VPA-induced autism impairs memory ability through disturbing neural oscillatory patterns in offspring rats.

Autism spectrum disorder (ASD) is a general neurodevelopmental disease characterized by unusual social communication and rigid, repetitive behavior patterns. The purpose of this study was to investigate the effects of ASD on the alteration of neural oscillatory patterns and synaptic plasticity, which commonly supported a wide range of basic and higher memory activities. Accordingly, a prenatal valproic acid (VPA) exposure rat model was established for studying autism. The behavioral experiments showed that the social orientation declined and the memory ability was significantly impaired in VPA rats, which was closely associated with the synaptic plasticity deficits. Neural oscillation is the rhythmic neuron-activity, and the pathological characteristics and neurological changes in autism may be peeped at the neural oscillatory analysis. Interestingly, neural oscillatory analysis showed that prenatal VPA exposure reduced the low-frequency power but increased high-frequency gamma (HG) power in the hippocampus CA1 area. Meanwhile, the coherence and synchronization between CA3 and CA1 were abnormally increased in the VPA group, especially in theta and HG rhythms. Furthermore, the cross-frequency coupling strength of theta-LG in the CA1 and CA3 → CA1 pathway was significantly attenuated, but the theta-HG coupling strength was increased. Additionally, prenatal VPA exposure inhibited the expression of SYP and NR2B but enhanced the expression of PSD-95 along with decreased synaptic plasticity. The neural oscillatory patterns in VPA-induced offspring were disturbed with the intensity and direction of neural information flow disordered, which are consistent with the changes in synaptic plasticity, suggesting that the decline in synaptic plasticity is the underlying mechanism.