Alteration of spontaneous spectral powers and coherences of local field potential in prenatal valproic acid mouse model of autism

Abstract

Previously, autism spectrum disorder (ASD) has been identified mainly by social communication deficits and behavioral symptoms. However, a link between behaviors and learning process in the brain of animal model of autism remained largely unexplored. Particularly, spontaneous neural signaling in learning-related brain areas has not been studied. This study investigated local field potential (LFP) of the hippocampus (HP), the olfactory bulb (OB) and the medial prefrontal cortex (mPFC) in mice prenatally exposed to valproic acid (VPA) on gestational day 13. Adult male Swiss albino mouse offspring implanted with intracranial electrodes were used. VPA-exposed mice exhibited ASD-associated behaviors. Hippocampal LFP analysis revealed that VPA group significantly increased low gamma activity (25–45 Hz) during awake immobility. Regression analyses confirmed positive correlations between locomotor speed and hippocampal theta oscillations in control but not VPA group. VPA group exhibited increases in delta (1–4 Hz) and beta (25–35 Hz) activities in OB during awake immobility and active exploring, respectively. Moreover, significantly increased and decreased coherences between HP and OB of VPA animals were seen within gamma (active exploration) and theta (awake immobility) ranges, respectively. In addition, significant increase in coherence between HP and mPFC was seen within delta range during active exploration. In addition to three ASD symptoms, VPA animals also exhibited differential patterns of olfacto-hippocampal LFP, altered locomotor speed-related hippocampal theta activities and distinct interplays between HP and learning-related brain areas. The altered olfacto-hippocampal and medial prefrontal cortex-hippocampal networks may underlie impairments in autism mouse model.