Circuit analysis of the Calcium-Sensing Receptor (CaSR) in sensorimotor decision-making in the larval zebrafish

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Degree type
PhD
Graduate group
Neuroscience
Discipline
Neuroscience and Neurobiology
Genetics and Genomics
Biology
Subject
behavioral choice
calcium-sensing receptor
decision-making
sensorimotor
zebrafish
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Copyright date
01/01/2022
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Author
Shoenhard, Hannah, Margaret
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Abstract

A central doctrine in neurogenetics is that genetic mutations alter development and functioning of the cells that comprise neural circuits, thereby resulting in behavioral phenotypes. However, discovering the circuit mechanisms by which genetic changes result in aberrant behavior remains a significant obstacle in the field. In particular, while larval zebrafish are a widely-used model in neurogenetic studies, identifying the specific circuit elements where genes function to influence behavior has proven a major technical challenge in this organism. In particular, we have established larval zebrafish as a model organism for acoustically-evoked sensorimotor decision-making and identified a critical role for the Calcium Sensing Receptor, a conserved vertebrate G protein-coupled receptor, in this process. We developed a whole-brain unbiased computational method, Multivariate Analysis of Variegated Expression in Neurons (MAVEN), to identify a specific hindbrain neuronal population via which CaSR regulates a sensorimotor decision. We demonstrate that CaSR acts acutely in a neuronal population outside the canonical circuits involved in the sensorimotor decision, and set the stage for further elucidation of the functional role of this population in decision-making. We also validate the use of MAVEN for identifying brain loci where genetic function regulates behavior, establishing a tool to advance understanding of how genetic changes lead to circuit and behavioral dysfunction.

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Granato, Michael
Date of degree
2022
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