Massively Parallel Brain Imaging

我提出了一种颠覆性的技术，它将彻底改变我们对大脑功能的理解， 发展和疾病。由于神经回路的研究仍然受到缺乏 数据，我们需要大规模并行的方法来进行大脑成像，这将提高数据采集率， 超过两个数量级。高通量技术已经彻底改变了某些领域 基因组学和蛋白质组学等生物学的发展，但神经科学还没有经历一个井喷式的增长 规模相当。我将建造仪器，使大脑体积约100警报 苍蝇同时成像的双光子荧光显微镜。我选择了果蝇， 黑腹果蝇，因为它的大脑很小，有着复杂的行为， 基因靶向改变脑回路的菌株数量，荧光的实用性 在这个物种的神经活动的成像，以及苍蝇作为研究模型的重要性， 许多脑部疾病。 大规模并行脑成像将开辟全新的途径：1）跟踪神经元的能力 在大量正常果蝇和那些遗传诱导的神经系统疾病的果蝇的大脑中， 电路扰动将彻底改变我们对神经电路如何产生动物 行为; 2）果蝇作为研究发育的模型系统的现在突出的作用 疾病，神经退行性疾病和成瘾意味着我们将获得重要的医学见解 3）我们的技术将在药物筛选方面有重要的应用， 允许在体内快速评估新化合物的细胞效应; 4）执行 在果蝇胚胎成熟过程中对细胞事件进行高通量延时成像， 发育神经生物学的又一次革命我们技术的应用也将 在线虫和斑马鱼等其他模式生物中大量存在，深刻影响了多种生物， 生物医学领域。

I propose a disruptive technology that will revolutionize our understanding of brain function, development, and disease. Because the study of neural circuits remains deeply limited by a paucity of data, we need massively parallel approaches to brain imaging that will raise data acquisition rates by over two orders of magnitude. High-throughput technologies have already revolutionized certain areas of biology such as genomics and proteomics, but neuroscience has yet to experience a growth spurt of comparable magnitude. I will construct instrumentation allowing the brain volumes of ~100 alert flies to be imaged simultaneously by two-photon fluorescence microscopy. I have chosen the fruit fly, Drosophila melanogaster, because of its small brain, its sophisticated behavioral repertoire, the large number of strains with genetically targeted alterations to brain circuitry, the utility of fluorescence imaging of neural activity in this species, and the importance of the fly as a model for the study of many brain diseases. Massively parallel brain imaging will open entirely new avenues: 1) The ability to track neural dynamics across the brains of large numbers of normal flies and those with genetically induced neural circuit perturbations will revolutionize our understanding of how neural circuits produce animal behavior; 2) The now prominent role of the fruit fly as a model system for the study of developmental disorders, neurodegenerative diseases, and addiction implies we will gain significant medical insights into devastating conditions; 3) Our technology will have important applications to drug screening, allowing the cellular effects of new compounds to be assessed rapidly in vivo; 4) The ability to perform high-throughput time-lapse imaging of cellular events during the maturation of fly embryos will allow an additional revolution in developmental neurobiology. Applications of our technology will also be plentiful in other model organisms such as nematodes and zebrafish, profoundly impacting multiple areas of biomedicine.