Drugs prescribed in Phelan-McDermid Syndrome differentially impact sensory behaviors in shank3 zebrafish models

Altered sensory processing is a pervasive symptom in individuals with Autism Spectrum Disorders (ASD). Especially in cases of profound autism, individuals are often medicated to manage behaviors like aggression and/or self-harm and/or epilepsy, and it remains unclear how these medications might impact perception/sensory processing. To test this, we screened three medications, risperidone, Lithium Chloride (LiCl), and carbamazepine (CBZ), prescribed to individuals with Phelan-McDermid Syndrome (PMS) and one drug, 2-Methyl-6-(phenylethynyl) pyridine (MPEP) tested in rodent models of PMS, for their effects on a sensory-induced behavior in two zebrafish PMS models with frameshift mutations in the N- or C- termini. PMS is caused by deletions of the terminal end of chromosome 22 or point mutations in Shank3. People with PMS can present with an array of symptoms including ASD, epilepsy, gastrointestinal distress, and reduced responses to sensory stimuli. Our zebrafish mutant shank3ab models li..., High-throughput behavioral screens
Behavioral experiments were performed using the DanioVision systemtm (Noldus, Wageningen, NTD) with the DanioVision observation chamber (DVOC-0040). Videos were collected at 25 fps with 1280 x 960 resolution using a Basler acA1300-60gm camera fitted with a 12 mm Megapixel lens. All DanioVision experiments were run using an ANSI SBS compatible 96 well microtiter plate. Data were collected and analyzed using the DanioVision EthoVision XT  software version 11.5 (Noldus). White light for the visual motor response assay was set at 12% intensity on the high-power setting. Six-day-old larvae were acclimated to the observation chamber at 28°C in the dark for at least 1 hr. Visual motor response (VMR) experiments were run using white light cycles on-off 4 times for 5 min intervals for a total of 40 minutes. All behavioral experiments were recorded between 11 am and 3 pm, with 2-5 independent trials per condition. Larvae were genotyped following behavioral exper..., Programs and software used to acquire and process data; Daniovision behavioral box and Ethovision XT11 software, custom MATLAB scripts and PRISM statistical software (GraphPad inc.).Â