Sumathipala, Sureni Khan, Suha Rey, Celine A Kozol, Robert Dallman, Julia E. Sensory induced hyperactivity in a syngap1ab zebrafish models of ASD <p>My project uses zebrafish to test how loss of function mutations in Synaptic Ras-GTPase Activating Protein 1 (<i>SYNGAP1</i>) impact neural circuit function. SYNGAP1 is a component of the postsynaptic density of glutamatergic synapses and plays an essential role in receptor trafficking and synaptic strengthening allied with learning and memory. In our lab, we have generated stable <i>syngap1ab </i>mutant zebrafish models of ASD using CRISPR/Cas 9 genome editing. Using these models, we are quantifying ASD-relevant behaviors with the ultimate goal of delineating the neural-circuit-level mechanisms underlying those behaviors.</p> <p>Due to sensory-induced hyperactivity observed in humans with heterozygous <i>SYNGAP1 </i>loss-of-function variants, we tested <i>syngap1ab<sup>+/-</sup></i>zebrafish mutants to see whether they would be similarly hyperactive in response to light and/or sound (tap) stimuli. We found that the <i>syngap1ab<sup>+/-</sup> </i>mutants do exhibit hyperactivity in response to both light and tap stimuli at six days post-fertilization. Our kinematic data from <i>syngap1ab </i><sup>+/-</sup> larvae show a significant increase in swim velocities when tapped, and increased duration of swim bouts compared to WT larvae with no alterations associated with swim coordination. Taken together, these results suggest that possible involvement of Syngap1<i> </i>in the early development of sensory-motor integration in the zebrafish.</p> SYNGAP1;ASD candidate genes;sensory processing difficulties;zebrafish models;Behavioral Neuroscience;Genetics;Neurogenetics 2020-04-20
    https://tagc2020.figshare.com/articles/poster/Sensory_induced_hyperactivity_in_a_syngap1ab_zebrafish_models_of_ASD/12150504
10.6084/m9.figshare.12150504.v1