Zebrafish Models of Autism Spectrum Disorder

Psychiatric disorders necessarily have their origins in the dysfunction or loss of neural circuitry.  Our lab has recently begun modelling Autism Spectrum Disorder (ASD) by mutating genes linked to ASD in humans.  The strength of the zebrafish model system is that it permits access to the functioning brain, thus allowing analyses of developmental dynamics, population-level neural coding, and synapse dynamics in vivo.

With the help of grants from the Simons Foundation Autism Research Initiative (SFARI), we have laid the groundwork for studying sensory processing defects in zebrafish models of ASD. This work involves brain-wide imaging of sensory processing, sensory integration, and sensorimotor gating in several mutant lines of zebrafish as they perceive, process, and react to a wide range of visual, auditory, and vestibular stimuli. The goal is to identify the specific circuit- and network-level changes in their sensory systems that could underlie their behavioural deficits.

Thus far we have described alterations in the connectivity of the auditory and visual processing networks in the fmr1 model of ASD and fragile X syndrome. We have shown that habituation to a visual loom stimulus is slower in the fmr1 fish (Marquez-Legorreta et al., 2019), and connectivity within the auditory system is higher at lower volumes of sound in the fmr1 fish (Constantin et al., 2019). Both of these findings point towards increased sensitivity in the sensory processing pathways of this fish, which is consistent with human phenotypes and lays the groundwork for further investigation.

In the ongoing work, we’re doing more detailed analyses of sensory networks in fmr1 animals, and are extending these analyses to a suite of other mutants in other ASD-linked genes.