EAGER: Targeted disruption of neural processes in zebrafish using femtosecond laser pulses to dissect the functional anatomy of the nervous system

1050134Schaffer阐明系统部分功能的一种方法是破坏和打破该部分并观察其效果。例如，利用分子生物学工具，这种方法通过对敲除和敲入转基因动物的研究，使人们更好地了解了许多疾病的遗传起源。虽然这种基因操纵技术非常先进，但物理破坏技术，特别是非常精细或难以进入的结构，仍然很粗糙。开发技术，使特定的目标结构被破坏亚微米空间精度，没有显着的附带影响，并在本地，在体内环境将打开大门，各种研究，可以匹配的影响转基因实验。飞秒激光脉冲具有将能量存款到透明材料块体中的微观体积中而不影响材料表面的独特能力。PI建议开发和使用这种能力来破坏活体动物神经系统中的特定靶向结构，目的是阐明功能。特别是，研究行为的神经基础，通过解剖神经回路，通过削减个别轴突和树突在斑马鱼后脑。

1050134SchafferOne way to elucidate the function of part of a system is to disrupt and break that part and observe the effect. Using molecular biology tools, this method has led to a better understanding of the genetic origins of many diseases through studies of knock-out and knock-in transgenic animals, for example. While such genetic manipulation technologies are very advanced, techniques for physical disruption, especially of very fine-scale or difficult to access structures, remain crude. Development of technologies that allow specifically targeted structures to be disrupted with sub-micrometer spatial precision, without significant collateral effects, and in native, in vivo environments would open the door to a variety of studies that could match the impact transgenic experiments have had. Femtosecond laser pulses have the unique capability to deposit energy into a microscopic volume in the bulk of a transparent material without affecting the surface of the material. The PI proposes to develop and use this capability to disrupt specifically targeted structures in the nervous system of live animals with the goal of elucidating function. In particular, to study the neural basis of behavior by dissecting neural circuits through cuts to individual axons and dendrites in zebrafish hindbrain.