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

作者：Jain Roshan A^*; Wolman Marc A; Marsden Kurt C; Nelson Jessica C; Shoenhard Hannah; Echeverry Fabio A; Szi Christina; Bell Hannah; Skinner Julianne; Cobbs Emilia N; Sawada Keisuke; Zamora Amy D; Pereda Alberto E; Granato Michael^*

来源：Current Biology, 2018, 28(9): 1357-+.

DOI：10.1016/j.cub.2018.03.025

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 G alpha(i/o) and G alpha(q/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.

• 出版日期2018-5-7