RRC ID 75748
Author Jain RA, Wolman MA, Marsden KC, Nelson JC, Shoenhard H, Echeverry FA, Szi C, Bell H, Skinner J, Cobbs EN, Sawada K, Zamora AD, Pereda AE, Granato M.
Title A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making.
Journal Curr Biol
Abstract 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.
Volume 28(9)
Pages 1357-1369.e5
Published 2018-5-7
DOI 10.1016/j.cub.2018.03.025
PII S0960-9822(18)30354-3
PMID 29681477
PMC PMC5940496
MeSH 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*
IF 9.601
Zebrafish hspGFFDMC130A hspGFF62A