Faces convey a great amount of socially relevant information related to emotional and mental states, identity and intention. Processing of face information is a key mechanism for social and cognitive development, such that newborn babies are already tuned to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. Similar to neonates, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarker of social deficits in autism spectrum disorders (ASD). We used VPA exposure to induce neurodevelopmental changes associated with ASD in domestic chicks and tested whether VPA could impact the expression of the animals’ approach responses to schematic face-like stimuli. We found that VPA impairs the chicks’ preference responses to these social stimuli. Based on the results shown here and on previous studies, we propose the domestic chick as animal model to investigate the biological mechanisms underlying face processing deficits in ASD.

In recent years, the role of the dopaminergic system in the regulation of social behavior is being progressively outlined, and dysfunctions of the dopaminergic system are increasingly associated with neurodevelopmental disorders, including ASD. To further elucidate the role of the dopaminergic system in ASD, we investigated the effects of embryonic exposure to valproic acid (VPA) on the postnatal development of the mesencephalic DA system in the domestic chick. We found that VPA affected the rostro-caudal distribution of DA neurons, without changing the expression levels of several dopaminergic markers in the mesencephalon. We also investigated a potential consequence of this altered DA neuronal distribution in the septum, a social brain area previously associated to social behaviour in several vertebrate species, describing alterations in the expression of genes linked to DA neurotransmission. These findings support the emerging hypothesis of a role of DA dysfunction in ASD pathogenesis. Together with previous studies showing impairments of early social orienting behaviour, these data also support the use of the domestic chick model to investigate the neurobiological mechanisms involved in early ASD symptoms.

One of the most fascinating properties of the human brain is the capacity of newborn babies to recognize and orient to faces and simple schematic face-like patterns since the first hours of life. A striking feature of these social orienting mechanisms is their transversal appearance in remarkably diverse vertebrate species. Similar to newborn babies, also non-human primates and domestic chicks have been shown to express orienting responses to faces and schematic face-like patterns. More importantly, existing studies have hypothesized that early disturbances of these mechanisms represent one of the earliest biomarkers of social deficits in autism spectrum disorders (ASD). Recent data suggest that newborns at high risk for the disorder express altered responses to schematic face-like configurations. Here we modeled ASD in domestic chicks using the anticonvulsant valproic acid (VPA), and tested the animals for their predisposed preference towards schematic face-like configuration stimuli. We found that VPA impairs the chicks' preference responses to the social stimuli. Based on the results shown here and in previous studies, we propose the domestic chicks as elective animal models to study early-emerging neurobehavioural markers and to investigate the biological mechanisms underlying face processing deficits in ASD.

In recent years, the role of the dopaminergic system in the regulation of social behavior is being progressively outlined, and dysfunctions of the dopaminergic system are increasingly associated with neurodevelopmental disorders, including autism spectrum disorder (ASD). To study the role of the dopaminergic (DA) system in an animal model of ASD, we investigated the effects of embryonic exposure to valproic acid (VPA) on the postnatal development of the mesencephalic DA system in the domestic chick. We found that VPA affected the rostro-caudal distribution of DA neurons, without changing the expression levels of several dopaminergic markers in the mesencephalon. We also investigated a potential consequence of this altered DA neuronal distribution in the septum, a social brain area previously associated to social behavior in several vertebrate species, describing alterations in the expression of genes linked to DA neurotransmission. These findings support the emerging hypothesis of a role of DA dysfunction in ASD pathogenesis. Together with previous studies showing impairments of early social orienting behavior, these data also support the use of the domestic chick model to investigate the neurobiological mechanisms potentially involved in early ASD symptoms.

Cerebral asymmetry is a fundamental aspect of brain organization. Abnormal language hemispheric activation and differences in the prevalence of handedness have been observed in individuals with ASD, suggesting atypicality in cerebral structure and lateralization. Zebrafish are increasingly emerging among the key model species to study brain lateralization, with asymmetric development of the epithalamus as a model to investigate the relationship between brain asymmetry and behavior. We exposed zebrafish embryos at 5 hour post-fertilization to one micromolar dosage of valproic acid for 24 and 48 hours, assessed social interaction and visual lateralization in a social task, the mirror test, and measured gene expression changes in the thalamus and the telencephalon. We show that after exposure to valproic acid, zebrafish exhibit social deficits and alterations in lateralized social responses to their own reflected image. Valproic acid also induced changes in the asymmetric gene expression of the thalamic marker kctd12.1/leftover and had a significant effect on the expression of telencephalic genes known to be asymmetrically expressed in adult fish. Our data indicate that one micromolar doses of VPA are sufficient to neutralize both the visual field bias and the asymmetric epithalamic gene expression, opening new perspectives to investigate brain lateralization and its link to ASD in a zebrafish model.