Effects of Altered GABA Neurotransmission on Early Development in Zebrafish

Science Center, Bent Corridor

Alterations in GABAergic neuron function and associated inhibitory neural circuitry has been implicated with many neurodevelopmental disorders, including autism spectrum disorder (ASD) and epilepsy. Further understanding GABA neuron functionality during neurodevelopment may be important to determining molecular mechanisms underlying neurological disorders and developing novel therapeutics. The purpose of this research is to characterize how manipulating GABA neurotransmission during early development affects brain formation and function. Zebrafish embryos are being treated with chemicals that block or activate GABA receptors at different dosages and time points; embryos are then assessed for morphological and molecular phenotypes as well as survivability. By determining the lethal dosage of treatment i.e. survivability, a sub-lethal dosage can be identified where morbid morphological changes occur. Identifying the phenotypes of neurodevelopmental GABA alteration can inform additional analyses of genetic and environmental factors associated with ASD and other neurological disorders(e.g. factors that produce similar phenotypes may affect GABA neuron development). This manipulation was carried out through titration treatments and imaging with a brightfield microscope. The preliminary findings indicate that the GABA system of the developing zebrafish is resistant to lower dosages of the GABA-a receptor antagonist, bicuculline, which was used in the titration treatments.