INVESTIGATION OF CORTICAL NEURAL NETWORK EXCITABILITY EX VIVO IN A RAT MODEL OF AUTISM
Viktor Kelemen1, Kinga Moldován1, Tímea Májer1, Katalin Szádeczky-Kardoss1, Veronika Bódi1, Sándor Borbély1, Attila Szűcs1, Petra Varró1, Ildikó Világi1
1 Department of Physiology and Neurobiology, Institute of Biology, Eötvös Loránd University, Budapest
Autism is a neurodevelopmental condition as diagnosed by behavioral impairments including impaired social interaction, compromised communication and restrictive stereotyped behaviors and interests. Its prevalence is 0.5-1% and autism has been shown to increase the risk of developing epilepsy, so it is important to investigate the background of both diseases. The valproic acid (VPA) rat model is the most commonly used to study autism-like behaviors. VPA is an antiepileptic drug whose prenatal exposure increases the risk of developing autism in offspring. Our studies were conducted on Wistar rats in two age groups: 6 weeks and 3 months. Pregnant rats received an intraperitoneal injection of VPA on the 12.5th day after mating (dose 500 mg/bwkg). Horizontal brain slices were prepared from offspring rats for field potential measurements and parallel detection of intrinsic optical signals. Excitability changes in the entorhinal cortex were investigated in two conditions: spontaneous bursts evoked by magnesium-free solution (MFR) and afterdischarges evoked by brief bursts of high frequency electrical stimulation were investigated. Length of afterdischarges in slices from VPA-treated, 6-week-old male rats was significantly longer than in slices from control animals, suggesting an increase in seizure sensitivity in treated animals. The optical signal showed concordance with the electrophysiological results. In MFR, a slightly different pattern could be observed in VPA-treated rats compared to controls, but burst patterns are highly variable, so increasing the sample numbers would be necessary. Studies on 3-month-old animals are still ongoing. Before drawing final conclusions, further analysis of the data is needed.