From Swimming to Seizures: Investigating Motor Behavior and Epilepsy in Developing Zebrafish

Department of Biology Seminar Series
Dr. Gerald Downes, Biology Department, University of Massachusetts in Amherst
- | Claire Fagin Hall Auditorium
Gerald Downes

Hosted by Dr. Marc Schmidt

Home institution: Biology Department, University of Massachusetts in Amherst

GABAA receptors mediate rapid responses to the neurotransmitter GABA and are robust regulators of the brain and spinal cord neural networks that control locomotor behaviors, such as walking and swimming. In developing zebrafish, pharmacological blockade of these receptors causes hyperactive swimming, which is also a feature of many zebrafish epilepsy models. Although GABAA receptors are important to control locomotor behavior, the large number of subunits and homeostatic compensatory mechanisms have challenged efforts to determine subunit-selective roles. To address this issue, we mutated zebrafish GABAA subunit genes individually and in pairs using a CRISPR-Cas9 somatic inactivation approach, then we analyzed the swimming behavior of developing larvae. We found that disrupting the expression of specific pairs of subunits resulted in different hyperactive swimming behaviors in early larval stages. However, abnormal swimming phenotypes were nearly absent at later larval stages, suggesting that homeostatic mechanisms during development were able to overcome the disruption of even multiple subunits. Taken together, this study identifies GABAA receptors that regulate locomotor behavior, and also suggests an approach to continuing probing epilepsy genetics.  

Dr. Downes was recently featured on the Story Collider podcast. You can listen to it here


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