NeuroPAL: A Multicolor Atlas for Whole-Brain Neuronal Identification in C. elegans

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.

Keywords: C. elegan; atlas; expression pattern; nervous system; whole nervous sytem imaging.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Algorithms
  • Anatomic Landmarks
  • Animals
  • Atlases as Topic*
  • Brain / physiology*
  • Brain Mapping*
  • Caenorhabditis elegans / physiology*
  • Cell Body / physiology
  • Cell Lineage
  • Drosophila / physiology
  • Mutation / genetics
  • Nerve Net / physiology
  • Neurons / physiology*
  • Phenotype
  • Receptors, Metabotropic Glutamate / metabolism
  • Receptors, Neurotransmitter / metabolism
  • Smell / physiology
  • Software*
  • Taste / physiology
  • Transcription Factors / metabolism
  • Transgenes


  • Receptors, Metabotropic Glutamate
  • Receptors, Neurotransmitter
  • Transcription Factors