The calcium-sensing receptor (CaSR) regulates zebrafish sensorimotor decision making via a genetically defined cluster of hindbrain neurons.

Decision making is a fundamental nervous system function that ranges widely in complexity and speed of execution. We previously established larval zebrafish as a model for sensorimotor decision making and identified the G-protein-coupled calcium-sensing receptor (CaSR) to be critical for this process. Here, we report that CaSR functions in neurons to dynamically regulate the bias between two behavioral outcomes: escapes and reorientations. By employing a computational guided transgenic strategy, we identify a genetically defined neuronal cluster in the hindbrain as a key candidate site for CaSR function. Finally, we demonstrate that transgenic CaSR expression targeting this cluster consisting of a few hundred neurons shifts behavioral bias in wild-type animals and restores decision making deficits in CaSR mutants. Combined, our data provide a rare example of a G-protein-coupled receptor that biases vertebrate sensorimotor decision making via a defined neuronal cluster.