A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making

Curr Biol. 2018 May 7;28(9):1357-1369.e5. doi: 10.1016/j.cub.2018.03.025. Epub 2018 Apr 19.


Animals continuously integrate sensory information and select contextually appropriate responses. Here, we show that zebrafish larvae select a behavioral response to acoustic stimuli from a pre-existing choice repertoire in a context-dependent manner. We demonstrate that this sensorimotor choice is modulated by stimulus quality and history, as well as by neuromodulatory systems-all hallmarks of more complex decision making. Moreover, from a genetic screen coupled with whole-genome sequencing, we identified eight mutants with deficits in this sensorimotor choice, including mutants of the vertebrate-specific G-protein-coupled extracellular calcium-sensing receptor (CaSR), whose function in the nervous system is not well understood. We demonstrate that CaSR promotes sensorimotor decision making acutely through Gαi/o and Gαq/11 signaling, modulated by clathrin-mediated endocytosis. Combined, our results identify the first set of genes critical for behavioral choice modulation in a vertebrate and reveal an unexpected critical role for CaSR in sensorimotor decision making.

Keywords: AP2S1; CaSR; behavior choice; calcium-sensing receptor; decision making; genetic screen; startle response; zebrafish.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Behavior, Animal
  • Calcium / metabolism
  • Choice Behavior / physiology*
  • Genetic Testing
  • Mutation*
  • Psychomotor Performance*
  • Receptors, Calcium-Sensing / genetics
  • Receptors, Calcium-Sensing / physiology*
  • Zebrafish / embryology
  • Zebrafish / physiology*
  • Zebrafish Proteins / genetics
  • Zebrafish Proteins / physiology*


  • Receptors, Calcium-Sensing
  • Zebrafish Proteins
  • casr protein, zebrafish
  • Calcium