Impaired Epigenesis of Imprinting Predispositions Causes Autism-like Behavioral Phenotypes in Domestic Chicks

Several environmental chemicals are suspected as risk factors for autism spectrum disorder (ASD), including valproic acid (VPA) and pesticides acting on nicotinic acetylcholine receptor (nAChR) if exposed during pregnancy. However, their target processes in fetal neuro-development are unspecified. We report that VPA effectively suppressed the spontaneous motion of 14-day fetuses, and selectively impaired the imprinting of an artifact object (colored toy) in hatchlings while the predisposed preference to biological motion (BM) remained intact. However, blockade of nAChR (by ketamine, tubocurarine, and imidacloprid, a neonicotinoid insecticide) similarly suppressed the fetal motion, but spared imprinting and impaired BM. The underlying molecular and cellular actions were dissociated between the two sets of chemicals. When hatchlings were trained using merged two point-light animations in different colors, VPA and ketamine similarly inhibited the formation of selective preference for the biological image, indicating common hypoplasia in social attachment formation. Fetal epigenesis of BM predisposition and imprinting memory is critical for neonates adaptive socialization. ### Competing Interest Statement The authors have declared no competing interest.