Embryonic Exposure to Valproic Acid Impairs Social Predispositions of Newly-Hatched Chicks

Paola Sgadò,Giorgio Vallortigara,Elisabetta Versace,Orsola Rosa-Salva

doi:10.1038/s41598-018-24202-8

Paola Sgadò, Giorgio Vallortigara + Show 2 more

Open Access

https://doi.org/10.1038/s41598-018-24202-8

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Abstract

Biological predispositions to attend to visual cues, such as those associated with face-like stimuli or with biological motion, guide social behavior from the first moments of life and have been documented in human neonates, infant monkeys and domestic chicks. Impairments of social predispositions have been recently reported in neonates at high familial risk of Autism Spectrum Disorder (ASD). Using embryonic exposure to valproic acid (VPA), an anticonvulsant associated to increased risk of developing ASD, we modeled ASD behavioral deficits in domestic chicks. We then assessed their spontaneous social predispositions by comparing approach responses to a stimulus containing a face configuration, a stuffed hen, vs. a scrambled version of it. We found that this social predisposition was abolished in VPA-treated chicks, whereas experience-dependent mechanisms associated with filial imprinting were not affected. Our results suggest a specific effect of VPA on the development of biologically-predisposed social orienting mechanisms, opening new perspectives to investigate the neurobiological mechanisms involved in early ASD symptoms.

Highlights

Autism Spectrum Disorder (ASD) comprises a genetically heterogeneous group of neurodevelopmental disabilities characterized by a wide range of impairments in social behaviors
We found differential activation of the intermediate medial mesopallium (IMM), an associative area involved in imprinting learning[21], in chicks that approached a stuffed hen compared to a control stimulus[16]
To investigate the contribution of social predispositions to atypical social behavior related to ASD, in an animal model that allows for controlled experimental conditions, we delivered valproic acid (VPA) in ovo, in the last week of embryogenesis, and compared the performance of VPA- and vehicle-injected chicks on social predispositions to approach a social stimulus, and on affiliative responses mediated by the learning mechanism of filial imprinting

Summary

Introduction

Autism Spectrum Disorder (ASD) comprises a genetically heterogeneous group of neurodevelopmental disabilities characterized by a wide range of impairments in social behaviors. Measuring visual attention towards face-like stimuli and biological motion cues, impairment in the orienting mechanisms towards these social stimuli was observed in neonates at high-risk for ASD, compared to the typical population. This discovery moves the potential for early ASD assessments to the first moments of life, increasing the interest for models reproducing symptoms that can be assessed soon after birth. To investigate the contribution of social predispositions to atypical social behavior related to ASD, in an animal model that allows for controlled experimental conditions, we delivered VPA in ovo, in the last week of embryogenesis, and compared the performance of VPA- and vehicle-injected chicks on social predispositions to approach a social stimulus (a stuffed hen), and on affiliative responses mediated by the learning mechanism of filial imprinting

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