ZFIN ID: ZDB-PUB-180424-2
A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making
Jain, R.A., Wolman, M.A., Marsden, K.C., Nelson, J.C., Shoenhard, H., Echeverry, F.A., Szi, C., Bell, H., Skinner, J., Cobbs, E.N., Sawada, K., Zamora, A.D., Pereda, A.E., Granato, M.
Date: 2018
Source: Current biology : CB   28(9): 1357-1369.e5 (Journal)
Registered Authors: Granato, Michael, Jain, Roshan, Marsden, Kurt, Wolman, Marc
Keywords: AP2S1, CaSR, behavior choice, calcium-sensing receptor, decision making, genetic screen, startle response, zebrafish
MeSH Terms:
  • Acoustic Stimulation
  • Animals
  • Behavior, Animal
  • Calcium/metabolism
  • Decision Making*
  • Genetic Testing
  • Mutation*
  • Psychomotor Performance*
  • Zebrafish/embryology
  • Zebrafish/physiology*
PubMed: 29681477 Full text @ Curr. Biol.
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.