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

Cell Rep. 2022 Dec 6;41(10):111790. doi: 10.1016/j.celrep.2022.111790.

Abstract

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.

Keywords: CP: Neuroscience; CaSR; LLC; Mauthner; SLC; behavioral choice; circuit; decision making; neurogenetics; sensorimotor; startle response.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Receptors, Calcium-Sensing* / genetics
  • Zebrafish* / genetics

Substances

  • Receptors, Calcium-Sensing