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

Abstract

Predispositions to preferentially orient towards cues associated with social partners, such as face-like stimuli or biological and animate motion, appear to guide social behavior from the onset of life. These predispositions have been documented in several vertebrate species including human neonates, young monkeys and newly-hatched domestic chicks. Human newborns at high familiar risk of Autism Spectrum Disorder (ASD) show a remarkable deficit in their attention toward these predisposed stimuli, either static and dynamic, compared to newborns at low risk. A previous study showed that prenatal exposure to valproic acid (VPA) (that in humans increases the risk of developing ASD) impairs the chicks' predisposition to approach naturalistic social stimuli that convey static configurations of features (a stuffed hen), without impairing general cognitive and learning abilities. Here we investigated the effect of VPA exposure on another class of social predispositions, i.e. the spontaneous preference to approach self-propelled objects, namely objects that display autonomous changes in speed. We observed that the preference for stimuli displaying autonomous changes in speed was impaired in VPA-compared to vehicle-injected chicks. Our results indicate an effect of VPA on the development of predisposed orienting mechanisms towards dynamic stimuli, that could be used to investigate the molecular and neurobiological mechanisms underlying ASD early symptoms.

Newborns’ sensitivity to speed changes as a building block for animacy perception

“…Understanding how our visual system perceives animacy is a mandatory step in understanding how we perceive the social world. The perception of animacy is an automatic process that begins in early infancy, but in some cases this perception develops atypically, leading to difficulties in perceiving animacy, such as in the case of autism spectrum disorders [50, 51] (see some recent studies on an animal model of autism [52]). Therefore, knowing more about the quality of motions that triggers such a fundamental perceptual ability is vital to understanding how our social cognition works in both typical and atypical individuals.…”

A transient time window for early predispositions in newborn chicks

“…The implications of delayed or impaired early predispositions for the physiological development have still to be clarified. Yet, a generalised pattern of absent or delayed predispositions has been already documented both in human neonates at high risk of autism 23 and newborn chicks exposed to autism-inducing drugs 24,25 . The domestic chick appears to be an ideal model for studying early predispositions for several reasons: the study of early predispositions is easy in avian species, whose experience can be manipulated more easily from embryonic development; extensive parallels in early predispositions between neonate chicks and humans have been extensively documented, and our results confirm that early predispositions are widespread among vertebrate species and fixed in the domestic chicken; both physiological and pathological patterns appear to converge in human neonates and chicks in the first hours after birth; our findings point towards a basis of early predispositions that might not depend on visual experience, and whose neurobiological basis has already clarified several target areas in the chick brain such as the lateral septum, thee preoptic area and the nucleus taeniae of the amygdala [37][38][39][40][41] .…”

“…Imprinting can also modulate predisposed responses 17 . While chicks are a convenient model to investigate early predispositions -because they are a precocial 18 species that can be easily tested in the absence of previous visual experience -human babies show striking similarities in the response to the stimuli preferentially attended and approached by chicks ( 6,(10)(11)(12)(19)(20)(21)(22)(23)(24)(25) ).…”

“…Interestingly, both human neonates at high familial risk of autism 23 and chicks exposed to drugs that increase the risk of developing autism in humans 24,25 exhibit an impairment (or a temporal shift) in early predispositions for animacy. This is another piece of evidence that points at a possible conserved origin of early predispositions in vertebrates.…”

Embryonic valproate exposure alters mesencephalic dopaminergic neurons distribution and septal dopaminergic gene expression in domestic chicks

“…VPA is an anticonvulsant known to interfere with development of the social brain, whose prenatal exposure is associated in humans with neural tube malformations, reduced cognitive function and an increased risk for developing ASD (Christensen et al, 2013). VPA embryonic exposure has been extensively used to model ASD core symptoms in diverse animal species (see for a review Bambini-Junior et al, 2014) including the domestic chick, where it induces alterations of several aspects of social behaviour (Nishigori et al, 2013;Sgadò et al, 2018;Lorenzi et al, 2019;Zachar et al, 2019;Adiletta et al, 2021). Here we examined the anatomical and molecular layout of the mesencephalic DA system in domestic chicks exposed to VPA during embryonic development.…”