Characterization of in utero valproic acid mouse model of autism by local field potential in the hippocampus and the olfactory bulb

• VPA mice exhibited ASD characters and relatively unaffected physical features.
• VPA mice exhibited distinctive hippocampal LFP while exploring novel open field.
• Disrupted olfactory bulb LFP was found in VPA mice.
• Locomotor-related hippocampal theta oscillation remained intact in VPA mice.
• Hippocampal and olfactory bulb LFP might be surrogate biomarkers of VPA mouse model.

Valproic acid (VPA) mouse model of autism spectrum disorder (ASD) has been characterized mostly by impaired ultrasonic vocalization, poor sociability and increased repetitive self-grooming behavior. However, its neural signaling remained unknown. This study investigated the local field potentials (LFPs) in the dorsal hippocampal CA1 and the olfactory bulb while animals exploring a novel open field. VPA was administered at gestational day 13. The results demonstrated three core features of ASD in male offspring. However, there was no difference in Y-maze performance and locomotor activity. Analysis of hippocampal LFP power revealed significantly increased slow wave (1–4 Hz) and high gamma (80–140 Hz) oscillations and decreased theta (4–12 Hz) activity in VPA mice. In the olfactory bulb, VPA animals showed greater slow wave (1–4 Hz) and beta (25–40 Hz) activity and lower activity of low gamma (55–80 Hz) wave. Regression analysis revealed positive correlations between hippocampal theta power and locomotor speed for both control and VPA-exposed mice. There was no significant difference between groups for modulation index of theta (4–12 Hz) phase modulated gamma (30–200 Hz) amplitude. These findings characterized VPA mouse model with LFP oscillations that might provide better understanding of neural processing in ASD.

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