Sensory induced hyperactivity in a syngap1ab zebrafish models of ASD

My project uses zebrafish to test how loss of function mutations in Synaptic Ras-GTPase Activating Protein 1 (SYNGAP1) 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 syngap1ab 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.

Due to sensory-induced hyperactivity observed in humans with heterozygous SYNGAP1 loss-of-function variants, we tested syngap1ab+/-zebrafish mutants to see whether they would be similarly hyperactive in response to light and/or sound (tap) stimuli. We found that the syngap1ab+/- mutants do exhibit hyperactivity in response to both light and tap stimuli at six days post-fertilization. Our kinematic data from syngap1ab +/- 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 in the early development of sensory-motor integration in the zebrafish.