Journal
CELL
Volume 184, Issue 1, Pages 272-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2020.12.012
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Funding
- NIH Office of Research Infrastructure Programs [P40 OD010440]
- Harvard MRSEC [DMR-1420570]
- Howard Hughes Medical Institute
- NSF-CRCNS Award [1912194]
- NIH [5T32DK7328-37, 5T32DK007328-35, 5T32MH015174-38, 5T32MH015174-37, 1R01NS113119-01]
- NIBIB [R01 (EB22913)]
- NSF NeuroNex Award [DBI-1707398]
- Simons Collaboration on the Global Brain
- Gatsby Charitable Foundation
- Harvard Data Science Initiative Postdoctoral Fellowship
- NSF [IOS-1452593]
- NSF Physics of Living Systems Graduate Student Research Network [1806818]
- Burroughs Wellcome Fund Career Award at the Scientific Interface
- Division Of Physics
- Direct For Mathematical & Physical Scien [1806818] Funding Source: National Science Foundation
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NeuroPAL is a multicolor transgene that helps resolve neuronal identities in C. elegans. It can be used with various reporters of gene expression or neuronal dynamics and has been utilized in studies related to metabotropic receptor expression, cell fate changes, and brainwide activity in response to chemosensory cues.
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.
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