Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA.
Department of Physics, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
Cell. 2021 Jan 7;184(1):272-288.e11. doi: 10.1016/j.cell.2020.12.012. Epub 2020 Dec 29.
Comprehensively resolving neuronal identities in whole-brain images is a major challenge. We achieve this in C. elegans by engineering a multicolor transgene called NeuroPAL (a neuronal polychromatic atlas of landmarks). NeuroPAL worms share a stereotypical multicolor fluorescence map for the entire hermaphrodite nervous system that resolves all neuronal identities. Neurons labeled with NeuroPAL do not exhibit fluorescence in the green, cyan, or yellow emission channels, allowing the transgene to be used with numerous reporters of gene expression or neuronal dynamics. We showcase three applications that leverage NeuroPAL for nervous-system-wide neuronal identification. First, we determine the brainwide expression patterns of all metabotropic receptors for acetylcholine, GABA, and glutamate, completing a map of this communication network. Second, we uncover changes in cell fate caused by transcription factor mutations. Third, we record brainwide activity in response to attractive and repulsive chemosensory cues, characterizing multimodal coding for these stimuli.
全面解析全脑图像中的神经元特征是一项重大挑战。我们通过构建一种名为 NeuroPAL（神经元多色图谱地标）的多色转基因来实现这一目标。NeuroPAL 线虫具有整个雌雄同体神经系统的典型多色荧光图谱，可以解析所有神经元特征。用 NeuroPAL 标记的神经元在绿色、青色或黄色发射通道中没有荧光，这使得该转基因能够与许多基因表达或神经元动力学报告基因一起使用。我们展示了三个利用 NeuroPAL 进行全神经系统神经元鉴定的应用。首先，我们确定了乙酰胆碱、GABA 和谷氨酸所有代谢型受体的全脑表达模式，完成了这个通讯网络图谱。其次，我们揭示了转录因子突变引起的细胞命运变化。最后，我们记录了对有吸引力和排斥性化学感觉线索的全脑活动，对这些刺激进行了多模态编码。
