The Domestic Chick as a Model for Studying Early Social Behaviors and Dopaminergic Dysfunctions in Autism and Fragile X Syndrome

The ability to engage in social interactions is essential for survival and adaptation, relying on an intricate interplay of innate orienting mechanisms, motivation, and reinforcement learning. Crucially, early life represents a sensitive window for the emergence of such social abilities, and disruptions in these foundational processes are considered as early manifestations of dysfunctional social development, such as in Autism Spectrum Disorders (ASD). Importantly, among the neuromodulatory systems implicated in social behavior, dopamine (DA) plays a central role, by regulating mechanisms such as social orienting, reward processing, and motivation. In addition, the Dopamine Hypothesis of ASD suggests that early dysfunctions in DA circuits may also critically impair the development of social skills, highlighting the importance of investigating these mechanisms from the earliest stages of life. This thesis explores this framework using the domestic chick, a precocial model that exhibits spontaneous social preferences immediately after hatching and independently from postnatal experiences. Specifically, through an integrated approach combining behavioral assays, immunohistochemistry, molecular analyses, and electrophysiology, this work examines how early neurodevelopmental perturbations shape social behavior and its underlying neurobiological substrates. First, we will describe how embryonic exposure to valproic acid (VPA), a compound known to increase the risk of developing ASD and used in animals to model the disorder, impacts chicks’ early social orienting abilities, motivation, and dopaminergic development. Then, we will present the design and the implementation of a CRISPR-based genetic model of Fragile X Syndrome (FXS) in chicks, targeting FMR1 to establish a novel avian model for studying ASD-related dysfunctions. By bridging behavioral phenotyping with neurobiological analyses, this work aims to offer new insights into the role of DA in early social behaviors and their disruption in NDDs.