Autism Spectrum Disorder (ASD) is an extremely common disorder in which approximately 1 in 59 kids in the US are diagnosed; it is four times more prevalent in males than females. ASD involves a broad range of conditions related to neurological development and is often associated with cognitive and social behavior deficits. Some individuals also suffer from intellectual disability and epilepsy. The conditions greatly vary between individuals because of the vast number of genes that when mutated lead to characteristics related to autism. This ultimately leads to a wide spectrum of conditions; however, it is noticeable that social behavior deficits is the most common characteristics across the spectrum.
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Danio rerio, more commonly known as zebrafish, is the perfect model organism to test for social behavior deficits. They have similar brain structures to that of humans shown to be important in social behavior such as the hippocampus, amygdala, and cerebellum. Additionally, zebrafish possess an inherent social behavior known as shoaling in which they swim in close proximity. However, when zebrafish possess a social behavior deficit they swim outside of the shoal. The distance can then be measured to quantify severity in social behavior impairments.
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Next, I will look at what other genes are up or down regulated when SYNGAP1 is mutated in the brain. Because I want this study to completely focus on social behavior I will use male fish only thus excluding any differences that may be due to gender. To do this I will acquire the same brain tissue samples from all fish; specifically, the hippocampus, amygdala and cerebellum will be selected. The brain samples will be used for RNA-seq. I expect the serine 839 mutants will show similar results to wildtype fish as this conserved phosphorylation site most likely has a function outside of the nervous system.
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Some of my future directions include expanding the third aim to include the serine 861 mutants because it would be interesting to see if this phosphorylation site actually does play a role in neurons only or if when mutated it changes the interactions in sexual organs as well. Additionally, it would be interesting to test different age fish because ASD characteristics actually change over time in an individuals life, along with their sexual organs, so I think looking at these differences over time would be extremely interesting and possibly reveal more insight into social behavior changes. Applying a very similar study to repetitive behaviors, instead of only social behavior, would be of interest as this is another extremely common characteristic associated with ASD. Lastly, I believe a long term future direction would be improving the overall understanding of social behavior in the brain. It is currently unknown exactly how the brain's genes and proteins alter individual behaviors, so creating a more extensive map of this process would be beneficial for all future studies related to behavior.
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Draft 1 |
Final Presentation Draft |
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