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是如何组装的，这仍然是一个核心的未解决的问题， 神经科学寻找控制神经回路中突触连接特异性的基因 将是最终操纵电路元件和促进功能的关键之一。 损伤后再生。然而，阐明电路连接性对于一个半导体制造商来说是具有挑战性的。 原因很多，包括电路本身的复杂性，功能的问题， 在许多系统中，基因工具的冗余和稀缺， 定义的神经元子集的活动。该项目使用了一种新颖的方法， 果蝇的先进遗传学来定义一个足以驱动运动行为的神经回路， 简单到我们可以确定相关的突触连接并识别基因 控制其发展。使用温度敏感突变，shibirets 1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 神经系统的突触将被灭活。通过将突触活动添加回选定的子集 通过靶向表达野生型shibire+，一个最小的中间神经元回路， 具有感觉和运动神经元，能够产生运动输出。很长的- 本计画的长期目标是发展果蝇幼虫的运动模式系统，以供研究 电路开发考虑到神经系统发育和功能在脑内的保存， 在动物界，果蝇神经回路突触连接的许多规则 在发展过程中，很可能直接适用于了解发展， 哺乳动物的电路

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.