Chiharu Hidaka, Taiki Kashio, Daiju Uchigaki, Shinichi Mitsui

Both environmental and genetic conditions contribute to the robust development of neuronal circuits and adulthood behaviors. Loss of motopsin gene function causes severe intellectual disability in humans and enhanced social behavior in mice. Furthermore, childhood maltreatment is a risk factor for some psychiatric disorders, and children with disabilities have a higher risk of abuse than healthy children. In this study, we investigated the effects of maternal separation (MS) on adulthood behaviors of motopsin knockout (KO) and wild-type (WT) mice. The MS paradigm decreased the duration that WT mice stayed in the center area of an open field, but not for motopsin KO mice; however, it decreased the novel object recognition index in both genotypes. In the marble burying test, motopsin KO mice buried fewer marbles than WT mice, regardless of the rearing conditions. The MS paradigm slightly increased and reduced open arm entry in the elevated plus maze by WT and motopsin KO mice, respectively. In the three-chamber test, the rate of sniffing the animal cage was increased by the MS paradigm only for motopsin KO mice. After the three-chamber test, motopsin KO mice had fewer cFos-positive cells in the prelimbic cortex, which is involved in emotional response, than WT mice. In the infralimbic cortex, the MS paradigm decreased the number of cFos-positive cells in motopsin KO mice. Our results suggest that motopsin deficiency and childhood adversity independently affect some behaviors, but they may interfere with each other for other behaviors. Defective neuronal circuits in the prefrontal cortex may add to this complexity.