Animal models of autism spectrum disorder: Bridging biology to behaviour

Over recent decades, autism spectrum disorder (ASD) diagnoses have increased, at least partly because of improved recognition and awareness. ASD is a highly complex condition, with multiple genetic and environmental factors that can affect several brain functions and circuits. This leads to wide variation between individuals in their characteristics, difficulties, and support needs, highlighting the importance of understanding biological mechanisms and developing interventions that may improve their daily life. Studying autism in humans is challenging because it is a neurodevelopmental condition and brain mechanisms cannot be examined or manipulated under the same controlled conditions used in laboratory research. They allow researchers to study how genes, brain development, environmental exposures, and neural circuits may contribute to ASD. They can also help identify biological mechanisms and assess the safety or potential effects of different therapeutic interventions. Animal models are therefore important, although no single model can reproduce the full spectrum of autism. This review examines the animal models used in ASD research, with particular focus on mice, which remain the most widely used animal model. Mice can be genetically modified relatively easily, their development and behavior are well understood, and many methods are available to study specific genes, cells, and brain circuits. Different behavioral tests have also been developed to examine multiple ASD-related domains. We also consider other animal models, each with distinct biological and behavioral features that make them useful for particular research questions. We compare the strengths and limitations of these models and discuss the criteria used to assess their relevance to ASD in humans. Combining animal research with human studies and non-animal models can improve our understanding of ASD and support the development of safer, more relevant therapeutic strategies aimed at addressing the needs and improving the daily lives of people with autism and their families.