The Behavioral Study of Autism in Zebrafish

According to the Centers of Disease Control and Prevention (CDC) in 2014, it was recorded that 1 in 68 children in the United States have autism spectrum disorder (ASD). Autism is a genetic disorder caused by extra or missing genes in an individual’s DNA. With over 18 genes that genetically link to the development of neurological dysfunction, researchers have concluded that there is a relationship between Topoisomerase 3b (top3b) to this neurodevelopmental disorder, as well as, schizophrenia (Stoll, G. et al. 2013). Top3b gene codes for an enzyme that maintains the structure of mRNA and allows for efficient translation by the ribosomes. If this gene is not present or mutated, there will be complications in transcription, therefore causing error in the development of brain function (Xu, D. et al. 2013). Understanding the role top3b plays in the early development of the brain will make the latter stages of development better explainable. The objectives of this research are to look at the zebrafish (Danio rerio) and create an animal model to study the behavioral changes caused by this gene deficiency. An animal model is used primarily because in the early embryonic stages, the fish cannot feel pain. Zebrafish are also very similar to humans and acquire the same types of genes with the similar targets. Also, ASD presents in the early stages of brain development, furthering the use of this testable, yet ethical model. The procedure consists of injecting a one-cell zebrafish embryo with top3b antisense nucleotides to cause a gene deficiency in the zebrafish larvae. These larvae will be used to study the fish’s behavior over a 4-5 day period. The fish will be monitored using Daniovision and data will be recorded using EthoVision XT. A flashing light stimulus will be set in order to cause a reaction in the embryos. I will measure the velocity as well as the locomotive behavior of these gene deficient larvae. Behaviors such as, how far they travel, how fast they travel and the patterns they follow will be recorded. I will then compare and contrast the control group of embryos and the deficient embryos to see the behavioral differences between the two. I expect to see a measurable difference in the behavior of the genetically deficient larvae, when compared to the control group of larvae. The behavioral changes exhibited will then be related back to the cell molecular changes in order to connect the two. Whenever the behavioral defects of this gene is known, then there will be an idea about which region of the brain is used, as well as, the neurons and circuits that are involved