Natural Variation in a Dendritic Scaffold Protein Remodels Experience-Dependent Plasticity by Altering Neuropeptide Expression

Neuron. 2020 Jan 8;105(1):106-121.e10. doi: 10.1016/j.neuron.2019.10.001. Epub 2019 Nov 19.


The extent to which behavior is shaped by experience varies between individuals. Genetic differences contribute to this variation, but the neural mechanisms are not understood. Here, we dissect natural variation in the behavioral flexibility of two Caenorhabditis elegans wild strains. In one strain, a memory of exposure to 21% O2 suppresses CO2-evoked locomotory arousal; in the other, CO2 evokes arousal regardless of previous O2 experience. We map that variation to a polymorphic dendritic scaffold protein, ARCP-1, expressed in sensory neurons. ARCP-1 binds the Ca2+-dependent phosphodiesterase PDE-1 and co-localizes PDE-1 with molecular sensors for CO2 at dendritic ends. Reducing ARCP-1 or PDE-1 activity promotes CO2 escape by altering neuropeptide expression in the BAG CO2 sensors. Variation in ARCP-1 alters behavioral plasticity in multiple paradigms. Our findings are reminiscent of genetic accommodation, an evolutionary process by which phenotypic flexibility in response to environmental variation is reset by genetic change.

Keywords: Caenorhabditis elegans, carbon dioxide sensing; experience-dependent plasticity; genetic accommodation; natural variation; neuropeptide; oxygen sensing.

Publication types

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

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Arousal / drug effects
  • Behavior, Animal / drug effects
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Carbon Dioxide / pharmacology
  • Dendrites / metabolism*
  • Female
  • Individuality
  • Neuronal Plasticity / physiology*
  • Neuropeptides / biosynthesis*
  • Phosphoric Diester Hydrolases / metabolism
  • Polymorphism, Genetic
  • Sensory Receptor Cells / metabolism
  • Signal Transduction / physiology*
  • Species Specificity


  • Caenorhabditis elegans Proteins
  • Neuropeptides
  • Carbon Dioxide
  • Phosphoric Diester Hydrolases