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
|
Resource |
Zebrafish |
hspGFFDMC130A
hspGFF62A |