Embryonic Exposure to Valproic Acid Affects Social Predispositions for Dynamic Cues of Animate Motion in Newly-Hatched Chicks

Abstract

Early predispositions to preferentially orient toward cues associated with social partners have been documented in several vertebrate species including human neonates and domestic chicks. Human newborns at high familiar risk of Autism Spectrum Disorder (ASD) show differences in their attention toward these predisposed stimuli, suggesting potential impairments in the social-orienting mechanisms in ASD. Using embryonic exposure to valproic acid (VPA) we modeled ASD behavioral deficits in domestic chicks. To investigate social predispositions toward animate motion in domestic chicks, we focused on self-propulsion, using two video-animations representing a simple red circle moving at constant speed (speed-constant) or one that was changing its speed (accelerating and decelerating; speed-change). Using a spontaneous choice test for the two stimuli, we compared spontaneous preferences for stimuli that autonomously change speed between VPA- and vehicle-injected chicks. We found that the preference for speed changes was abolished in VPA-injected chicks compared to vehicle-injected controls. These results add to previous findings indicating similar impairments for static social stimuli and suggest a specific effect of VPA on the development of mechanisms that enhance orienting toward animate stimuli. These findings strengthen the hypothesis of an early impairment of predispositions in the early development of ASD. Hence, early predispositions are a potentially useful tool to detect early ASD symptoms in human neonates and to investigate the molecular and neurobiological mechanisms underlying the onset of this neurodevelopmental disorder.

Valproate Exposure in ovo Attenuates the Acquisition of Social Preferences of Young Post-hatch Domestic Chicks

“…In line with this is our observation that another form of early adaptive learning that is devoid of social context (passive avoidance learning) is not attenuated by VPA either (present study). However, at variance with the reports by Sgadò et al (2018) and Lorenzi et al (2019), we did not find significant differences between VPA-treated and control birds in other behavioral tasks relevant to early social preferences: distress calls evoked by isolation (suspended by predator sighting), and approach preference for larger over smaller group of conspecifics (with natural or blurred facial features), at least, in the period between 1 and 9 days of age.…”

“…The existing reports on the early behavioral effects of embryonic VPA treatment of domestic chicks in relation to ASD (Nishigori et al, 2013; Sgadò et al, 2018; Lorenzi et al, 2019) seem to agree upon the point that VPA does not impair filial imprinting. In line with this is our observation that another form of early adaptive learning that is devoid of social context (passive avoidance learning) is not attenuated by VPA either (present study).…”

“…This effect on (socially related) visual predisposition was not accompanied by a similar impairment of filial imprinting, in agreement with the Nishigori study (Nishigori et al, 2013). Recently, Lorenzi et al (2019) showed that innate preference for an object autonomously changing speed over one moving with a constant speed was affected in chicks by embryonic VPA treatment. While it is increasingly evident that domestic chicks might offer a useful and inexpensive alternative model for studies of autism-related social deficits, the aptitude of the model could be further corroborated by a refined analysis of the affected elements behaviors, also extended to a later period of postembryonic maturation.…”

Micromolar Valproic Acid Doses Preserve Survival and Induce Molecular Alterations in Neurodevelopmental Genes in Two Strains of Zebrafish Larvae

“…Mice exposed to prenatal VPA also show cellular and molecular phenotypes in the medial prefrontal cortex [ 11 ], the somatosensory cortex, the amygdala [ 12 ], the brain stem and the cerebellum [ 13 ]. In domestic chicks, VPA has been shown to produce alterations in early social-orienting responses and social interaction [ 7 , 8 , 14 ].…”

Gestational Exposure to Sodium Valproate Disrupts Fasciculation of the Mesotelencephalic Dopaminergic Tract, With a Selective Reduction of Dopaminergic Output From the Ventral Tegmental Area

“…VPA-treated animals also exhibit anxiety, depression-like behavior, and abnormal nociception thresholds (Wu et al, 2017). The validity of embryonic exposure to VPA as a model is not restricted to mammals, as evidenced by recent studies in fish (Baronio et al, 2017;Chen et al, 2018) and birds (Nishigori et al, 2013;Sgadò et al, 2018;Lorenzi et al, 2019;Zachar et al, 2019).…”