Spontaneous Visual Preference for Face-Like Stimuli Is Impaired in Newly-Hatched Domestic Chicks Exposed to Valproic Acid During Embryogenesis

Abstract

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.

Keywords: autism spectrum disorder; brain development; face processing; social predispositions; sodium valproate.

FIGURE 1

Schematic illustration of the social preference test apparatus and the stimuli. (A) The chick was placed in the center of the arena and was free to approach either of the stimuli, placed at the two ends of the apparatus and lit by a 201 lumen LED. The chick’s behavior was video-recorded from above. (B) The stimuli consisted of orange stiff paper silhouettes containing internal features resembling a face-like configuration (left) or a non-social control configuration (right). The chick image is courtesy of Openclipart (openclipart.org) under Creative Commons Zero 1.0 Public Domain License.

FIGURE 2

Spontaneous visual preference test. Social preference test for schematic face-like (social) stimulus and non-social stimulus (see “Materials and Methods” for details). Bar graphs represent time spent in the choice sections (A) social preferences indexes (B), latency to first choice (C), and spontaneous alternations (D). (A) Mixed model analysis on the time spent in the three apparatus sections (face, center, and non-face) considering treatment and sex as fixed between subject factors and the time spent in each apparatus section as fixed repeated measures, shows a significant difference in the absolute time spent in the three sections (not shown) and a significant interaction between treatment and time spent in each apparatus section, and no other main effect or interactions between the factors analyzed. Sidak multiple comparison test shows a significant effect of treatment on the time spent in the non-face chamber. (B) Analysis of variance of social preference indexes using treatment and sex as between-subject factors, revealed a significant main effect of treatment and no other main effects or interactions among the factors analyzed. One-sample t-test on preference indexes indicate a significant difference from chance level for the control group, but not for VPA-treated chicks. The number sign (#) indicate significant departures of the preference index from chance level (0.5), marked by the red line. (C) Behavioral activity during the test measured as latency to express a choice. Analysis of variance on time taken by the chicks to move in one of the choice sections using treatment and sex as between-subject factors, showing a significant effect of treatment and no other main effects or interaction. (D) Behavioral activity during the test measured as sections alternations. Analysis of variance on number of alternations between the three sections, using treatment and sex as between-subject factors, showing no significant main effect of treatment or sex, and no interactions. Data represent Mean ± SEM, ^#p < 0.05, ^∗p < 0.05.

FIGURE 3

Social preference index of sex groups. Bar graphs represent social preference indexes for males and females. One-sample t-test on preference indexes indicate a significant difference from chance level for female control animals, but not for males or VPA-treated chicks of both sexes. The number sign (#) indicate significant departures of the preference index from chance level (0.5), marked by the red line. Data represents Mean ± SEM, ^##uncorrected p < 0.01.