synaptic connections within circuits will be one of the keys to eventually manipulating circuit components and promoting functional regeneration following injury. However, elucidating circuit connectivity has been challenging for a number of reasons, including the complexity of the circuits themselves, issues of functional redundancy and the scarcity of genetic tools in many systems to manipulate the development and activity of defined neuronal subsets. This project uses a novel approach that capitalizes on the advanced genetics of Drosophila to define a neural circuit sufficient to drive locomotor behavior, but simple enough that we can determine the relevant synaptic connections and identify the genes controlling its development. Using a temperature-sensitive mutation, shibirets1 that conditionally blocks synaptic transmission at elevated temperatures, neurons within the relatively simple larval nervous system will be synaptically inactivated. By adding back synaptic activity to selected subsets of neurons by targeted expression of wild-type shibire+, a minimal circuit of interneurons, together with sensory and motor neurons, capable of generating motor output will be identified. The long- term goal of this project is to develop Drosophila larval locomotion as a model system for studying circuit development. Given the conservation of nervous system development and function within the animal kingdom, many of the rules by which neural circuits in Drosophila are synaptically connected during development are likely to be directly applicable to understanding the development of mammalian circuits.