PUBLICATION
A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making
- Authors
- 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.
- ID
- ZDB-PUB-180424-2
- 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.
Citation
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. (2018) A Forward Genetic Screen in Zebrafish Identifies the G-Protein-Coupled Receptor CaSR as a Modulator of Sensorimotor Decision Making. Current biology : CB. 28(9):1357-1369.e5.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping