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Eviatar Yemini¹, Albert Lin², Amin Nejatbakhsh³, Erdem Varol³, Ruoxi Sun³, Gonzalo E Mena⁴, Aravinthan D T Samuel², Liam Paninski³, Vivek Venkatachalam⁵, Oliver Hobert⁶

1. Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA. Electronic address: eiy1@columbia.edu.
2. Department of Physics, Center for Brain Science, Harvard University, Cambridge, MA 02138, USA.
3. Departments of Statistics and Neuroscience, Grossman Center for the Statistics of Mind, Center for Theoretical Neuroscience, Zuckerman Institute, Columbia University, New York, NY 10027, USA.
4. Department of Statistics and Data Science Initiative, Harvard University, Cambridge, MA 02138, USA.
5. Department of Physics, Northeastern University, Boston, MA 02115, USA.
6. Department of Biological Sciences, Howard Hughes Medical Institute, Columbia University, New York, NY 10027, USA.

Abstract

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.

Presented By Eviatar Yemini | ORCID iD | Lab Website