1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2] Janelia Farm Research Campus, Howard Hughes Medical Institute, Ashburn, Virginia, USA. [3].
1] Research Institute of Molecular Pathology, Vienna Biocenter, Vienna, Austria. [2] Automation and Control Institute, Vienna University of Technology, Vienna, Austria. [3].
Nat Methods. 2014 Jul;11(7):756-62. doi: 10.1038/nmeth.2973. Epub 2014 May 25.
Rapidly and selectively modulating the activity of defined neurons in unrestrained animals is a powerful approach in investigating the circuit mechanisms that shape behavior. In Drosophila melanogaster, temperature-sensitive silencers and activators are widely used to control the activities of genetically defined neuronal cell types. A limitation of these thermogenetic approaches, however, has been their poor temporal resolution. Here we introduce FlyMAD (the fly mind-altering device), which allows thermogenetic silencing or activation within seconds or even fractions of a second. Using computer vision, FlyMAD targets an infrared laser to freely walking flies. As a proof of principle, we demonstrated the rapid silencing and activation of neurons involved in locomotion, vision and courtship. The spatial resolution of the focused beam enabled preferential targeting of neurons in the brain or ventral nerve cord. Moreover, the high temporal resolution of FlyMAD allowed us to discover distinct timing relationships for two neuronal cell types previously linked to courtship song.
快速而有选择性地调节自由活动动物中特定神经元的活动，是研究影响行为的神经回路机制的有力方法。在黑腹果蝇中，温度敏感的沉默子和激活子被广泛用于控制遗传定义的神经元细胞类型的活性。然而，这些热遗传方法的一个局限性是其时间分辨率较差。在这里，我们介绍了 FlyMAD（果蝇思维改变装置），它可以在几秒钟甚至几分之一秒内实现热遗传沉默或激活。使用计算机视觉，FlyMAD 将红外激光瞄准自由行走的果蝇。作为原理验证，我们演示了参与运动、视觉和求偶的神经元的快速沉默和激活。聚焦光束的空间分辨率使得大脑或腹神经索中的神经元能够被优先靶向。此外，FlyMAD 的高时间分辨率使我们能够发现以前与求偶歌曲相关的两种神经元细胞类型之间的不同时间关系。
